IM KSAP � ®
ACP
Endocrinology and Metabolsm
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can olege of hyscias CPAmeri Leading Intel Medce, mprovng Lves � A
1
®
IM KSAP � ®
ACP
Endocrinology and Metabolsm
0
can olege of hyscias CPAmeri Leading Intel Medce, mprovng Lves � A
1
®
Welcome to the Endocrinology and Metabolism Section of MKSAP 17! In these pages, you wll find updated inrmation on disorders of glucose meabolism, disorders of the piutary gl and, dis orders of the adrenal glands, dsodes of the thyoid gland re producive disorders, and calcum and bone dsorders. All of hese topics are uniquely uni quely cused cuse d on the needs of generasts and subspeciaists subspeciaists o o endocinolo and metabolsm. The pubicaton o the 17 1 edition of Medcal Knowledge Sel Assessme Assessment nt Program (MKSAP) represents nearly a haf century of seving as the gold-standard resource r internal medcine medcin e education. t aso marks its evolution into an innovative lean ing system to better meet the changng educational needs and leaning styles of all internists. The core content of MKSAP has been deveoped as in previous edtionsnewly generated, essential inrmation n 1 topc areas of internal medicine created by dozens of leadng generass and subspecialsts subspecialsts and guided by certcation and recer tcation requirements, emergng knowledge in the eld and user feedback. MKSAP 17 aso contans 200 all-new, psy chometricaly valdated and peer-eviewed multipe-choice questons (MCQs) r self assessme assessment nt and stud, stud, including 84 n Endocrinolo and Metabolism MKSAP 7 continues to incude H Value Care VC) recommendations, based on the concept of balancing clinica benet with costs and harms, with w ith links to MCQs that iustate these pincipes In addtion VC Key Points are highlighted in the text. Also hghlghted hghlghted with blue text, are Ho/ cused content and MCQs that directy address the the leaning needs nee ds o internists who work in he hospita setting MKSAP 17 Digital provides access to additiona additiona tools allowing you to cusome your learni ng expeience, including regular tex updates wth practice-changing new inmation and 200 new self assessment questions; questions; a board-style pretest to help help direct your learning and enhanced custom-quz options. And, th MKSAP Complete learners can access 1200 eleconic ashcards r quick review of important concepts or revi ew the updated and enhanced verson o Virtua Dx, an mage-based selfassessment too. As bere MKSAP 17 is optmzed r use on you mobile devices, ith iOS- nd Andoid-based apps allowing you to sync your work between you apps and online account and submit r CME credts and MOC points onlne. onlne. Pease vist us at the MKSAP Resource Ste m ksap.acponine.org) to nd out how we can help you stud ear n CME credit and MOC points, and stay stay up to date. Wether you pefe to use the traditoal print version or take advantage of the features availabe through the digital vesion, we hope you enjoy MKSAP 17 and that that it meets and exceeds exceeds your persona leanng needs. On behalf of the many inernists in ernists who have oered ther ther time and expertse to creae the content r MKSAP 17 and the editorial sta who ork to bring this material to you n the best possible way, we ae honored that you have chosen to use MKSAP 17 and appeciate any feedback about the program you may have P ease ee ee e e to send us any comments o mksap_editors@acponlne.org. Snceely
Philip A Mastes, MD, FACP EditorinChief Seno Physican Edcator Director Cincal Content Development Medcl Educaton Divison American College of Physicians i
Endocrinology and Metabolism
Commiee Cta A. Bs, MD, FAC Sctio Edtor 1 ie Inenl eiine lekhip & ing Inenhip ie fe epmen f nenl eiine ein n Eninl & eblim Wke e Univeiy hl f eine Winn-lem Nh lin Howard H. tz, MD, MAC Assocat Edtor 1 ie Jeen e niue ie iviin f il iney Kimme eil llege Thm Jeen niveiy hilelphi ennylvni ssca Cos, MD linil Eninlgi ibee n Eninl lni ugu elh iheville Vigini rst G Harsto, MD, MPH eil ie Jlin ibee ene ie fe epmen f Inenl eiine ein n Enin & eblim Wke e Univeiy h f eiine Winnlem Nh lin Era B ostoMacAa, MD in eil ie ene Repuive eiine ie ul Wmen' elh ene f Exellene Wke e ene Repuive eiine Wke e h f eiine Wintnlem Nh lin ada C La, MD, MHS2 in fe f eiine iviin f Eninl uke Univeiy ei ene uhm V eil ene uhm Nh lin Sara Maso, MD2 in fe epmen f eiine iviin f Enin eblim n ibee Univeiy f h f eine u l
Sos, MD ie fe f eiine ie enign Thyi gm iviin f Ennl ibee n eblim he Ohi e Univeiy hl f eiine lumbu Ohi
Editor-inChief P A. Mastrs, MD FACP eni hyiin Eu ie linil nen evelpmen mein lege f hyiin hilelphi ennylvni
Director, Clinical Program Development Cta D St, MD, FACP2 mein llege f hyiin hilelphi ennylvni
Endocrinology and Metaboism Reviewers min ingh e bb 1 Jhn K hmbein eene hn 2 iee hen enjmin eile 2 Rih mn my Knikknnn k iegel
Endocrinology and Metabolism Reviewer Representing the American Society for Clinical Pharmacology & Therapeutics in ehey h
Endocrinology and Metabolism ora a ad Hdrcso uin mini/Ei ati d! I nge lini kil n igil gm Marart s ie elemen n Euin gm Bc r, nging Ei ,
,
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ACP Principal Staf Patrick C Ague, MD FACP 2 Senio Vice Pesident, Medical Education Sean McKnney 1 Vice esident edical ducation Magare Wes 1 Diector, Self Assessment d Educational Pogms Becky Kmm dito Kae le1 anage Skills Pgm and Digital Pducts Vaerie A. Dangovetsky 1 Administto Een McDona PhD Senio Sta Edito Megan Zboowski Senio Sta dito Rany Henrickson1 Poduction Administto/Edito Linea Donnarumma 1 Sta dito Susan Gaeoe Sta Edito Jackie Twomey Sta Edito Juia Nawrock Sta dito Kmbey Kes Administtive Coodinato Rosemae Houon Administtive Repesentative 1. Has no relationships wit any entt producng, marketing, resellng, or dstriuig ealt care goods or sevices cosmed by or used o paients 2 as discosed relatiosi(s) i any entiy prodcing, maretig reselling, or distitig alth care goods or serices consmed , or sed on paients
Discosue of Reaionshps wih any enity proucing maketing reseing or istribung heah care goos o services consume b or use on paients Patrick C Ague MD FACP tantship x Royalties U Stock Options/Holdings I - q O x iv
Terence Chan MD Honoia () Pieer A Cohen MD Stock Options/oldings (spouse) Ix & I I z I x Honoaia Benjamin Geiser MD Royalties Consultantship I I Lina A Hershe MD PhD Reseach / x ( ) Honoia Wana C Lake MD MHS Reseach Gants/Contcts Sarah Mayson MD 2 Othe Sub-Investigato o Clinical Studies) Mark D Siege MD FACP Consultantship Jennier Spos MD Consultantship Cynhia D Smith MD FACP Stock Options/oldings ;
Acknowledgments () 17 ' (" 17) : Gaphic ( ) ( ) duction/Systems: ( & ) ( )
Chis Patteson (Senio Achitect), and Scott Hurd (Manager Web Pojects & CMS Sevices). MKSAP 17 Digital: Unde the diecton of Steven Spad,
Vice Pesident, Digital Poducts & Sevce s the digital ve son of MKSAP was deveoped wthin he ACP's Digial Poduc Developmen Depatment led by Brian Sweigad (Diecto). Othe membes of the eam ncuded Dan Baon (Senio Web Applicaton Develope/Achtec, Chs Foest (Seno Software DeveloperDesign Lead), Kara Konenwetter (Seno Web Deveope) Bad od (Senio Web Appicaion Deveoper John McKnight (Senio Web Developer), and Nate Peshall (Seno Web Develope). The College aso wishes to acknowledge that many other pesons, too numeous to mention, have contbuted o the poduction of this pogam. Without their dedicated eots this pogram would not have been possible
MKSAP Resource Site (mksap.acponlineorg) The MKSAP Resource Site (mksap.acponne.og) s a continualy updated sie that povides lnks to MKSAP onlne answe sheets or pnt subscbes; the a est detais on Continuing Medca Educaton (CM and Maintenance of Cetiication (MOC) in the United States, Canada, and Austalia eata and othe new informaton.
ABIM Maintenance of Ceification Check the MKSAP Resouce Site (mksapacponlineog) r the lates nomation on how MKSAP tests can be used to apply to the Ameican Board of Intenal Medicine fr Maintenance of Cetication (MOC points.
Royal College Maintenance of Ceification In Canada, MKSAP is an Acceded Sef Assessment Pogam (Section 3) as dened by the Maintenance of Cetication (MOC) Pogam of The Royal College of Physicans and Sugeons of Canada and approved by the Canadian Sociey o Intenal Medicne on Dece mbe 9,204. Appoval extends om Juy 3,205 until uy 3,208 the Part A sections. Approval extends om Decembe 3,205 o December 3208 f the Pat B Fellows of the Royal College may ean thee credits pe hou f partcipatng in MKSAP unde Secton 3. MKSAP also meets multpe CanMEDS Roles, includ ng that of Medical Expet Communicator, Colaborator Manager, Health Advocate, Schola, and Poessional.
Fo nmation on how to apply MKSAP Continuing Medical Education (CME) credts to the Royal Col lege MOC Pogram, vst the MKSAP Resource Ste at mksap.acponine.org
The Royal Australasian College of Physicians CPD Program In Austaa, MKSAP is a Categoy 3 pogam that may be used by Felows ofThe Roya Austaasian College o Physcians (RACP) to mee mandaoy Contnuing Prossional Development (CPD points.Two CPD ced its ae awaded each of the200 AMA PRA Caegory 1 r available in MKSAP . Moe inmation about usng MKSAP this pupose s available at the MKSAP Resouce Ste at mksap.acponine.og and at www.racp. edu.au. CPD cedits eaned though MKSAP shoud be epoted at the MyCPD site at ww.racp.edu.au/mycpd
Continuing Medical Education The Ameican Colege of Physicans (ACP) is accedited by the Accediation Council Continuing Medical Educaton (ACCME to povide contnuing medica educa ton f physcians. Th ACP dsignats tis nuing matial MKSAP fr a maximum of200 AMA PRA aegoy 1 TM _ Physicians should caim ony the cedit commensuate with the exent o thei partcipaton n the actvity. Up to AMA PRA Caegoy 1 1 ae available om Decembe 3 205, o Decembe 3208, the MKSAP Endocinology and Metabolism secion
Learning Objectives he eanng objectives o MKSAP ae to: • Close gaps between actual cae in you pracice and pefeed standads of cae based on best evdence • Dagnose disease states hat are less common and sometmes ovelooked o conusing • mpove management of comobid conditions that can complicate patent cae • Detemine whn to efe paients sugey o cae by subspecialists • Pass he ABIM Cetication Examnation • Pass the ABIM Maintenance of Ceication Examinaton
Target Audience • General internsts and piay care physicans • Subspecaists who need to emain up-to-date in intenal medicine and in aeas outside of thei own subspeciaty aea V
• Residents preparng r he certfcaton examnaton n internal medcne • Physcans preparng r mantenance of ce1caon in internal medcne (rece1caton)
Earn "Instantaneous" CME Credits Online Prnt subscrbers can enter ther answers onlne to earn nstantaneous Continuing Medical Educaon (CME) cred ts. You can subm your answers usng onlne answer sheets tha are provded at mksapacponneorg, where a record of your MKSAP 7 credis wll be availabe To earn CME credts you need to answer al of the quesons n a test and earn a score of a least 50% correct (number of correc answers dvded by the total number of questions) ake any of the fowng approaches: Use he prnted answer sheet at the back of ths book to record your answers Go to mksapacponlneorg, access the approprate onine answer sheet transcrbe your answers and submt your est r nstantaneous CME creds There s no addional fee fr his service 2 Go to mksapacponlneorg access the approprate onlne answer sheet directly enter your answers and submt your test fr instantaneous CME credits There s no addtonal f fr this servic 3 Pay a $5 processng fee per answer sheet a nd submit the prnted answer sheet at the back of ths book by mail or fax a s nstructed on the answer shee Make sure you calculate your score and fax the answer sheet to 25-35-2799 or mal the a nswer sheet to Member and Customer Servce Amerc an Colege of Physcans 90 N Independence Mal Wes Phladelpha P A 906-52 usng the courtesy enve ope provded in your MKSAP 7 slipcase You wll need your 0-digt order number and 8-dg ACP ID number wh ch are prnted on your packng slp Please allow 4 to 6 weeks or your score report to be emaled back to you Be sure to nclude your emal address for a response
Accredtaton Councl fr Contnung Medca Educaon (ACCME) conrbutors to all ACP contnung medcal education actvites are requred to dsclose a ll relevant financal reatonshps wih any entty producng, mar keng reseling or dsrbung health care goods or services consumed by or used on patents Conribuors are requred to use generc names n the discusson of herapeuic optons and are requred o dentfy any unap proved o labe or nvestgative use of commercal prod ucs or devces Where a trade name is used all avalable trade names fr the same product type are also ncluded. If rade-name products manufctured by companes wh whom contrbutors have relationships are dscussed con rbutors are asked to provide evidencebased ctatons n support of the dscusson The nfrmation s revie wed by the committee responsible fr producng hs text If necessary adjustmens o opcs or contributors' roles n content developmen are made to baance the dscusson Further all readers of this text are asked to evaluate the content r evdence of commercal bias and send any re evant comments o mksap_ediors@acponlneorg so that future decsons abou content and contrbutors can be made n ight of this nfrmaton
Resolution of Conflicts To resolve all conlicts of neres and nfuences of vested nterests the Amercan College of Physicans (ACP) pre cuded members of the content-creaton commtee fom decding on any content ssues that nvolved generc or trade-name producs assocaed with proprietary entes with whch these commtee members had relatonshps In addon conten was based on best evdence and updated clnical care gudelnes when such evdence and guidelnes were avalable Conrbutors dsclosure nor maton can be fund wh the lst of conrbutors names and those of ACP prncipal sa lsted n the begnnng of ths book
Hospita-Based Medicine
you do no have a 0-digi orde r number and 8-dgt ACP ID number or f you need help creang a user name and password to access the MKSAP 7 onne an h mkaacnl mal custserv@acponlineorg
nn sbscbes ve ce s sngs onen h s se to he op etn h bn ihghed n blue Hosp ons ) ee e hsse nn en ius oe oe n one pe nd nds
Disclosure Policy
High Vaue Care Key Points
It s the polcy of the Amercan College of Physicans (ACP) to ensure balance ndependence objecvy and scenc rigor n all of ts educatonal acves To ths end and conssten wth the poices of the ACP and he
Key Pons in the text that relate to igh Value Care con cepts (that s concepts hat discuss balancng clncal benet with coss and harms) are desgnate d by the VC icon (HVC).
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Educational Disclaimer The edtors and pubsher of MKSAP 17 recognze hat he development of new maeral oers many opporunites r error Despe our best efrs, some errors may persst in prnt Dg dosage schedues are we believe accuate and in accordance wth curren stanards. Readers re advsed however o ensure tha he recommended dosages n MKSAP 7 concur wth the nrmaion prove n he product nfrmation maeral Ths is especaly mportan n cases of new nequently use or hghy toxc drugs. Appcaton of the nrmaion n MKSAP 7 remans he professona responsiliy of he practiioner. The prmary purpose of MKSAP 7 s eucaional Inormaton presene as well as publcatons echnol ogies, products and/or servces discusse s intended to nrm subscribers about he knowlege echniques and experences of the conrbutors. A diversiy o pro fessonal opnon exists and he views of he contrbu tors are ther own and no hose of he Amercan College of Physcans ACP). ncluson of any materal n he program does not constue enorsemen or recommen daton by he ACP. The ACP does not warran he safey relability accuracy compleeness or useulness of and dsclaims any and all lably or damages and caims that may resul rom he use of infrmaton pubica ions echnologies producs andor services iscusse n ths program
Pubisher's Information
tronic or mechancal includng photocopy withou he express consen of the American Colege of Physicans. MKSAP 7 s r ndivual use only Only one accoun per subscrpon wll be permied r he purpose of eang Connung Medcal Educaion CM) credits and Manenance of Cercaion (MOC) ponscreis an r oher auhoried uses o KSAP 17
Unauthorized Use of This Book Is Against the Law Unauthored reproucon of hs publcaon s unlaw ful The Amercan Coege of Physcans ACP) prohbis reproducton of hs publcaon or any of s parts in any rm eher fr nvual use or or isribuion. The ACP w consider grantng an indivual permsson o reproduce ony limied porions of hs publicaion r hs or her own excusive use. Send requess in wring to MKSAP' Permissons Amercan College of Physicans 190 N. Indepenence Mall West Phaelpha P A 906-572 or email your request to mksap_edors@acponlineorg MKSAP 7 ISBN: 978--938245-8- ndocrnoogy and Meabolsm) SBN: 978-1-93824525 Prine n the United Saes of Amerca For order nfrmaion in he nied States or Canada call 800-523-546 exension 2600. All other countres cal 215352600 (MF, 9 AM - 5 PM ET). Fax nquiries o 25-35-2799 or emai to custserv@acponneorg.
Copyrgh C 205 American College of Physicians All rghts reserved
Errata
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rrata r MKSAP 17 w be available hrough he MKSAP Resource Sie at mksapacponline.org as new nfrmaion becomes known o he ediors
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Table of Contents
Disorders of Glucose Metaboism Diabetes Meitus............. 1 Screening r Diabetes Meitus .......... 1 Diagnostic Crteria r Diabetes Meitus ........ 1 Cassiicaton of Diabetes Meitus........ 1 Management o Diabetes Meitus ....... 5 Inpatient Management o Hypergycemia ........ 11 Hospitaized Patents wh Diabetes Metus 11 Hospitaized Patents Wthout Dabetes Metus.... 12 Management o Hypogycemia ........ 12 Hypoglycemia in Paiens wih Diabees Meis....................... 12 Hypogycemia in Paients Without Diabetes Meitus............... 13 Acute Compications o Diabetes Metus ....... 1 Diabetic Ketoacdosis and Hypergycemic Hyperosmoar Syndrome .............. 1 Chronic Compications o Dabetes Mitus ......... 16 Cardiovascuar Morbidity.......... 16 Diaetic Retinopathy .................. 17 Diabetic Nephopahy........ 17 Diabetic Neuropahy............ 17 Dabetic Foot Ucers ...... 18 Hypogycemic nawareness ........ 18
Disorders of the Pituitary Gland Hypothaamic and Pituitary Anatomy and Physioo .............. 18 Pituitary Tumors.................. 20 Approach to a Sear Mass ......... 20 Mass Eects o Ptuitary umors........... 21 Treatment o Cinicay Nonunctioning Pituitary Tumors ................. 21 Hypopituitarism ........... 21 Adrenocortcotropic Hormone Deciency (Secondary Corso Deiciency) ...... 22 Thyroid-Stimuating Hormone Deciency.... 23 Gonadotropin Deciency ...... 2 ow omon ny.. 4 Cetra Diabetes nsipidus ....... 2 Panhypopituitarism ................ 25 Pituitary Hormone Excess .............. 25 Hyperproactinemia and Proactinoma ....... 25 Acromegay ................ 27
Gonadotropin-Producing Adenomas ..... . 28 Thyroid-Stimuating HormoneSecreing Tm� ...............................
Excess Antidiureic Hormone Secretion.. 28 Cushing Disease ........ 28
Disorders of the Adrena Gands Adrena Anatomy and Physioogy ............. 29 Adrena Hormone Excess .................. 30 Cushing Syndrome ................... 30 Pheochomocytomas and Paragangiomas. 32 Primary Hyperadoseroism ...... 3 Androgen-Producing Adrena umors .. 36 Adrena nsucency ............. 36 Primary Adrena Faure ....... 36 Adrena uncton During Crtica ness .. 38 Adrena Masses ............ ............. 39 ncidentay Noted Adrena Masses .... 39 Adrenocortica Carcnoma ............ 0
Disorders of the Thyroid Gand Thyroid Anatomy and Physioo .... 0 Evauaton o Thyroid Functon............... 1 unctiona Thyroid Disorders ............. 2 Thyrotoxicosis ................... 2 Thyroid Hormone Deciency .... 5 Drug-Induced Thyroid Dysnction ......6 Thyrod unction and Disease in Pregnancy .... 6 Euthyroid Sick Syndrome....................... 8 Thyroid Emergencies ................ 8 Thyroid Storm .......... 8 Myxedema Coma.................. 9 Structura Disorders o the Thyroid Gand 50 Thyroid Nodues ........ 50 Goiters ................ 51 hyroid Cancer ..... 52
Reproductive Disorders Physoo o emae Reproduction ......... .. 53 Amenohea.................... Ciica Features ........ 5 Evauation o Amenorrhea ........... 55 Hyperandrogenism Syndromes........ 55 Hirsutsm and Poycystic Ovary Syndrome 55 Androgen Abuse n Women ....... 56 ix
Female Infertity......................... 56 Physioo of Mae Reproducton ............... 57 Hypogonaism ............................ 5 Primary Hypogonasm ............... 5 Secondary Hypogonasm ................ 5 Anrogen Deficiency n te Aging Mae ..... 5 Evaation of Mae Hypogonaism ............ 58 Testosterone Repacement erapy............ 58 Anaboc Steroid Abse in Men ................... 60 Mae Infertity..................... 60 Gynecomastia .................... 60
Diagnosis and Causes of Hypercacemia ....... 62 reament of Hypercalcemia ............ 65 Hypocacema ......................... 66 Cinca Features of Hypocacemia ............. 66 Diagnosis an Causes of Hypocacemia ....... 66 reatment of Hypocacemia.................. 66 Metaboic Bone Dsease ........................ 66 Osteopenia and Osteopooss ............... 66 Vtamin D Deciecy ........................ 69 Paget Disease of Bone ................... 0
Bbliography
.............................. 71
Calcium and Bone Dsorders Cacium Homeostasis an Bone Physioo......... 61 Hypecacema.......................... 62 Cinica Features of Hypercacemia ............. 62
X
Self-Assessment Test. .................... .... 73 Index .................................
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Endocrinology and Metabolism High Value Care Recommendations he American Colege o Physician, in collaboration with multiple other organizations, is engaged in a woldwide initative to promote the practice o Hgh Value Care (HVC). he goals o the HVC iniave are to improve health car outcoms by providing cae o proven bne and reducng coss by avoiding unnecessay and even haml inteventions. he intiative comprises several pograms that integrate the impotant concept o halth care value (balancing cnical benet with cots and harms) r a given intervention into a broad range o edu cational mateia to addres the needs o tranee prac ticing physicians and patents HVC content has been integated into MKSAP 17 n severa important ways. MKSAP 17 now includes HVC-identifid key ponts in the text, HVCcused multipe choice qutions and r subscrbers to MKSAP Digital, an HVC custom quiz. From the ex t and quesions, we have gen eated the llowing st o HVC recommendations tha meet the deinition beow o hgh vaue cae and bring us closer to our goal o mproving patient outcome while conserving inite resources Hgh Value Care Recommendation: A recommendation to
choose diagnostic and management tratege patients in specic clinical stuation that baance clinical benet with cot and harms with the goa of improving patien outcomes Below are the High Value Care Recommendation r the Endocinology and Metabolsm section o MKSAP 17. • Lifestyle modications ae a cost-eecive intevention that has been proven to decease th rik o paient with pediabetes deveoping type 2 diabtes by 41 ° to 58%. • he data r the ole and coteeciven o self-mon itoing o bood glucose levels are less clear egimen without multple daily inun injecion and noninun regimens; generally thi should be avoided • For noncriticaly ill paients who are eating, th use o basal and pranda subcutaneous nsun is the preerrd and safet choice r achieving inpaien glycemic con trol; oa agens and noninuin injctable agents do not ha ron a y ay aa in a ing • Iolated adulonet gowth hormon decincy s extremely rare and it clinical signiance i dbated; evaluaion r growh hormone dcency houd b reserved r adults with at least on known pitutar y hor mone decienc
• Micrprolactinoma n aymptomatic patints do not reuir treamnt however urviance i rcom mendd (se tem 6). • the hyroid-simuating hormon vl is ankly abnormal additional valuaion of thyoid nction should b coniderd to determine th xtnt o th dynction meau thyroxin (1) when the thyroid timulatng hormon i elevatd and maur both thyoxn ( and triodohyronin (T) when h thyroid-stimulating hormone i uppreed. • here is no linical indcation r erial meaurement o thyroid antbody ties to dtermin t need r or to guide thrapy except to monitor ridual dieae in paient teated thyroid cancer • Radioactive iodine uptak a maure o odine uptake by the thyrod over 4 hou; it s usd to vaua th caus o hyperthyodim and i not ndicated in patients with nomal or levated thyroidtmulating hormone levels. • n patents with ubcnical hypthyrodism, repeat asemnt o thyrod unction houd b prrmed 6 to 1 weeks ater the nita test as the values wll nomaize n up to 30% of patint • An elevated erum thyoid-simulating hormon lev indcat th dagnois o pimary hypothyroidism; thyoid imaging is not indicated unles thr i conce r a nodul on phyal xamination • The typica patte o uhyrod sick yndom nonthy roidal lln yndrom, or low triiodothyronin T) syn drome i a mildly elvated thyrodstimulating homone ev and ghtly lo thyroxine () and tiiodohyronine leve h patt houd not prompt uthr teting n the hospial. • A pain with uthyoid ick yndome a di charged om th hospital hyoid ncion abnormal ii may prit r evra wk o llowup thyrd nction ets houd not b repated untl 6 week ar dicharge. • A rum thyrodtimulating hormone mauremnt i th intial laboatory t in a patient with a thy roid nodule; i the thyrod-timulating hormone is u, n aumn o yroxin nd triiodothyronine hould b permd and a radio nuclid can shoud b considrd to idntiy "hot or nctioning nodul which have a very low iklihood o malignancy and typically do not equir nneedl aspiration xi
• If the hyoid-simulaing homone eve is high o norma, he adioucide scan s unecessay as i is uikely to revea a ho nodule ad utrasonography s a inexpensive a nd highy efecive mehod sai icaion of magnancy s nonfnconng hyoid nodules. • Measuremen o esoseone eves is no recommended if a paent is having reguar mong eecions does no have e gynecomasia o examaion and has a no mal esicuar examiaion as i is highly uikey that he has estoseone deicienc • Mid chonic asymptomaic gyecomasa i he mae paen does no waran evauatio • 25-Hydoxyviamin D has a reaivey ong hafe of sevea weeks s he best ndicao o whoe body
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viamn D saus ad is he recommeded es viamn D deficieny • A 25-hydoxyvitamin eve beween 30 and 40 ng/mL (7500 nmo/L) is deemed scien bone heah; mos expet goups ecommend sceeng a gups a eas once r evidece of defcency sce US icidence is 0% o 60% of he popuao howeve i shoud not be a seria ecug sceenig es • Teame r ow boe mass n posmenopasal women ivoves isyle modicaio (maximizing weigh beang execise ad avodace o obacco o excessive acoho) and viami D and cacium suppemeaion; he need r pharmacoogic erapy is based o he 0year esimaed racure risk (�0% a majo osteopooic acure o � hip acue)(see em 12) r
Endocrinology and Metabolism
Disorders of Glucose Metabolism Diabetes Mellitus Diabetes meitus is a chronic metaboic dsease characterzed by eevated pasma glucose eves as a consequence of insun decienc, impaired acton o insuin secondary to insun resistance, or a combination o both abnormaities. Prediabetes is dened as elevaed plasma gucose eves beow the dagnos ic critera r dabetes bu above he noma rnge Screening for Dabetes Meltus Patients wh dabetes melits may exhbit classc symptoms (poria, poydpsia poyphagia) or moe con1l, they can be asymptomatic Diabetes screenng may detect an eary asp tomatic phase Curren guideines do no recommend outine screeng r type diabetes as there s no consistent evidence that eary reatment durg he asymptomatic sage prevens progression of the isease Simiar it has no been rmy estab shed that screeing mproves cical oucomes in tpe 2 diabe tes However, microvascuar and macovascar disease can be present at the time o diagnoss of type 2 dabetes, which s incative of ongoing organ damage during the asymptomatc phase Fthermore there is evdence that he micovascular and macrovascar sease associated with tpe 2 diabetes may be reduced wih mproved gucose cont eay in the dsease course and tha treament o predabees may deay he onset o tpe 2 abetes. In 2008, the S Preventive Services Task orce (SPST) recommended screening r ype 2 diabetes y in asymptomaic adus with a sustained bood pressure leve (treated or untreated) greaer han 35/80 mm Hg Updaed SPST dra gudeines om 204 have expanded screenig recommendations to l aduts in primary care settings with risk ctors r the deveopmen of diabetes (Table 1). n contras the American Diabees Associaton (ADA)recommends screening r type 2 abetes based on BM! (�2) with additiona rsk ctors incuding a history o gestaion diabetes or age (�4 years) Diagnostc Critera for Diabetes Meitus Prediabetes and diabetes can be diagnosed based on he ele vated resus fom one o the oowing screenng ests epeated on two separate occasions: sting pasma gucose (PG) 2-hour postprandia gucose during an ora gucose toerance test (OGT) or hemogobin A (Tabe ) A ndom pasma gucose evel greate than or eua to 200 mg/dL ( mmo/) wth cassic hypergycemc sympoms is diagnostic of diabetes and
does not warant repeat measurement he diabetes scree1g ests have sevea advantages and disadvantages o consder PG is cheaper and more eadiy avaiabe in most countries com pared wth hemogobin A' but he reurement oveight stng can be probematic OGT best reects the pathophysio o of diabees by identing postprandia hypergycemia sec onday to panceatic beace deciency; howeve, the test is timentensive Hemogobin A testing is more convenen wih no sting euirement s unaected by acute stess or ilness, and provides an accurate reection o the average pasma glu cose over the previous 3 monhs By contrast hemogobin A testng can mss eary gucose abnormaities, such as postpan dia hypegycemia Another disadvantage is its decreased re ability n he seting o anemia hemogobinopathies, or kidney o iver disease. urthermore condtons that aect the trno ver o erythrocytes, such as anemiashemogobinopathies and pregnanc, can aect the reiabity o hemogobin A c. 1
Cassficaton of Diabetes Meitus Categories cassfication of diabees encompass a range of insun abnormaies incuding absoute or reave nsuin deficiency insuin resistance or a combination of these abno mates (ae ) Insulin Defciency Type 1 Diabetes Mellitus
ype dabetes occurs in the setng o insuin deicienc It accounts r % o diagnosed dabetes cases The underying mechanism is destrucion o insunproducing pancreatic bea cels which can be auommunemedated, idiopahc or acuired Autoimmunemediated ype diabetes meitus can esut om a combination of genetic environmena and autoimmune ctors here s a srong association between pe diabetes and specifc HA antigens One or moe precipitaing evens such as va infecions can trigge the automune process o beta-ce desrucion in geneticay susceptibe persons Autoantibodes (one or more) can be present at the te o diagnosis incudng antbodies o he owing: ise ces gutaic acid decarboxy ase (GAD65) tyrosine phosphatases IA2 and IA2 nsuin and inc transporte autoantibodies Measurements of autoant odies o GA6 an A2 are recommended or inii conr mation as both o these assays are higy automated n addtion autoantbodies to GAD6 persist onger than those to ise ces aer the deveopment of diabetes Autoimmunemedated type diabetes has cassicay been consideed a disease of chden and young thin aduts 1
Dis ord es of Glucose Metabosm
TABLE 1.
Sceenng Gdenes ype 2 Diaetes ets n Asyptoatc Ads
Sceenng citeia
ADA
USPSTF
BMI >25• and at least oe additioa rsk actor:
2008udenes
Physica inactivy
Ssained 135/80 mm g eaed or uteated
Firs-degee reatve wih dabees Highis ace/ehcity (bac, Lao, Native Amerca Asia Amecan, Pacic Isade)
201 dated dra
Deivey of a baby weghg4.1 g (9 b)
Screeng o adus in pimary cae setings wth a east oe of te oowing rs factors for G, IG, o ype 2 dabees mets
istoy o GDM
Age 45 yeas
ypeenso (40/90 mm g o on atihypetesive medcation)
Oveweig or obese
DL choesero <35 mg/dL (090 mmo/L) and/o rgyceide eve250 mg/dL (282 mmo/)
stdegee reaive wt diabetes isto o GDM
Poycysc ovay syndome
istory o poycystc ovay sydrome
emogob A1 57%, GT, or G o pevous tesg
gis ace/etnicy (bac, Amerca dan/ Aasa Nave Asia Amercan, ispanic/Latino and ave awaa/acfic sader)
Oter condions associaed wh ins essace (sevee obesy, acatoss ngicans) sory o CVD
aes age 5 yeas or yoge wh ay o the oter sk actors he sceeg crtea
Additona sceening ctea
A paes age 45 yeas or ode
Additona screening consdeatons
Use o gucococoids o antpsychocs
Sceenng nteas
3yea inervas f ess ae orma Yeay testing i pedabetes (hemogobin A bewee 57% ad 65% G FG) s dagosed
3year inervas f ow-sk ad orma pasma gcose vaues I hghrs ads or those wth ea aboma est vaes yeay tesg may be beeca
"At-risk BMI may be l ower in some ethic groups. ADA= Amerian Diabetes Assoiatio; P= bloo d pressure CVD = ardiovaslar disease GD = gestatioal diabetes melltus IFG = impaired fastig glose; !GT= impaired glose toerae USPSTF US Prevetive Servies Tas Fore Daa from Ameia Diabetes Assoato Classfiaio ad diagnosis o diabetes Se 2
In
Stadards of edial are i Diabetes-2015 Diabetes are 205;38 Sppl :S8-6
IPMD: 2537714]
TABE
Dagnostc Cteia o Daetes ets•
Test
Noa Range
Inceased Risk fo Daetes (Predaetes)
Radom pasma gcose
Diaetes
Cassc ypegycemc symptoms ps a random pasma gucose 200 mg/dL ( 11 mmo/L)
asting pasma gcoseb
00 mg/dL
00125 mg/d
26 mg/d
asma gucose g a 2ou 5-g OG
(56 mmo/L) mg (7.8 mmo/L)
(5669 mmo/ mg (7.8110 mmo/
(0 mmo/) mg
emogob A c
5%
5%6%
65%
(111 mmo/)
OGT= oral glose tolerae test the absee of ypegyemi symptoms, a abormal fastg plasma glose, G, or emoglobi A l sould be ofirmed by repea testig The same test soud be used we repeatig te measremet fo ofirmatio If two differet tests are peormed ad oly oe as abormal eslts, te Ameria Diabetes Assoiatio eommeds epeatig the test wth te abomal esults astig for at leas 8 ours Data from Ameria Dabetes Assoiato () lassifiato ad diagosis of diabetes Diaees ae Ja8 SuppS8-S [PID 774
2
Disorders of Glucose Metab olism
TABLE 3.
Cassain aees Mei s
Isi eicecy• Immune-mediated Type 1 diabetes LADA Rae ms: "stif ma sydome, ati-isl ecepto atibodies Idiopahc (seoegative) Acqred Diseases of te exocrie paceas: paceatis tama/ paceatectomy, neoplasa cysc ibosis, emocomaosis, ibocaclos pancreatopay econs cogenta bella Dgelated Vaco (at poiso) ntaveos pentamdie sli Resisace Type 2 Dabetes b Ketoss poec
I
Ohe Rae ypes Geetic deecs in bea-ce ction (icding six distict MODY sydromes) Geetic defecs in ns actio Edociopaties (acomegay, Cshng syndome gcagooma pheocromocyoma, yperyoidism) d (somatostatioma, adosteooma)
°
Dug-reaed: (gcocoticods tiazdes, �blockes, diazoxde tacolms cyclosporie nacn, HV protease iibitos atypica anipsycotics [cozape, oanzapine]) f Geneic sydomes: Down sydrome9
duce ome iui duig a "hoeymoo phae atig evea week to may moth, athough thi ot a adequate o utaied eect Iu theapy i theee ecommeded du ig the hoeymoo phae to educe the metaboic te o the uctiog beta ce to peeve ay edua fctio a og a poibe Late autoimmue diabete i adut (ADA) peet patiet with autoatibode to paceatc betace atige ad betace detuctio who did ot equie ui iitiay but eveay pogeed to a ui equemet Patiet with autoimmuemediated tpe 1 diabete ae at a iceaed ik to deveop othe autoimmue dieae, uch a thyoiditi ad ceiac dieae mot commo hu, ceeig aocated autoimme deae houd be coideed at the time o diago ad/o the deveopmet o ig ad ymp tom Coeu o the equecy ad eectvee o epeat ceeg aociated autommue dieae acg Idiopathic type 1 diabete ca peet with eative iu i deciecy ad epiodic DKA without evdece autoim muity hee i a tog geetic hitoy o diabete, ad Aia ad Aica acety appea to be a pedipoig cto Acquied tpe 1 diabete ca be caued by dieae aect ig the exocie pacea, iectio o dug Diue dam age to the pacea ad beta ce o impaied iui ecetio with ubequet iu dececy occu thee ceaio KY PNS
• Pediabete ad diabete meitu ca be diagoed baed o the eevated eut om oe o the owig ceeig tet epeated o wo epaate occaio: t ig pama gucoe 2hou potpada gucoe duig a oa gucoe toeace tet, o hemogobi A 10 .
Meauemet o autoatibodie to GAD65 ad IA2 ae ecommeded iitia comatio o autoimmue mediated tpe 1 diabete meiu
Woam sydome (DDMOAD) h (lneee Tne ad PradeWii sydomes; myotonic dystopy)d DIDMOAD = diabetes inspidus, diabetes mellitus optic atophy and deafess; LADA: late autommne daetes in adls MOY= maturty-oset diabetes of the youg. aBet-cell destructon suly ledng to bsolte inslin defcency. Jnsuli resstane wt progressve relatie inslin defieny. More common n nonwhte ptients who present wth dibet ketcdosis bt become nonnsln dependent over tme [mpired inslin ction 1mpired insulin seretion 1mpaied insuln seetion mpaed inslin ation o altered hepati luose metabolsm 9lsl defiiey, immnemediated lnsln defiiey
athough t ca occu at ay age o BMI age. The ntal pres etatio ca age fom modet eevatio i pama gucoe eve to diabetic ketoacidoi (DKA) he tme coue beta ce detucto i ao vaabe, athough it i equety moe apid i chide compaed with adut Upo iitiatio o iui theapy pe 1 diabete, the emag uctioig paceatic beta ce m tempoaiy egai the abiy to po-
Insuin Resistance
Iui eitace i chaacteized by the iabity o the pephea ce to utie iui efectivey, with a compea toy iceae i the amout o iui eceted by the pace atic beta ce i epoe to hypegycemia he pacea exhibit a eative iui dececy whe it caot poduce eough iui to ovecome the hypegycemia Obeit pe dipoe to the deveopmet o iui etace Metabolic Syndrome Metaboic ydome the coeitece o a goup o ik cto that iceae a peo' pobabii the deveopmet o type 2 dabete meiu ad cadiovacua dieae (CD I addto to impaed glucoe metaboim thee cto icude ceta body obeit hypeteio, ad hypeipidea (Table 4) Metaboic ydome iceae the eative ik o deveopig CVD by ood ad diabete by ved athough t i ot cea whethe the combiato o cto aociated with metaboic ydome impat a geate ik tha that atbuta be to each dividua ik cto peet the peece o oe 3
Disorders of Glucose Metabolism ' TABLE 4. HNBI C e he Den n he : e Synme n er Qyng eremen ( mee e 3 e 5 er) Waist circumference•
Men 40 (02 cm)b Women 35 (89 m
FastingTG
?150mg/dl(.7mmo/L)or Drg theapy tageig iceased G
H coeseo
Men <0mg/d(0mmo/L) Women <50 mg/d (13mmo/)o rug therapy targeg deceased L
Bood pssure
Sysoc ?30mm g o astoc ?85mm Hg or
asg gucose
ug erapy for hypetension Boo gcose 100mg/dl (56 mmo/ or ug erapy for increased gucose
AHA= American Hea Associatio; HDL= high-desity lipoprotei choleserol; NLBI Natioa Hea, ug ad Blood Isttte TG triglyceries. oe idivals wth iially elevated wais crcfeece easureets [eg. (men 37-39 i or 94-99 cm) owomen 31-34 i or 79-86 cm)] may still be at rsk for
type 2 diabetes or cardiovascar dsease a will beefit fro ifestyle iteetos. A ower wast circferece of 35 i {89 c) shod be sed fo Asia Aerca e 'A lowe waist circuerece of 1 i (79 c) soud be sed o Asia Aerica woe Data ro rudy SM Cleea JI Daiels SR et a Diagosis ad aageet o the etabolic sydroe: A Aerica eat Associatio/Natioal ea, g ad Blood Istitte Scietifc Stateet Execuive Say Circulatio 200 Oct 25;112(1:235-52. [PMID: 1155]
or moe risk ctors r meabolic syndrome, he Endocrine Sociey recommends a 3-year sceenng inerval he mea bolic syndrome coponens ncluding was circumference sting lipid prole sng plasa glucose, and bood pessue. Calcuation o he 0-yea CVD rsk s ecommended n pesons wih meabolic syndrome o deermie the need r liesyle modcaions and theapeuic ineenions o preve or delay progression o ype 2 diabetes o CVD. The Fraingha Rsk Score and he new Pooled Coho quaion om he American Colege o Cardology/ Ameican Heat Associaion are e quenly used wihn the United States o assess CVD isk. Type 2 Diabetes Mellu Type 2 dietes mellus ous r most (90%95%) dig nosed diabees cases I aecs 0.9 mllion (26.9%) o adus in he nited Staes aged 6 years or olde. Asian Americans Ameican Indans Aaska Naives Hspancs and non Hispanic black persons ae at an ncreased risk deveopng diabees compared wih non-Hispanic whte persons. The etiolo o ype 2 diabees is ikely muctorial here is oen a srong my hisory o ype 2 diabees among rstdegree reaives, although he specic genes esponsible r he glu cose abnormaliies reain unidenied. 4
Insulin esisance om obesiy in he seting o elaive insulin deciency conribues o he developmen o type 2 diabees n he majoriy of paiens. The degree o hyperglyce ia depends on he exten o bea-cell uncion which can decline ove ie. Type 2 diabees geneally has an insidious onse o pro onged asypomaic hyperglycemia. Mos patents do no presen wih he cassc sympos o polydipsia polyphaga o polyuria Paients wih ype 2 diabees may present rst wh macovascular or microvascular changes. Alhough ype 2 dia bees s oen consdered an adul disease, the incidence is inceasing along with obesiy raes n chldren and adolescens Resdual insulin poducion om he beta cels is insu cien o conrol glucose adeuaely, but i is able o suppress lipolysis r most pesons wih ype 2 diabees nde exree meabolic sress, such as an ilness some paiens wih type 2 diabees canno suppress ipolyss and presen wih DK. Keosis-prone paiens wih ype 2 diabees are ore lkey o be ovewegh or obese, mddleaged, mae and o black or Latino ehniciy Insulin use during he ime o eabolic sress can oen resoe he bea cels om he gucose oxicity wih a reurn o de exercise, and oral hypoglycemic agens glucose conrol Prior o switching om insuln o oal heapy, pancreaic beacell uncion shoud be assessed wih sing Cpepide and gcose measureents. Lestye modicaions alone or combned wih herapeu ic inerentions can preven or deay he developmen o ype 2 diabees in high-risk persons. Liestye modicaions are a cos-eective nervention Several randoized conrolled i als provide evidence ha die changes, increased daily exer cise and wegh loss arges o % o 7% can sgncanly decrease he risk o developng ype 2 diabetes in pesons wih prediabees by 41% o 8%. Addional metrmin has been shown o reduce the rsk o diabees in paiens wih prediabe es alhough his eec was not as robust as lesye ineven tons In he seng o impaired gucose olerance, ipaired sng glucose vaues, or hemoglobin A 1 values beween .7% and 6.4%, he DA ecomends consdering ermin prevenon o type 2 diabetes ddiional herapeutc agens such as lipase inhibiors gucosdase inhibiors and hiaolidinediones, have been evaluaed o deay o preven type 2 diabees; however he eeciveness, cos and poenial side eecs mus be consid ered bere impemenaton (Table ). c
KEY POINTS
• iesye modcaions ae a cost-eecve inerenion tha has been proven o decrease he risk o patiens wih pediabetes deveopng ype 2 dabees by 41% to 8% • In high-risk pesons, he Americ an Diabees Associaion recommends considerng memin r prevenion o ype 2 diabees paricularly in paens who are younge than 60 years o age, have a BMI geaer han , o have a hisory o gesaional diabetes.
Disorders of Glucose Metabosm
TABLE 5. Strategies to Pevent o Delay Onset of ype 2 Dabees Melus Iee
Eecveess
Diet and execise
Sustaned weight loss of 7% with a eas 150 mnutes o modeae exercse per wee show o delay oset o diabetes by up o 3 years
Smokig cessatio
Modestly efective as ong as i does o cause weigh gan, but is always ecomeded
Baratric suge
Eecve used mobidly obese persos B >40)
Metomn•
Show to delay onset of dabees by up o 3 yeas
Lipase ihibtors orlistat)
Show to deay onse of dabees by up to 3 years
-Glucosdase hbtos (acarbose, voglibose)
Show o deay ose of diabees by up to 3 years
Thiazoldiedoes troglitazoe, rosigtaone pioglitazone)
Show o deay oset o diabetes by up to 3 years
Isuli ad suli seceagogues sulfonylueas megtides)
Ieecve
ACE inhbtors and agioes ecepto blockes
Ieecve
Esoge-progesn
Modest efec ony
imes daily initially to include sting and 1hour or 2hour postprandia vaues Postprandial hyperglycemia in pregnancy may predict worse feta outcomes and complcations Lifestyle interventions and/or pharmacologic agents should be implemented when gucose goals r gestational diabetes are no met Nutriton requirements r gestational diabetes shoud allow r appropriae maternal weight gain r normal etal growth while obtaning goal glucose values A moderae exercise program is recommended r glycemic control nsuin has tradiionaly been the mainstay of therapy r gestational diabees when glycemic goals are not met with diet and exercise O labe use of metrmn and glyburide in pregnancy has been sudied and there appears to be equiva lence n ecacy with insuln; however longterm safety data are lacking Gestatonal diabetes resolves ater pregnancy r most women however the risk of developing type 2 diabetes is % o 10% after deivery and 3% to 60% in the subsequen 10 to 20 years The ADA recommends diabetes screening r women with a hstory of gesational diabees using standard criteria at 6 to 2 weeks postpatum and every 3 years thereaer KY IN
'Preferred.
Gestational Dabetes Metus
Relative insulin deciency during the ncreased insulin resist ance associated with pregnancy can result in the development of gestational diabetes mellitus. Pregnant women at high risk r developing gestatona diabetes include those om certain racial or ethnic groups (Hispanic/Latino Americans, blacks and Amercan Indians) overweight or obese women women older than 25 years of age and women with a strong miy history of ype 2 diabees An estimated 2% to 10% of pregnant women have gestational diabetes Complications related to gestational diabetes include miscarriage fetal dermities large r gestational age innts macrosomia preeclampsia complications durng labor and delivery ncreased pernatal complicaions and mortality Complication rsk is on a con tinuum with increasing hypergycemia Disagreement exists among consensus groups regarding the denition screening methods and diagnosic criteria r gestational diabetes High-risk pregnant women should be screened r overt diabetes at the initial prenatal vist using criteria r nonpregnan women according to the nternational Association of Diabetes and Pregnancy Study Group (ADPSG and the ADA n the absence of over diabetes at he initial oce visit diabetes screening should occur beween 24 and 28 weeks' gestation Once a diagnosis of gestatonal diabees s made glucose monitoring should be perrmed at least ur
• ifestyle inteventions should be impemented to meet glycemic goals in women with gestationa diabetes however when these are not met nsulin should be initiated For women wth a history of gestational diabetes diabe tes sceenng using standard criteria should occur at 6 to 2 weeks postpartum and evey 3 years thereafter Uncommon Tes of Diabetes Melltus Genetic defects n betacell function a nd insulin acton cause some uncommon rms of diabetes see Table 3) Maturity onset diabetes of the young (MODY) is an autosomal dominant monogenetic defect that afects betacell nction but not insulin action MODY should be suspected n nonobese patients with a strong mily history r diabetes when the onset o diabetes occurs bere 2 years of age in the absence of autoantibodies Genec defects in insulin action cause insu ln resistance with varying degrees of hyperglycemia as seen with congenital lpodystroph Several endocrinopathes can impair insuln action or secreton as a consequence of excess hormone production Conditions such as Cushing syndrome and pheochromocy toma decrease the acion of insulin secondary to excess cortiso and epinephrne respectively he hypokalemia nuce hpeaosteronsm can nibt te seceon o insulin
Management of Diabetes Mellitus The most eective management of d iabetes mellius includes a mutidsciplinary appoach including patient education and support engaging patients in their care and decision making 5
Dsorders of Gucose Metabolism lifestyle modicatons with diet and exercise, reduced caoric intake r overweight and obese patients and pharmacologic therapies when necessary o meet idividualzed glycemic goals (Table 6).
Ptint Educion
Diabetes se management education (DSME) and diabetes sel-management suppor (DSMS) are recommended at the time o diagnosis o prediabetes or diabetes and throughout
TABLE 6. Aean Daee Aa n Reene Opaen Gye Ga A w Daee ell Pana Caary e Heg Peaa Chaae Pae Sae Calay (1-2 h ae ea)• A ,/ Heah Gce• Healthy
Early n dsease corse Few comobdtes Peconcepton Patent pefeence
<0% wot sevee ecent ypoglycema
70-130 mg/d (3.9-2 mmol/L)
<80 mg/d(10.0 mmol/)
(<6% fo seect patents)
e expectancy> 10 years Complex ea issues
Signfican comobidies, ncuding advanced atherosceosis or mcovasca complicaions
<80% witho severe recrren ypogycema
onge dation of dabees equen ypogycema ypogycema unawareness Lie expecancy <10 years Older adlts
ew comorbdes xended fe epectancy No imparmen of cognton or uncon Mltple cmbdtes ypoglycemc sk
<70%-75% wthot sevee ecen hypogycema
90-30 mg/d (5072 mmo/)
<80% whot sevee ecuren hypogycema
90-0 mg/d (5083 mmol/)
<8.% wot sevee recrent hypoglycema
100-180 mg/d (.610.0 mmol/)
<60% wout sevee recuren hypogycemia
6099 mg/d (3355 mmol/L)
00-19 mg/d6 mmo/)
9 mg/d (53 mmo/)
-ho ae mea: 140 mg/dL (78 mmo/
a s Md mparments n cognon and ncon oo eath Chonc comobidties w endsage dsease ongem cae placement Moderaetosevee mpament n cognton and ncon mted fe epectancy Pregnant women
reeistng ype 1 or type diabees
Gesaona dabees
-hos aer meal 0 mg/d 67 mmo/L) a Recommended i gol cn be met without severe recrrent ypogycemi. l sevee recent ypoglycemi is pesent, there s o recommended emoglobin A 1 gol, s modifiction o te ptient's dibetes mellitus egimen to esolve severe ecurrent ypogycemi sold ke precedence Wen severe recent ypoglycemi is esolved, n eogobin A gol cn be cosen nd tretmen decisons cn gi be mde bsed on tt ndividlized emoglobin A gol wtot reqet ypoglycemi Ts cn be consdeed o ptients wit n ey digosis o dibetes mellitus no signiicnt cdiovsculr disese, o nged wit lestye modiictons o meomin Data om American Diabetes Association. Glycemc targes S ec 6 I Sadars of Meical Care n Diabetes-2015 Diabetes Cae 2015;38(5upl 1):533540 [PMID 25537705 (Moikaton of Tabe 62 537) Data from Aerican Diaetes Association Ole auts Se 10 I Stanars of Meical Care in Diabetes015 Diabees Cae 201538(5ul 56759 [MID 2557711] (Mifi l 101 56
Dt o Aeicn Dibetes Asocition Mngeent o dibetes in pegnncy Sec 12 In Stndrds o Medicl Ce in Dibetes-2015 Dibetes Ce 205;38(Sppl 1 ): 577-579 [MID 2553773J
6
Disorders of Glucose Metabolism
the lifetime of the patient. DSMS is an individualized plan that provides opportunities r educational and motivational support r diabetes self management. DSME and DSMS jointly provide an opporunity r colaboration beween the patient and health care providers to assess educaiona needs and abiliies, develop personal treatment goas learn self management skills and provide ongoing psychosocal and clinical support Improved outcomes and reduced costs have been associated with DSME and DSMS. Sel Monitoring of Blood Glucose Blood glucose monitoring can involve a varety of modalies including sel monitoring of bood glucose (SMBG) hemo globin A , or continuous gucose monioring CGM). SMBG is recommended r patents on muliple daily injection (MDI) insulin therapy or continuous subcutaneous insulin inusion (CSII) therap. SMBG should be perrmed fequently during several critical time periods: preprandial bedtime bere and after exercise periods of symptomatic hypoglycemia or hyperglycemia and bere important activi ies such as operating dangerous machnery. Monitoring blood glucose levels 1 to 2 hours after od consumption (postprandial) can be useful to assess prandial nsulin cover age in patients with at-goal preprandial readings but with hemoglobin A 1e not at goal. Overnight blood glucose monitor ing can help detect hypoglycemia or dawn phenomenon. Success with SMBG requires the physician and patient to act upon the inrmation that it provides This can include insu lin dose adjustments changes in meal conent or changes in activity level to reach individualized glycemc goals. The data r the role and cost-eectiveness of SMBG are less clear r regimens without multiple daily insuin injections and non insulin regimens. It is often necessary to combine both SMBG and hemo globin A 1 to determine if adequate control of glucose has been achieved. There is a strong correlaton between hemoglobin A and the average 3-month plasma gucose value. Therere the ADA and the American Association r Clinical Chemistry advocae reporting boh the hemoglobin A and the estimated plasma glucose levels (Table 7) Hemoglobin A monitoring should be measured a the time of diagnosis and every 3 monhs while making changes to achieve glycemic goals. Testing intervas can be decreased to twice yearly after glyce mic goas have been met. CGM technolo measures rea-time glucose values om the interstiial uid evey ew seconds through the emporary placement of a sensor subcutaneously r 3 to days. The sen sor is conneced to a transmitter that sends the data through wireess radiorequency to a dsplay device CGM glucose val ues average + /- 15% om a laboratory glucose measurement. CGM may be useful in persons with equent hypoglycemia hypoglycemic unawareness or extreme uctuations in glu cose levels. CGM sysems can rapidly denti hypo- or hyper glycemia that is not always detected with SMBG or hemoglobin A measuremens Additionally the ADA endorses the use of e
TABLE 7. Comparison of Hemogob A 1 c Value and Estmated Plasma Gose evel Hemoglo A 1 (%)
stmated Aeage lasma ose Leel mg/d(mmo/L)
6
60
486
8
80
9
8
0
40.4
6949
986
Adapted wih permisson of Aercan Dabetes Assiaion, from Translang e A C assay no esmae average guose vaes. Naan DM Kenen J Brg R,
Zhng H, Shofld D RJ; A1(-driv avag gluco stdy goup. !atm Dab Ca 200932 ):207. Dabt Ca. 008 8)1476 IPMD 185006
CGM combined with intensive insulin herapy in aduts years of age) with type 1 diabetes as a successul modality to ower hemoglobin A e levels The greatest improvements in glycemc control are associated with longer periods of CGM use. In patients usng a CGM system it is imporant to note hat it does not replace SMBG. Calibration with SMBG is required a least twice daily with CGM systems. All CGM glu cose values that warrant an mmediate intervention should be conirmed with SMBG pror to action due to a lag time ranging om to minutes r seveal CGM brands between capillary blood glucose and interstitial glucose. Rapid glucose uctua tions further increase the lag time. KEY POINTS
• Blood glucose monitoring including sel monitoring of blood glucose levels hemoglobin A 1c levels or coninu ous glucose monitoring is recommended r patients with diabees mellius requiring multiple daily insulin injections or continuous intravenous insulin injecion therap • The data r he role and costeectiveness of selfmonioring of blood glucose levels are less clear r regimens withou t multiple daily insulin injecions and noninsulin regimens; generally his should be avoided
V
Nonpharmacoogic Approaches Nonpharmacologic approaches to diabetes management should be implemented throughout the lifespan of he paient These approaches can be used alone or as adunct therapy tp dibts to mro th sss t o pharmacologic agents. Medical nutrition therapy and exer cise can be used in conjunction with insulin therapy r patients with ype dabetes. Medical nutrition therapy is an essential component of any successl management plan r paients wi th prediabetes or diabees. Modest weight loss 0- 8.0 kg [.-1. lb] or %) 7
Disorders of Glucose Metaboism
through caoric reduction can beneft some overweight or obese adults with type 2 diabetes. Consistent exercise provides beneficia efects on gucose contro, weight and cardiovascuar status Fo persons with diabetes in whom no contraindcatons exst, aeobic exercise shoud consist of at eas 150 minues/week at a moderae intensity eve, 75 minutes/week at a vigorous acivty eve or a combination of hese two Resistance training shoud be incorporated into the execise routine at east 2 days pe week Hypogycemia and extreme hypegycemia can worsen i pe sent at the time of exercise and shoud be coected bere proceeding with inceased physica acivit Bariatric surgica procedures (restrictive and bypass) can be consideed in obese atiens with type 2 dabetes Wegh oss and dabetes remission rates are significant with these pocedures but the ong-tem benefits require additona studies See MKSAP 17 Gastroenteogy and Hepatoo and MKSAP 17 Genera Inerna Medicine r more inrmaton Depession anxiety and diabetesreated stress are com mon among patients with diabetes and may impai their abi ity to acheve success wih a diabetes management pan Sceening shoud occur continuousy during the course of diabees treatmen
Pharmacologc Therapy An individuaized treatment goa wi hep guide the seection of he opima treatment regimen For many persons with diabetes a reasonabe goa r hemogobin A 1 is ess than 70% (o ess than 65% f this can be achieved without signicant hypogycemia) If severe recurrent hypogycemia is present, there is no recommended hemogobin A goa as modifca tion of the patien's diabetes egimen to resove severe recur rent hypogycemia shoud take pecedence The increased risks of hypogycemia outwegh the risks of diabetes compica tions in ode patients with onger disease duation which necessiates consideaon of a essstringent gycemic goa The recommended goas om the ADA r bood gucose and hemogobin A e eves are ocated in Tabe 6 e
e
Thepy for Type 1 Diabetes Mellitu Lifeong nsuin herapy is he fistne treatment r type 1 diabetes Physioogic insuin therapy, aso known as ntensive insuin therapy is the dea nsuin regimen as attempts to mimic the actions o noma pancreatic beta ces Inensive insuin therapy incudes mutpe daiy injections (MDI) 3 y r basa coverage and mutipe pepranda inecions through out the day wih anaogue o reguar insuin Inensive insu in herapy can aso incude contnuous subcutaneous insu n nfusion (CS!) and mea-tme bouses with an insuin pump Data suppot tageting norma gycemc eves with a goa hemogobin A of ess than 7% r most pesons with tye diabetes to reduce ong-term compicaions Long term physioogc insuin thea py reduces eary microvascuar dsease by 4% o 76 and reduces cardiovascuar events by c
8
2% to 57% Inensive insuin therapy has riss ncuding signifcant increases in hypogycemia and weight gain Therapy shoud therere be ndivduay taiored r each patients preferences ifestye, educaton eve fnanca resources, and comorbdites. Avaiabe insuin preparations and their acvity profes are ndicated in Table 8 Most persons with type diabetes are sensitive o the eects of exogenous insuin therap wth in ta tota day doses of insuin typicay anging om 0 to U/kg/d A basa insuin dose shoud account r haf of the tota daiy dose of nsuin whie the remaining nsuin shoud be divided o cove the number of meas consumed during the da. Basa insuin coverage can be provided with one to two daiy inections of insuin detemir gagne or neura prota mine Hagedorn (NPH) insuin CSII can aso provde basa coverage with anaogue insuin For prandia coverage, ana ogue or reguar insuin is njected pror to mea consumption or anaogue insuin is boused wih CSII pior t o meas. Insun dosng immediatey afte a mea is appropiate in certain situ ations particuary when od intake is unpredictabe Postprandia insuin dosing aows r a reducti on in the insu in dose hat is commensurate with the amount of od ingesed o avoid hypogycemia that cou d have resuted from the u insuin dose Fo exampe, the postprandia nsuin dose s reduced by 50% i ony haf o f the mea s consumed
TABLE 8. Phamakne Ppeies Insi n Ps• nsn ye
Onse
Pea
an
90
0
0
0
b
<
0+
00
0
0
0
00
0
0 d
0
00
0
00
00
d
0
0 0
00
0
NPA = neutal potamne aspa; NPH netl potme gedon NPL netrl protmine lspo. The tme cose of eac sn varies sgnfcntly between pesons d wthn the sme peson on dferet das. Terefoe, the tme peods sted sod e cosideed genera gdenes oly Bot isin detemr ad sun grgie c prodce a pek effect in some per sos especia at hger doses he dton of co fo nsln detem vaes depend g on the dose gve Pemxed nslns contanng lage popoo o apd- o shocg nsl ted to ave lge peas occng t n ee tme thn mxtes cotnng smalle poptons o apd ad sotactg nsln
Disorders of Glucose Metaboism
Regular insulin requires a longer time interal between prandial injection and od consumption compared with ana logue insulin due to its longer onset of acton. Classic carbohy drate counting with prandial analogue insulin allows lexbility and variety in the types and sizes of meas consumed by adjusting the dose based on the number of carbohydrates ingested. Typicall, 1 U of analogue insulin is used to cover every 10 to 20 g of carohydrate in the meal. Modified carbo hydrate counting r patients who are unwllng or cannot count carbohydrates includes fixed prandal doses o egular or analogue insulin that can be adjusted by 50% based upon the size of the meal: reguar (100% dose) smal (50% dose) or large (150% dose). In the setting of pre-meal hyperglycemia, the prandia dose of insulin determined by the classic or modified carbohydrate countng methods can be combined with a supplemental insulin dose to correct the hyperglyce mia There are a variety of methods to determine the supple mental insulin dose needed r correction; howeve an additiona 1 U of analogue or regular insulin r evey SO mg/d (2.8 mmo/) above the target blood glucose at the pre-meal measurement is a reasonable starting point. For example an additional 2 U of regular or analogue insulin would be admin istered r a patient with a blood gucose leve o 210 mg/dL (117 mmol/L) if the target blood glucose is 150 mg/dL (8.3 mmol/L) or less. When adminstering any pandial or sup plemental insulin doses the duraton of action of previous analogue or regular insulin inectons must be considered, as the risk of insulin-stacking and subsequent hypoglycemia ncreases if the dosing is too fequent Allowing at least 3 to 4 hours between injectons can decease ths sk. Premixed insulins containing a fixed percentage of a long-acting and regular or analogue insuin are given twice daily, paticularly in patients who are unable to comply with more fequent daily injections, although greater glycemic variability and hypogly cemia are concerns when utilzing a nonphysiologic regimen CII should be considered r select patients with ype 1 diabetes if adequate glycemic control is not achieved with adherence to MD therapy CII may be benecial in several scenaros, including signicant early mornng hyperglycemia ("dawn phenomenon), abie plasma gucose values and e quent DKA fequent severe hypogycema o hypoglycemic unawareness preconception and pregnancy or active life syles/patent preference. If a patient is not adherent with insulin injections and lood glucose monitoring, adheence is unlikely to increase because a pump is prescribed; theere pump therapy is not recommended in the nonadherent patient. Cost of the insulin regimen chosen should be weighed against potental benets MDI regimens equire more insulin supples and glucose monitoring Insulin analogues demon state ewe hypoglycemic events, but cost moe than regula human nsuln Insulin pens ncease both convenence and cost when compared with insulin n vials. Insulin pump sup plies are expensive compared with other nsulin therapies however, data om several analyses indicate that overall CII is a cost-efective treatment modalit
KEY POINTS
• ifelong insulin therapy is the st-line treatment r type 1 diabetes; physiologic insulin therapy reduces ealy microvascular dsease by 34% to 76% in patients with type 1 diabetes mellitus compared wth nonphysi ologic egimens Contnuous subcutaneous nsuin inuson is a cost eectve treatment modalty and should be considered r select patients wth ype 1 dabetes meltus ade quate glycemc contol is not acheved with adheence to multpe daily inection theap
Therapy for Type 2 Diabetes Mellitus Lifesle modifications must often be combined with oral pharmacologic agents r optimal glycemic control particu larly as type 2 diabetes pogresses with continued loss of pan creatc beta-cell function and insulin production Multiple oral agents may be requied or used in conunction with nonnsu ln injectable agents or nsulin as glycemc control worsens. Thee are many options r oal agents with major dierences in cost tming of administation mechanism of action and sideefect profiles (Table 9). Metrmin is the recommended rst-line therapy to be initiated either in conjuncton wth ifestyle modifications at the time of diagnosis or wthin 6 weeks of ling to obtain gycemic control wth lifestyle changes alone Metrmin has a lower incidence of hypoglycemia and weight gain compaed with some of the other oal agents and insulin. Gastointestinal side eects (such as abdominal cramping or diarrhea) ae common with metrmin initial low doses with gradual increases and administraton of the tabet llowing a substan tial meal can improve tolerance to the medication Due to the potential risk of lactic acidosis, contraindications to met rmin therapy nclude serum ceatinine geater than 1. 5 mg/ dL (133 µmol/L) in men and 1.4 mg/dL (124 mol/) in women symptomatic heat iure or liver disease and ilness with hemodynamic instabily Metrmin must be withheld r 48 hours in the setting of intavenous contrast dye. In a non hospitaized patient, metrin should be wthhed wth any illness that may cause dehydation. If lfestyle modications and maximally tolerated doses of metrmin to adequatey control glucose, additional agents should be added every 3 months untl glycemic goals have been met Without strong comparatve-efectiveness data to identify the best class of second-line drugs to be implemented several ctors must be considered. Patient peferences and financial resources are key components to developing an indivdualized treatment plan Another impotant determining ctor in selection o the second-line drug class is the patient's weight. Weightneuta drug casses include -glucosidase inhibitos and dipeptidyl peptidase-4 (DPP-4) inhbitors If weight loss is a desied eect, gluca gon-like peptide 1 (GLP-1) mimetics, pamlintide, and sodium-glucose transporte-2 (GT2) inhibitors are 9
Disorders o Gucose Metaboism
TABE 9.
Phg Agnts Us t Lw B s Lvs Typ 2 ts ts
Clss
ns Atin
Et n Wigt
Risks n Cnrns
ng-r Sts n finit Ots
Insuln•
Decreases hepatic gucose prodtion, ncreases perphera gucose uptake
Increase
Hypogycemia nsuin aegy (rae)
Decrease in both mcrovascua and macrovascuar events
Sonylureas (tobutamide, chorpropamide, gipizide, gyburide, glcaide, glmepide) b
Stimuate nsln secretion
ncrease
Hypogycemia (especally in drugs with ong haflives o in oder popuations); weght gan
Decrease in mcrovascua events bt possibe ncrease in macrovascuar events with tobutamide, chopropamide, gybde, and gpizde not seen with giclazide or gimeprde
Bguanides (metfomn)
Decease hepatic glcose prodon, ncrease nsin mediated ptake of gucose in musces
Neuta
Darrhea and abdomina dscomfot actic acdoss (rare); containdcated n presence of pogressive lver, dney or cadac faie
Decease n both mcrovascua and macrovascular events
-Gcosdase nhibitors (acabose, migto, voglibose)
nhibit poysaccharde absoption
Neutra
Fatuence; abdominal discomfort
ay reduce CVD events
Thiazoidnedones (osigitazone, piogitaone)
ncease peiphea ptake of gucose, decrease hepatic glcose prodcton
ncrease
uid retention heart alre macua edema; osteopoosis (possible increased rsk of bladder cancer with pioglitaone)
Uncear whether piogitazone cases net harm o good
Megltinides (epaglnde, nateglnide)
Stimuate nsin reease
Increase
Hypoglycemia
None
Amyinommetcs (pramitide)•
Sow gastic emptying, sppress glucagon secretion, increase satety
Decrease
Nausea; vomiting; ncreased hypogycemic risk with insin
None
GLP1 mimetcs (exenatide and iragltide"
Sow gastrc emptyng, sppess glcagon seceton increase satey
ecease
Hypogycema when used n comnation with sufonylureas; nasea and vomtng; possbe nceased ris o panceatits and chronic idney disease
None
DPP-4 inhibtos (stagiptn, saxaglptn, vldagiptin, inaglptin, aogiptin)
Sow gastic emptying, suppess gucagon secretion
Neuta
ypogycemia when sed in combination wth suonylureas nausea increased isk of infectons possibe increased risk of pancreatitis
No ncrease in ischemc cardiovascuar events inceased ate of hospitaization for heart faiure with saxagiptin
SGL2 inhibtors (dapagilozn and canagllon)
Increases kidney excretion of gucose
Decease
Hypoglycema wth insuin secretagoges and nslin hypotension kidney mpament; hypesenstvty reactons; nceased canddal gental nfectons nd ir tt inecons
None
CVD = cardovasular sas; DP-4 peptyl peptdas GL1 = guagolk pept ST2 = somluose otraspoe 2 lnjectio. bQr
10
Disordes of Glucose Metaboism
ndidtes to onsider. Weigt gin is likely wt te use of insulin, sulnylures, tizolidinediones nd megtindes. Te risk of yogycemi must be considered wit the selection of ny tereutic gent rtiulrly wen it is combined wit insulin secretgogues or insun. Gstrointestinl side eets rom G mimetics nd rmlnide my decrese tolerbility r some tients nd sould not be used in tients wit gstrresis. tiens wi requent ndidl gentl infetons would not be idel ndidtes r SGT2 inhibitor ter Insulin tery sould be strongy onsidered in te set ing of symtomti hyerglycemi or mrkedly eevted emoglobin (>8.5% to 9%) t te time of dignosis or wen lifestyle moditions nd/or noninsulin teries to cieve glyemi gols. Te merin Assocition of Clinil Endorinologists (CE) recommends weigtbsed initition of bs insulin t intil doses of 01 to 0.3 U/kg. Te dose sould be incresed severl units every 2 to 3 dys to re sting lsm gluose gos bsed on te tient's SMBG redings. Reductons of insulin doses by 10% to 40% sould be mde in the seting of yogyemi wit insulin titrtions If glyemic gols re not met wt bsl nsulin ten rndi insulin sould be dded to te regmen wt equent titrtion o doses r otiml gluose control. Wen remel gluose vlues re not t tientsei gol t e reeding rndil insulin dose sould be inresed or deresed by 10% to 20% n te setting of yer or yoglyemi resetively. (lso see section on Tery r Tye 1 Dibetes Mellitus) KEY POINTS
• For tents wit tye 2 dibetes mellits metormin is recommended rstline tery nd sould be initited n onuntion wit liestyle modtions; it hs lower incidene of yoglycemi nd weigt gin om red wit some of te oter orl gents nd insulin • In oder tients wit tye 2 dibees mellis of longer disese durtion, tretment of severe reurrent yo gyemi sould tke reedene over contrlling emogobin vlues; te inresed risks of yogly cemi outweig te risks of dibetes omlictions.
C Inpat ient Management of Hyperglycemia
Ipaen hyeglycema deed as cossey eevaed pasma gucose vaues above 10 mgd (78 mmoL s asso aed wh poo oucomes Atemps o deease mobd ad moay wth ght gycemc cono (8010 mg/d [. 6 mo/]) have ot conssety demosated mpove mes dverse oucomes d n some segs have shown ceased tes o severe ypogycemc eves ad moay As a esult evsed intent glycemc ages ae ess stnget ha outpent glucose ges o vod boh hypogycemi
ad sevee hypegyema ha ca ead o voume depleo ad eeoye abomaes Hospitalized Patients with Diabetes Mellitus Cay paes wth ype dabees meus w eue su hepy upo admsso o he hosp. o ctcaly paes wh ype dabees aveous su uson heapy shoud be aed whe pasma gucose eves exceed 80 o 00 m dL (0. mmo/) lucose goas o nave ous su ae 40 o 00 mg/d (7 8.1 mmo/L) wth euen bedsde poo ae (POC) moog every 1 o hous su adusmes oay paens he ADA ad AAC advoae a pemea guose goa o ess ha 40 mg/ (7.8 mmo/) a andom pasma guose vaues ess ha 80 mg/L (0 mmo) Theapy adjusmets shoud be osdeed whe pasma guose eves e ess ha 100 mg/dL (5.6 mmo/L) and ae ecessay when guose vaues l beow 70 mg /d (9 mmo/L) to avod oued hyogycema In cos he Amea Coege o hyscas (AC) ecommeds voding gluose eves ess ha 0 mg/d (78 mmo/L) owng o he eased s o hypogyema wh ge glycem o sul s he peed heapy ad ey he sas choice aheg pae gycemc coo. se of sdg scale su aoe s o eommeded as s no physoogc ad euely causes age gucose uctuos owng o the nhee eave atue o s dosg coupled wh the nea unvesa ag ime bewee measueme o glucose d je co o su ha ocus mos hospas Te ecommeded isun egime shoud coorae both basa nd padaJ oveage he seg o pepada ypegycema paa oveage a be suppemeed wih ddiona nsu (oeco o sul) Pand coverge shoud accout he abohdaes cosumed a each meal ad be adjusted acodgly POC gucose motong should cocde wh sui admsao bee meas and at bedme wih ovegh measuemes o moo hypoglycemia ony f sig eadgs ae eevaed o he paient s symomaic. his gucose moog egme w smuate he aents home ue ae dschage. OC moog shoud ou evey 6 hous whe a pae s on su hepy ad eceves ohg y mouh. Oupaen CS heapy can be oued he paet s physa ad meay abe o saey adminse his theray ude pope supevson om ealth cae ovdes wit CS!I epeise OC guose moong basa raes o nsul nd aeniaed bous amouts of sui should be documeed n he medca ecod Oa ages ad osun njecble agents do o have saty o eacy daa he hospta seg he saes ecom mendaon s o dscoue hese agets upon admsson o he hospa. hough couao c be consdeed i a sabe paien wh gyemc coo gol and o nticed cages nuton o hemodyam sttus. These gents cn be paticury dageous stg sates o when ogan peusion or 1
Disorders of Glucose Metabolsm
r, !'uncton s compomsed Resuption o these medicaons Li may b cosdeed oce a paten s sable w egula acivtes CONT. ad nrition o a te time o ospial discarge. C KEY POINTS
C
• F y e e 2 ee e, e ey e e e ge ee eee 180 200 g/L 10111 /L; ge g e e 140 200 g/d 8111 /L eqe ese e g eey 1 2 • y e, d eo s e eee e e eg e gye ges o jee ge o e e e ey e o eg Hospitalized Patients Without Diabetes Melitus Hypergycemia as a reslt of acte stess rlae o iless cocomia edicaios or entel/paenea nuio ca ccur i paets wiout a pevous istory of glcose abo males. The glyceic goas and glcosemaageme stateies i hs popuaio soud low ose hospaled aens wt diabees. ypegycema i hospialzd patints may also indicate the presece of prevousy undagnosed dabetes Maseme o heoglobi A n hypergyceic onhospialize paiens i asibe can provide isgh ino he lgth o he hypeglycemia A hemogob A level a han 65% sggss logsanding hypegl yceia olowup diabetes sceeng ad care shold be implemeed afer discage fom he hospial. 1
1c
Management of Hypoglycemia Hypogycemia in Patients with Diabetes Mellitus Hypoglycemia s a como complcao of intesiv eraetic regies in paes wi dabees elitus ofe limi ig he abiliy o saey reach gycic goas or may patients. voidace o ypoglycemia pror to focsig o a patients heoglobi A goal is o tmos impoance because of h sigiica mobdity and oaliy assocaed wth low pasa gucose eves. Hypoglycema is deined as a plasa gucose lv ess m U e gcos eve lls bow 0 g ( mo ypearnrgic sypos beg o al e paie o yoycemia ogh an incease n heart e seag remos nge ad aniety when gcos evels declie ypcall y he body espods to ypoglycemia by seceing o neegulaory hormoes sch as glago epiepine nopephri cotsol ad grow hooe n successio based on the escaag degree o hypogl ycemia. l he co erregla oy measres ai o he hyogycema is no 1
12
coected cogitve funco begins o dece ad ca be apidy lowed by loss o consciosness seies and deah. Relaive hypoglycema occus wen a paiet as symptoms of yogycea but e pasma glucose leve s geae ha 70 mg/d (39 mmol/). Ths ca ocu wi apd decreases n gcose or wh corecto of glucose to earnoma gycemc eves a paien wi a hstory o polonged hypegycemia (plasma gucose >00 m g/d [. mmo/]) Reatve hypoglycema ca b dminshed i glcose levels ae mainained closer o nomal anges and eatmet o goal gucose evel is acheved over a longer perod o e patients wh a hsoy o polonged unco olled diabes. The etioogy of ypoglycemia can be ite variable Exercise ca lead o hypoglycemia appropae measues are o ake o avod i. Po to execse consumpto of a snac wih 5 to 30 g o caboydraes can help edce the rsk of ypogyceia o a patient ca educe he ose of prndia isn gve at he mea por o he planed exer cse f on an MDI egmen A snack w compe cabohydates s oen eued aer polonged execise o epleish gycoge stores sce glucose iato ca be pooged i msces and e iver In overweghtobese atens decasng he suin ose insead of gesing snacks bee exercise can avoid addional weght gai oo im g o sppig o meals o cosmpio o smalle aouns o' od whou an adusmen o sli doses o oal hypo gycec agens can case ypoglycemia. se o a no physiologic sldig scae isl egime or se of a aggessve suppemena isn corecon ctor egien s oen the etiology o ypogyceic events A edctio n kidy functio pariclarly ldey paes can decase cleaace o sin or sn secretagogues ad ead to prooged hypogl ycea. Acoho consmpio can cause dayed hypogl ycemia eatme of hypogyceia is wod: mmediae co econ o ypoglycemia and prevetion of fe events a paet s conscios o 0 g o a cabohydae wt glucose shoud be consmed Gucose ables or gcose gel ae deal eamen egmens The blood glucose eve sould be checked agan ae 5 mntes and cosumpio o o 0 g o gcose sold occur aga f e hypoglyceia does o prove to greae han 70 mgd 39 mo/). Since the efcs o e insu o oal hypoglycemic agets ae iey sll presn a eal o sac shoud be consumed afe he m vey patien w diabees o medicaios associaed wih hypogycema sold eceive a pescrptio a glucagon which shold be sed wen oal cosumptio o guose is o ossbe o sa. Reaxig e gycemic agets ad hemogobn A goals ad edcig doses o therapeuic agens wil decrease the isk of fte ypoglycemia A review o a patiets dabees s anagee sklls can also hep detiy recuring is ctos r h ypoglycema C
Di sor des of Gluco se Metabolism
KEY POINTS
Fsting Hypogycmi
• 7 /L 3 9 L • R A k
useced hpoglmi 1 h s ithr sonnous or egins ar a [s hould e \uaed b th llo\ ing simuaneous laboory measumns gus isulin. pepti in sulin. hdrxuyra and insuin secretagogu scn epde n oinsuin m ures of th noenous pducin 0 insulin I lyu rae is suprss ndoenus , ognous insulin ut \ld b unsu prssed n nom1 physiologc s of hpogmia or in a non insulin mdated ondion I' hoglycmi is no re sn a h i o \u, ion hou !1s is ind,ted. hich is ic,ll pr<m in consul1io \th an noci nologis. his s nv ol\ s msuemnt o he abo\e mntone lborator lu er 6 hous unl th lsa ucse Je·l hs g mmo ) an sus qunly r y 2 hours unil si'i plas g lucose stom o m eria r his st so inlves msurng th rspons o g luc 1go 1inisrion Euion > ni insulin ioicn ct th cn iion o nsulin utoimmun hpoglycmi, as he undly ing tiology r h hyogymia
C Hypoglycemia in Patients Without CONT
Diabetes Mellitus
Hyolema in patiens hout iaes is rar. hus e\alu aon ahologc hyolyia shoul only ccu hen Whe riad s sent: ymtomati hypogl yma docu ne hoyema a 55 g d (. U lo n ot smtoaic reie ith orrecion o hpolcemia ogyceia shoud no b conmed Yih POC gluc" monitos bu instead ith a or accur slhd labor1 or mehod. Hyogyceia in piens wihou diabs s usualy lae to dugs ilness homonal cin. 0 il cl tumo endogenous hypeinsulinism noninsuinoa anceaoenous hogl yemia dpion of ht c glygn or o alcoho insion Diagnosic suds shoud b obaind during a ontanous hpogycmic epsoe or du ing an attemt o recreat a scenaro nown to C,lSL' hypogl cma uch as oloned [�sin or a 1 ixed m1 \Nhich cons o th t o >o that nus th hyoglyia yal a simle cabohda-h a such as oran juice ancas and syrup yolmia has cassiG1ll een catgorized as occurng in h sg vesus ostpnda ae athouh the etolos o eah o hes assi ,ons o hyocemia ar not muually clusiv The drenial diagnoses asd on he aboatoy s sults und in Table 10. Jaging stus shoud no ou unss bohia eden o endognous hyinsu Iinism s n red nd is eaed to a tumo or pancreaic abnorai
ABL 1 0.
Poprdi ypogym
osrandi hpoglycmia ihou a hsor o a rio bia ri rodur is r pcaly ours \hin S hus od consupion mid m olc es s usual r d in onsulton ih an noinologis nd asurs th glucos l\l s sympos ocur lus. nsuln. roin sulin. and pepid ls e measur pio to he meal and mnu int·ls or th im osymomai hpoglmi (boo gus l\l g mmo I) wihin h S hours aftr m ons umpton I' smtomaic hpoglyi1 ous. nsulin noies ar easurd d an ora hyoglci gen scning est is oined Tr1men \ih or wihou h d ion of hooi hyoyi on h mid mal s ofn nol\·s sll ruen cmlx
Di een ia Diagnos is o ponaneos Fas ing Hypogyceia• in a a ien W i ho Diae es
Diagnosis
er Insin
lasa C-epide
lnsulinoma
i
i
Suepios use of sulfonylreas of eglinides
i
Suepios use o nuli
i
Insu auone hypoglyceia
i
asa oinsin
er �hydroxyyrae
e Insin Aniodies
Urine o Bood eaolies o onylreas o egiinides
.
Negative
Negaive
Negatve
Posve
Negatve
Negaive
Posie
egatve
'Symptomac hypoglycemi, fstng plsm glucos 55 mg/d (3.1 mo/L) or lowe pompt symptotc elef wt coecto of ypoglycm Whpple t) Data om Cye PE, Axelrod L Gossan AB et al Evauation and maagemet of adl hypoglycemc dsodes: a Endocne Society Clca Pace idelne. J Cli El Metb 209 Ma:94)79-8 [PMID 19881
13
Disorders of Glucose Metabosm
m ,ls compoed oron. �. an cboh<1te o aoi he
Cl snsaion hypogcemi COiT.
Acute Complications of Diabetes Mellitus Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome Diabeic ktocisi ) and hypgcemic hyosmo IJ r synrm I I S re cue comIicains o nconoll hpgl cmia ih ihreann consunce i no rgniz and re ear picall occs in h eing o hyprglycemia ih rlaive or absolue nslin leficiency , < nease cou nteru laory homons uf'icin mons o inlin ar no peen to uppss lpol sis and oxi ion o fr ty acis which ess in keone b prdcon an sbequen mabolc acoi oc mo freuel ih tpe I iabe ahough o 30% o as occ in paient ih ype iabes IS occu n he ting opaial inlin ecnc hat i moe pical o pe 2 ibees he is suicien insulin in ient h H o spres ipolsis an rucion o' kon bodie. bu indua amon revn he hprglycmia dhdin. and hypemoaliy chac eisc o' HS S\·ral rik cors G ecipia th dvopmn o xreme hprgcmia: incion. intenina or inaveen insln hrpy nonahnc mocadial incion sress auma cnundin mdicion. suh as uccoi cod or cal anischoic agns In aton A may b he inil inicl presenaon in ome patens ith prvi osly unagnoe ype I o pe aee n iln o vn tha eads o ehdraion wil ofn recipit he hypc mia asociad ih I I Sympoms o' exreme hprglcmia n A an HS nclue po yu poldpia unnniona igh l vomit n. weakns an mnation changes hrtn and me boc abnrmaltis wn a hpeglycmia pres whch can ead to repiao fiure. leharg. obundaion. coma an eah KA can occu hin val hor o he inciin vn h dvlomn o HS i s acu han K and may ake dJ to wees o dep HHS ypical preent wh mre exreme hyperglcemia and mnal stas chanes mpaed h K h iii i f hpi ild eloic sdie (pasm gucoe. erm keons. boo ra niogen. reainn ecl y. cacuad anion gap. ari blod ae omaly. mpee bood cn wih dirnial oo cutue). un sdies etn. rinal yis. uin cr). che oraph. an an ecadogrm Urine n seum ones ae elevae in hoeve. a naiv masurment nil does no exclde K dobue is he mjor one bod in OK t 14
eone laboao measrmens en e th niprusid eactn whch on esima aacea an aceone lev es ha ma not be eleed iniia Athouh herycemia s th pcal fndn <1 prntation ih A paient can presen th a ran opasma lcose value ncdng ho in h normal ane F The anion ap is ee ae srlae m lekocyss i oen peent igh vels o leukocos may indae an nctios pocess as he eoog y o the hyperma Seum om evel can low t omoic shi of ater frm th naclla o eracelua space Nma o levae serum sodum ls a nicae ve vme depeon Srm poasm evs ma be eevaed due shts om the inracelluar ercela space d to eoacoss an h abnce o ufin inulin ma or o potasim lvels on prntation nicate o pasium sos in he bo wih need fr corection rir o intiat ion of nsuin herapy av aia arhhmias. Srum am e and lipae lels alo cn b eevatd n th abence o creait HS ypicall reens ih normal smal amuns oine o serm ketones Plasma lucose vae in HS ae icall reate han in OA an can eceed 20 m (666 mmo The erum smolali is evaed reate han 3 msm/k 2 Th rm iabonae vl s gar than 8 mEq/L mml/. an the pH rmans geae han 7 Tatmn OA and HS reque cecon hp rgcemi wih ntaveno nin insns. fqn mo n ong and eplacement o ectts orection hov olma wih inavenus fuds and psibe corrcion of' aciosis ) h C is the s pace f manaement o seee hpelcemia because o the qen monion reired ith ntravenous nsuln heap he ne r mnirn r potenia eecoteinduced arrhhmia and the poenal rpi mpenaon lama lcos lvls hould be montord initial vr hour whi on nsin inon hapy lcls shud be moni eve o 4 hos dpenin on inial eectle fcts and of' acioss C KEY POINTS
• d ; l c b • c
Disorders of Gluose Metaboism
28
Hypeosmola 26
Normal
Noketoti
Range 24
22
20
18
16
: E
14
12 I
10
8
Cassic 6
Euglycemi OKA
4
2
0 100
200
300
400
500
600
700
800
900
1000
5.6
11.1
167
222
278
33.3
38.9
444
500
55.5
Pasma gluos (mg/d [mmol/L)
FIURE 1. Spectrum of etabolic decompensation that occrs diaetic keoacidoss. DKA = diaeic etoacdosis
TABL
ngn H ypgycc C (KA n HHS)
d
ni (g)
P
cn Aidi
Assess o volume status, hen gve 0.9% saie at 1 Uh iniay in a paets, ad contie f paten s seveey hypovoemc Swtch o 045% norma saine a 250-500 m if corrected serm sodum leve becomes nomal or hgh When te plasma glucose level eaches 200 mg/d(1 mmo/L) n paens wth DKA o 300 mg/ d(67 mmo/) in HS swtch to 5% dexose wh 05% nomal sale a 50-250 m
Give egular nsl, 0 /kg, as a travenous bos followed by 01 /g/h as an travenous nfson; if e pasma glucose level does ot decease by 10% he fst ho give a addtioal bols of 014 /kg ad esume prevos fsio ate when he pasma gucose level reaches 200 mg/d( mmol/) KA ad 300 mg/d (67 mmol/) i S edce to 002-005 /g/h, and maita he plasma gucose evel beween 50200 mg/d (8311 mmo/) t anon gap acdoss s resolved i DKA.
Assess for adequae dey ncon, with adeqate ue oup (appoxmaely 50 mh) If serm potassim s <33 mEq/L(33 mmo/), do o sa insul bu insead gve traveos poassm coide, 2030 mq/h hrough a ceral ine cathete tl the serum potassum leve s >33 mq/(33 mmo/) ten add 20-30 mq o poassium chloide to each iter of traveous fluids to keep e serum potassum evel e 00 mq/L(40-50 mmo/) rage he serm poassm m mm do ot give poassium code bt stead sa isuin ad iavenos ds ad ceck the serum potassim level evey 2 os
If p s <69, give sodim bcaboae, 100 mmol 00 m of waer, and poassim chlode 20 mq, infused over 2 ous f p s 69 o geate d o ot give sodm bicarboate
DK = diabetic ketoacidoss; HS= hyperglycemc yeosol yndome.
5
Disorder s of Gluco se Metabolism
Chronic Complications of Diabetes Melitus Cardiovascular Morbidt Cardiovascular disease (CVD) is a major contributor to mor bidity and mortalty among patients with dabetes melitus. Diabetes alone is an independent risk ctor r CVD and s considered a CVD equvalent Concomtant rsk ctors in patients with diabetes, such as hypertension, obesiy and dys lipidemia aso contribute to the development of CVD and should be dentiied early through screening (Table 12). The 8 1 oint National Committee (NC-8 recently revised its recommended bood pressure goals r patients with diabetes to 14 0/90 mm Hg or less, citing a lack of data to support ower targets. I n contrast the Amercan Diabetes Assocation (ADA recommends a blood pressure goa o less than 40/80 mm Hg. The ADA advocates r a lower systoc blood pressure (<30 mm Hg) in select patents (young ong ife expectancy increased rsk of stroke if this can be accom plished safely Alhough JNC8 does not specfy use of an ACE nhbitor or an angiotensin receptor blocker (ARB as initial therapy r patients with diabetes and hypertension in the absence of chronic kidney disease the ADA recommends preferential use of these agents in treating hypertension in these patents.
The most recent American College of Cardiology I American Heart Assocation guidelines base treatment recom mendations r patents with diabetes on age, the presence of atheroscerotic cardovascular disease (ASCVD) or estmated 10year ASCVD risk usng the Pooled Cohort Equations; a spe cific goal LDL choesterol leve s no longer used in these guide ines. Treat patents wth dabetes and known cardiovascular or other vascular disease with high-intensity statin therapy. In the absence of known cardiovascular or vascular disease pro vide high intensity statin therapy to patents with diabetes if the LDL choesterol level s greater than 190 mg/dL (49 mmo/L or the 10-year ASCVD risk is equal to or greater than 75%. Provde moderate-intensity statin therapy r patients wth diabetes and a 10-year ASCVD rsk less than .5% Consder withholdng statin therapy in patents with diabetes younger than 40 years without addtiona cardovas cular rsk ctors In contrast ADA guidelines contnue to recommend an LD cholesterol goal in patents with diabetes of less than 100 g/dL (2.6 mmol/L with the option of LDL cholesterol less than 0 mg/dL 1.8 mmol/L) in patients with clinical ASCVD. Therere, it is recommended that statin ther apy be added to lifestyle modications n patients wth dabe tes who have clinical ASCVD are older than 40 years of age with CVD risk ctors, or are younger than 40 years of age wth LDL cholestero not at goa
TABLE 12. Screenng Recommena ons honc omplcaons o aees ells Chronc Complcaon
Clncal Saon
When o Sa Screenng
Screenng Freqency
Preerre Screenng es
•
•
F
b
b
0 8z
e
"It is reasoale to screen eve 2 years i o diaetic retiopathy is preset ad to scree more ofe tha aally if diabetc retiopaty s advaced or progressig rapidly. Th Amia Diabts Assoiatio uidlis stat that it is asoal to assss prossio o disas a rspos to thrapti trvtos wit ot moitori o urie ami xcrtio. t is easoal to scre every 2 years i lipid paratrs are at goal.
16
Disorders of Glucose Metabolism
KEY POINTS
• High-intensity statin therapy is indicated r patients with diabetes and known cardiovascular or vascular disease; LDH choesterol geater than 190 mg/dL (4.9 mmol/L), or atheosclerotic cardiovascular disease 10-year risk of equal to or greaer than 7 .5%. • Moderate ntensi stain theapy is indicated r patients with abetes 40 years of age and older and an atheroscle rotic cardiovascular sease 10year isk less than 7.%.
Diabetic Retinopathy Among adults aged 20 to 74 years diabetic retinopathy is the eading preventable cause of blindness. Changes associaed with nonproliferative retinopathy include retina hickening om macular edema inrcts resuing in "coon wool spos or soft exudaes), hard exudates and hemorrhages. Wih pro iferative retinopahy neovascularizaion occurs secondary o chronic retinal ischemia. These new vesses may rupture causing intraocular hemorrhage and subsequent brosis and retinal detachment. Risk ctors r diabetic retinopathy include ong-erm diabetes, poorly controlled diabetes hyperension and nephropathy. Retinopathy can be accelerated in pregnant women with type 1 diabees. Rapid improvements in glycemic levels r pregnant women and nonpregnan patiens can tem porarily worsen preexisting retinopahy. Screening guidelines vary depending on the type of dia betes ime of diagnosis, and pregnancy staus see Table 12). Optimal blood glucose and blood pressure control can prevent or deay the progression of diabetic retinopathy. Laser photocoagulation is used to treat reinopathy as severiy pro gresses. ocal laser photocoaguaion of the reina can resore some vision and reduce the risk of further vision loss with macular edema. Panretinal laser photocoagulation reduces continued vision loss in proliferative diabetic reinopathy and severe nonproliferative diabetic reinopathy. Laser photocoag ulation can also reduce the risk of retinopathy progression associated with pregnancy. Intravitreal injections of antiangio genic agents, such as vascular endotheial growh ctor i nhib itors may also be included in the management of proliferative retinopathy and macuar edema KEY POINT
• Opimal blood glucose and bood pressure contro can prevent or delay the progression of diabetic retinopathy; however, laser photocoagulaton is used to treat diabeic retinopathy as the severity progresses.
dom spot urine collection or a 24hour urine collection. Persistenly elevaed levels of urine abumin excretion are dened as greater han or equal to 30 mg/g in a spot urine measurement or 30 to 299 mg/24 h and greaer than or equa to 300 mg/24 h. Urine albumin levels should be elevated on multiple sampes over 3 to 6 mont hs to diagnose albuminuria as lse-posiive elevations can occur in the setting of ilness, mensruation, recent exercise extreme hyperglycemia or hypertension, and hear ilure. Screening timelines r urine abumin excreion are und in Table 12. Annual measure ments of serum creatinine and an esimated glomerular lt ra ion rate GFR) can be utilized in conunction with the urine albumin measurement o determine the sage of chronic kidney disease. When the estimated R is less han 30 mL/min/ .73 m2, a referral to a nephrologist is recommended. Diabetic nephropathy can be prevented or delayed with opimal plasma glucose and blood pressure conto n non pregnant normotensive paiens with persistently elevated urine abumin excretion an AE inhibitor or angioensin receptor blocker ARB) is recommended to decrease progres sion of nephropahy. In nonpregnant hyperensive patients wih persistenty eevaed urine albumin excretion and hyper tension the ACE inhibior or ARB should be titrated to achieve a blood pressure goal ofless than 130/80 mm Hg. Measurement of urine abumin annually after initiation of therapy with an ACE inhibitor or ARB is reasonabe to assess disease progres sion and therapeuic response as evidenced by stabilization or reduction of urine albumin excretion. Data are conicting regarding the ability of low-protein diets to sow the progres sion of kidney disease but hese diets may be considered if nephropathy progresses while using an ACE inhibitor or ARB or after achieving target plasma glucose and blood pressure goas ACE inhibitor/ARB combination treatment is not rec ommended. KEY POINTS
• levaed urinary abumin excretion is dened as greater than or equal to 30 mg/g in a spot urine measurement annual measurements of seum creatinine and an esti mated glomeruar tation rate can be utilized in con junction with the urine albumin measuremen to deter mine the presence of diabetic nephropathy and, if present, the stage of chronic kidney disease. • In nonpregnant normotensive patients with persistenty increased urine abumin excretion, an ACE inhibitor or angioensin receptor bocker is recommended to decrease progression of diabetic nephropathy
Dabetic Nephropathy
Dabetic Neuropathy
Diabetic nephropathy not only increases he risk of progres sion to end-stage kidney disease, but is also a risk ctor r CVD. Measurement of increased protein excretion can be per rmed by two methods: albumin-creatinine ratio on a ran-
There are severa categories of diabetic neuropathy which may present separately or in combination Symptoms of diabetic neuropathy depend on the nerves) or neve root that is aeced and may present as cal or difse disease. Achieving optimal glycemic contro early in the course of diabetes can 17
Disorders of the Puitay Gland
prevent the developmen of neuropathy, and sustained optimal glucose levels can dela he progression of neuropathy. Distal smmetric poneuropath (DPN) is the most common rm of dabeic neuropath. It s characterized b a "socking-glove distrbution that ascends proximal DPN equentl presents as a sensaton o numbness tinging burning heaviness pain or sensitivi to lght touch The pain ma worsen at nigh and with waking Musce weakness ma occur in severe cases DPN s a risk ctor r muscle and joint dermiies such as Charcot ot and ot ulcers DPN evaluation ncludes assessment of anke reexes vibraion sensation with a 128-Hz tuning rk and touch with a 10g monoament and pinprick Screening intervals are und in Table 2 Management o DPN smptoms ma require one or more classes o drugs icluding antidepressans (amitrpt line venlaxine, duloxeine paroxetine anticonvusans (pregabain gabapenin valproate, or capsaicin cream Autonomic neuropath can aect a single organ or mul ple organs Smpoms ma ncude gasroparesis diarrhea constipation neurogenic badder abnormal hidrosis and erectile dsunction Cardiac smptoms include resting sinus tachcardia orthostatic or postprandia hpotenson exercise intoerance and slent mocardial inrcion Cardiovascular auonomic neuropath is an independent risk ctor r mor aity, which underscores he need o reduce other cardovas cular risk ctors in these patients Diabetc amotoph occurs n older paents or those with tpe 2 diabees and ma be due o inrcts n he maor nerve trunks of the eg It can present acute wh severe pain and asmmetric proxmal weakness or pain in the eg weight loss and autonomic neuopath Partial remsson ma occur over man months Wihout an approved treatmens r dia betic amotroph managemen conssts of smptomatic ther ap r neuropathic pain and ambulaor aids if necessay Mononeuropathies can occur acue wih a cranial or peripheral dstribution There are no specic reatmens r these mononeuropathies as he smptoms usual resolve wihin a ew months Neve compression sndromes such as capal unne sndrome or peronea pals occur equen in patients with diabetes See MKSAP 17 Neurolog r more inormation regardng diabetic neuropay Refeal to a neurolo gst r electrodiagnostc tesing or evaluaton r nondiabetic related eiologes should occur wih severe, rapidl progressive or atpica neuropahies
Diabetc Foot Ulcers Diabetc o ulcers ncrease the risk r amputation and subse quent morbidi and dsabliy The etioo is oen muliacto ra Loss of peripheral sensaton can result in signicant injues that m be undetected b the paient Peipheral arteral dsease predsposes to the developmen of ower extremi ischemic ulcers and impas healing. Atered leukoce nction fom hperglcemia can impede wound healing of nuries Clinicians should evaluate the eet a least annuall to assess r pedal puses sensaon ucers skin or nail infec18
tions pain anke refexes, and ot dermiies Patients should inspect their feet dail r earl detection of an abnor malit and wear appropriate otwear Athough patients with diabetes have dierent otwear needs the selecon of shoes should ake into account several mportant ctors: intended use plantar protection shape and on the ot, and stabilit ssues (see MKSAP Inectious Disease)
Hypoglycemc Unawaeness Frequent severe hpoglcemia can diminish the abiit to detec life-threatening hpogcemia. This unawareness is caused b ilure of the release of counterregulaor hormones to trigger an autonomc response o decreased gucose eves Continua avoidance o hpoglcemia r several weeks or longer ma help restore the bod's abili o detect hpoglce mia Plasma glucose leves should be kept greaer than 50 mg/ dL (83 mmolL during the time period when restoraon of hpoglcemc smptoms is the goal to avod unintended and unexpected hpoglcema Continuous glucose monitoring sstems can be useful r hpoglcemia management b alert ing the patient to rapid decreases in glucose leves to allow prompt correcion and avodance of hpoglcemia see Sel Monitoring of Blood Glucose KEY POINT
• Distal mmetric polneuropath DPN is the most com mon rm of diabetic neuropat and it presents as a sen sation of numbness or bg pan n a stockng-glove distribution; management ma reque one or more classes of rugs ncludng antidepressnts amtriptlne, venlaxne duloxetne paroxetne) anticonvulsants pregaba gabapentn, vaproate) or capsaicin crem
Disorders of the Pituitary Gland Hypothalamic and Pituitary Anatomy and Physioogy The anterior ptuitar is made up of glanduar tissue hat receives its blood suppl om he hpothalamus through the hpothalamic-pituia porta plexus whereas the posterior pituitar consists of direct extension of neurons om the hpothalamus Both he poral blood ssem and the hpo haamic neun anv m h hhalamu h puita b wa of the pitua stalk The hpothalamus reguates anerior puitar gand nction b snhesizing specfic simulating and nhibitng hormones which are released in he portal bood Posterior pituitar hormones are snhesized in the hpothalamus and travel hrough hpotha amic neurons to be secreted b the posterior pituitar gland he anerior and poserior lobes are oined b the Rathke pouch Table 13 liss he piuita homones and nia tesing r suspected pitu itar hormone excess or deficienc
Disorders of the Pituta y Gland
TABLE 13.
Ia Tesg o a Homoe ecec a Excess a Homoe Ecess
a Homoe
epea Homoe
a Tes(s)
ACT
Cotisol
24 hour rne ree coso (x2) OR ocurnal salvay cotisol (x OR oveight low dose deamehasoe est
AD
AH
Simutaeous sem, e sodum, and urne osmolaiy
G
IGF-1
IGF1
SH
hyoine rodothyroe
S, ee (or total hyroe
a Homoe ecec y ar Homoe
epea Homoe
a Tes(s
Comao Tes•
ACH
Coisol
Simuaeous ACT, coso
ACT stimlation tes
AH
A
Simuaeous serm sodim, rine ad serm osmolaly
Water depivatio est
L ad FSH b
Se hormones
Simuaeous FSH estosteone (male estol (female
S
hyroie, riodohyroe
Smutaeous S, free (o toal hyoe
ACTH = adrenocoicotopic hormone; AOH antidretic hormoe FSH " follicle -stmulating hormoe; GH growth ormone IG1 inslilike growt factor 1 LH lteinizig oone H yrodstilaing ormone. ee able 15 for additona informaton on confirmatory testig for pititay dysncton Rotie esting for defciecy is no ecommended witot specfic igs of deficiecy sc as amenorrea, gynecomastia or impotence
The anterior pituitary gland secetes and releases six hor mones: adrenocoticotopic hormone (ACTH) thyroidstimu atng hormone (TSH), the gonadotropins-uteinizing homone (LH) and icestimuating hormone (FSH) growth homone (GH) and polactin. ACTH is eeased in esponse to corticoophinreleasing hormone (CRH) and acs on the adrena gands to pomote the synthesis and secretion of cotisol. TSH s eeased in esponse to thyotopinreea s ing homone (TRH) and acts on the thyoid to stimuate thy roid homone poduction LH and SH are diferentially eeased om the pituitay gand in response to pulses o
gonadotropineeasing hormone (nRH). LH and FSH regu ae normal male and emae reproductive function. GH pro duction is reguated by somaostatin. Poactin controls actation and is inhibited by dopamine. The posterio piuitary gand secretes oxytocin which is necessary r parturition and antidiuretic hormone (ADH aso caled vasopessin) which regulates water balance. The pitutay gand is poserior and superior to the sphe nod sinus which povides surgica access to the gland and is adjacent to the optic chasm the carotid arteries, and he cav ernous sinuses (Figre 2)
A coronal MRI (ef) and sagittal M (right) showg t piuiay glad open ), piary sak (th ), opic chiasm (arrowhead, spho sins (sta) ad caot aty (cued ). FIGURE 2.
9
Disorders of the Pituitay Gland
The pituitay gland is best imaged using MRI with gadolinium Because the normal pituta is relatively small, a dedicated pituitary protocol that obtans hin MR sices through the sela is used
Pituitary Tumors Piuita adenomas which ae benign, are the most common tumor of the pituitary gland A umor less than cm is dened as a microadenoma and a tumor cm or larger s temed a macroadenoma Fg 3 Ptuiay adenomas are common. Auopsy studies document that 0% of the general populaton had undiagnosed ptuitary adenomas. requenty pituitay adenomas are ncidenal indings on imaging sudies completed r other easons Wen patients undergo brain MR 0% to 8% are und to have ncdental piita micoadenomas and 02% have incidental pituita macroadenomas. Cetain genetc muations ncease the chance of deveoping a piuitary tumor.
Approach to a Sela Mass When a sellar mass is noted, pituitary adenomas are most lkely; howeve, they need to be disingushed om other pituita esions and nonpathologic pituitay enlargement he pitutay gland s enlaged dfusely in untreated primay hypothyroidism and durng pegnancy When possible, maging of the ptuitay gland should be avoided o delayed in pegnancy and in untreated pimay hypothyrodism because gland enlargement on imaging may prompt an expensive and unnecessa evauation for pituita hormone abnormalty and umor
Pituitay tumors are almost always nonmalgnant Two exceptions are metasatic disease and the vey rare pituita carcinoma. Additonal kinds of noncanceous pituitay esons include cranophayngiomas, menngiomas and Rathke ceft cysts Inflammatoy and inltrative dsorders ncudng lym phocytic hypophysitis, sacoidosis hemochromatosis, amyloi doss Langerhans cell histiocytosis, lymphoma, and tuberculosis, can afect the pituitary gland. Lymphocytic hypophysitis is an inflammat pituitary lymphocytic intration that most commonly occurs in pegnant and postpartum women It may cause transient or per manent pituitay insufficiency. Lymphocytic hypophystis is treated wih gucocorticoids. A selar mass can compress normal suroundng tissue and impair norma neuologic and ptuita uncton Ptuta adenomas may also be functional and secrete excess homone N h J o n n d !) ) \ n ( e n h 1tn d · n d \ SH. ' e h o (G ) 11 ee n r11 d b � 6
3. A coronal MRI (lef) and sagital MRI (right showg a lage pituitary macroadeoma The ora ptuitary gland ad te otic casm cano be see because of copresso fom he t o Te tmor s nvasive to the lef t caverous sus Like, he tor apears heerogeeos becase o nera ecosis FIGURE
20
C
Disorders of the Pituary Gland
C a adoa w gw . CONT
MR s oud e d v 2 a e 3 e ad k a o w 1 d u cudd C
Empt Sella
Empy sela is diagnosed when the normal pituitary gland is not isuaized or is excessiey smal on RI i is a rdiologic finding and no a distinct clinica condiion The pituiary sea is said to be "empty because normal tissu is not sen The nding may be primarily due to inceased cerbrospial flui entering and enargig the sella or t may be secondary to a tumor previous pituitar sugery radiation, o nrct Empty sella can also occur as a congenital abnormality when the sela is orma size but the pituitar is sma Wen empty sela is und incidentally o maging a eauato shou be completed to determine if thre is a nown cause r second ary empy sea and if he paient has signs or sympoms of pituitary hormone deficiency A paien wihou signs o symptoms shoud be screened r cortiso deficiecy ad hypothyroidism with 8 AM cortiso, SH and ee (or total) 4. A patient with signs of pituitary hormoe deciency shoud receive a more complete biochemica valuato of the pituta axes based on the sigs and smptoms und Repeat imaging s not ecessay uless idicated as sur eillance r the underying patholo that resuted n the empty sea KEY POINTS
• ncidenaly noted pituitay tumors are common and biochemica esting is inrmed by ndings o n hisoy and physica examination • Initial tests r pituitay incidentaly noted masses incude masurement of 8 AM coriso, thyroidstimuat ing hormone ee (or total) thyroxine (T4 proactin, and insuinie growth cor . • Empy sella is diagnosed when the norma pituitary gand is no isualied or is excessiely smal o n R i is a dioogic inding and not a disi nc cinica condition
u a a v em d Vu d a v u v dag d u va u d o w o age v w v u ·u a aus o oss M. w ve a vde o g vo c aa ag vo du o a dao ag a u uo Pu u a a vad udg u dg u a euo m o Pu uo va vu u ug amag t v . d VJ a ug u cu a d u us s/ a C KEY PON
• ituitary masses can compress the normal pituitary gland causing hormone deciencies; a ar ge pituiary mass may cause panhypopituiarism in which there is impaired secretion of a pituitary hormones
Treatment of Clincaly Nonfunctioning Pituitay Tumos Noctonig ptuitay tumors that are gowing o causng mass efet ar teated with neurosurge The most common surgica approach is tassphenoida through the nares or the mouth A ver arge or nasie tumo may require craniotomy r decompression ndicatios r sugery icude mass eect particularly a isual fied dect; tumor that abuts he optc chiasm umor gowh or an inasie tumor (inading the bran or caernous sinus) Surgey should aso be considered i a patient with a tumor cose to the optic chiasm who pans to become pregant (due to the physioogic enlargement of the pituitary assocated with pregancy) Functiona pitutary tumors wil be dis cussd ater in this chapte, based o th hormoe in excss (see ituitary Hormone Excess. KEY PON
• onncionng piuitay tumors tha are growing or causing mass eec are raed wih neuosurge
Mass Eects of Pitutary Tumors
Hypopituitarism
Pua u u u : uo w a w Le ve o a Pua m om u m a cu u w d o o a ua o oes Baus op casm oad uo o u gad a age pua ma ug vo g Dedg o u ad sev v m . u
Hpopituitarism i caused by one or more pituitay hormone deciencie usuay resutg rom damage to the normal ptuitary gad a tumor Hypopitutarism can aso occur as a compication om sugery if the norma gland o the pituiay sa is damagd duing umo stion o diation therap Additional causes of hpopiuiarism are ised in Table 14.
Pu au oag o he u gd o g uta da c Puta pex a u u u d o ma d 21
C
Disorders of the Ptutary Gland
TABLE 14.
Causes of Hypopittarism
Pituary adenoma Pitay sgey Pitay radaton Pitay apoplexy Pittay iarction Caniophayngoma Meastatc mo Menngoma Lympocytc ypophysitis Sarcoidosis angerhans cell hstiocyoss ympoma Heochromatosis ongenita deficences Hypohaaic disease
CONT
expansion of the sea onens de o bleedng. It is an endo cne and nerosrga emer geny. Ae ACTH deieny is oon and can be ife-hreatening sspeted, stressdose guootiod replaeent shod be initiaed eergent y Patients wh vision hanges or oss assoated wih apoplex rie rgent sga deompesson. C Hypoptas a o de o postpa pary io (Seeha synoe) ease o eessve pospa eoage asg ypoeso ad hypopeso aets who ay ave Sheehan synoe sho be eer gety esed a eaed seoday oso eey A pae wth Seeha syroe wl o atae bease o poat deey; o eae s avaale o e ata ton Ohe omone eees an be evalaed 6 weeks afte devey GH ad goadotopn eees oe o eay we e pay gad s aag e y o aato sge o heoage bease e e es that syesze GH (soa oops) an LH ad FSH (goadoophs) ae os sestve o jy Seoday hypohyods (TSH eey) ad seoday oso eeny (ACTH deey) ofte or lae he sease proess ay adeoas a ase elevato poa de o sak opression eadg o a deease n opaeg bo o poa seeo KEY POINTS
• ay os a sgey ptay os ae e os oo ases o ypopas • Sessose gooo epaee so e ae eegey paes w ptay apopey o ao as we as eege esga eve o paes w vso oss assoae w apope eqe ge sga eopesso
22
Adrenocoicotopic Homone Defciency (Seconday Coisol Deficiency) Althogh seonday otiso defceny ay rest from dam ae to h pary and or putay sta that pais ACH podo it s ost oonly iaoge due o eogenous guooroid use that sppresses piary ACH sereon Paens wth seondary ortiso deeny have ony go orioid deieny he remainde o he adena gand fun tions noraly and the reninangioensn system s inat so these paens do not have ineraootioid deeny (see Dsorders o he Adrena Gands a dsusson o piay adrenal iue) Alhogh paients with seondary otisol deieny do ere sress-ose gootiois hey ae at ess ris hypotension hyponaema and adrena sis han hose with pary ortiso deieny (ilure o the adena glands) bease the prod on o'ineaoood s etained Aso unle patents wh priary oiso dei ieny paients with seonday oso deieny do not deveop hperpgenaton o boning o he sin beause ACH and its phorone esponsbe hese hanges p opioeanoon (OMC) are no hypeseee Ora ineabe inldng jon neons) and even op a guoorticoids are able o sppess ACTH sereion. Gootiods presibed a doses above physoogi eplae en r longer han 3 wees sold be tapeed when dison ned o alow eovery of he putaryadrenal ais: i ther apy has asted less tha 3 wees no aper is rered pitary-adrena ais reovey When apering gloorois the patent an be tran sioned to a hydoosone dose hat is J% o 20% ower than he evaen, en gooroid dose he dose an then be dereased by . 5 to g o hydootsone e vey 1 o wees When tapering with prednsone pe age oses y 5% to % weey ti the patien s o a dose o s mg daly and then taper by g eve o wees It is d t to tape deaehasone e to he liited g tablets avaabe he aper an be slowe sypos sh as igh headedness pesist Ate prolonged glooo use, reovey o he pititar adrena as shold be tested pror to dsonnng gloor tod epaement Spea y ong seru oiso shoud noralie o greaer han µg/dL 33 no when guootioids are withhed r 3 to 48 hos low ing he aper Even ae endogenos ACTH produon has erned paens ay require ore e o o an ade ae ACTH response to sess Afte dsontnuing he guo ortoid ape the patien an ndego an ACTH siaion es (Table o doen adeae glooioi response o sress The dagnoss ees on deonstting a ow basal seu orso eel hat does no inease appopriatey after smlatio wth he ACH anaoge osyntropn This s done by easurng eary moning 8 seum oiso se orsol eve ess han 3 µg/ (88 nol) is onssen wih orisol deiieny. A noa response is a pea seum orsol
Disoders of the Piuitay Gland
ABLE 15. �mg a Ia Tcq
Ipa
AC () f
AC ml
M rm rl l Am 250 µ AC. M l 0 60 m
m l >8 µ/(4968 m/) ml r
ADH f (DI)
Wr r fll mr ll
P m , l m. Mr lm mll r M rm m, mll r 2 r
Water depivaton test interpretation:
f r: Ur ml 600 mOm/k H 2 P 5% f Ur mll l fr 2 l rm ml Plm ml >295 mOm/ 2 rm m >145 mEq/(145 mml/) Dm ll f l r ml <600 mOm/ H 2 rm ml >295 mOm/ H 2 r rm m >45 mEq/L(45 mml/): G mr
r ml >600 mOm/k H 2 ml r r, ADH rrl f r r ml <600 mOm/k H , m mll >295 mOm/k H /r rm m >145 mq/L(145 mml/) r f DI Desmopressn challenge interpretaton
>100% r r ml f m l D 0% r r ml f ml r DI >0% r ml rl DI. <50% r r ml l r D
Mr ml 0 m fr 2 G rm (m)
Gl r
75 r r G 0, 0, 60, 90 120, 50 m.
G <02 /m(02 µ/) m . G 10 /m(.0 µ/L)( 0 /m [0 µ/L] l ) m
ACTH = adrenocoicotopic hormoe; DH = atidiureti horoe DI iabetes sipis GH = growth ormoe.
C geae than 0 gd ( no) hen the est esu is CONT.
noa patients no onge euie day cotiso epaceen but shoud ow "sic day ues ( inceasing coiso epace ent dose dung iness) up to a yea ae cessaion o daiy coso eaceen Sytos o seconday cotso deciency ncude weight oss nausea voting ighteadedness hypogyceia hypoension and yonat eia Seconday cotso decency s aso dagnosed usng an T suaton tes Seconday coso deciency can be teatening and us be eaed wit gucococoid epaceent oen wit hydocotisone aoug pednsone o dexaeasone ay aso be used. ydocosone (30 g d) soud be adinseed n o 3 ve doses o ydocoisone soud be dosed 0 o 0 g n the ong and to 0 g in the eay atenoon atens euie stess doses o gucocotcoids wen acuey l osazed o unegong e sess o' sug Fo odeae pysioogc sess (ino o odeate sugey w genea anesesa) hydocoisone soud used ( g d oay o navenousy in 3 divded doses 3 days) ednisone 00 g o deaethasone 3 g d n dvded doses) ay be used ateavey. o ajo
pysioogic sess (ajo sugey taua citica iness o cdbt) hydocosone (000 g d intavenousy n 3 divided doses; 0 0 gd the nex day tape to basene n 3 days) ay be used n ateatve woud be dexaehasone (8 g navenousy in 3 divded oses the atient as pituay apoey and genteegen neo sugey is anned wth no te Tstiuation test ing he paten shoud epicay be eaed with gucocoicois and hen eceve an T stuaton es to 8 wees ate sug ey C
Thyroid-Stimulating Hormone Deficiency Thyodstiuang hoone TS decency eads to sec onday o cent hypohyods Seconda hypothyds s cncay denca o piay hpohyoids see sodes o the Thyod and econa ypoyos s agose y eosng a siuaneousy nappopaey noa o ow TS and ow T 4 ee o oa) aients ae eaed wh eohyoxne epaceen n he sae anne as pa hypohyods howeve the seu TS canno be used o ono and assess adeuacy o hyod hoone epaceen dosng nsead
23
Disorders of the Ptutary Gland
the levothyroxine dose is adjsted based on ee T 4 levels wih the goal of obtaining a vale within the normal reference range.
KEY OINTS • Patients with seondary cortisol deieny have iso lated glcocorticoid deficiency withot mineralocorti oid deieny; in addition, they do not develop hype pigmentation or bronzing of the skin bease adrenocorticotropi homone and pro-opiomelanocortin are not hypersecreed • Seondary o central hypothyroidism is diagnosed by demonstrating a simtaneosly inappropiately normal or low thyroidsimlaing homone and low thyroxine (T) (ee or total) level.
Gonadotropin Deficency he piiay gland noraly secetes LH and FSH i response to GnRH fro the hypothalams and FS stilate the secetion of normal male and femae sex homones H and FSH deieny cases ypogonadotropi hypogonadism (see Reprodctive sodes Hypogonadotopic hypogonadism may be ased by GRH deiciency The mos common ase of GnRH dei iency in women s hypohalam amenorrhea which is assoiated wth excess exeise illness or anorexia Additional cases of GnR decieny incde congenital GnR deficieny and Kallmann syndrome a condition in which hypohalami neons esponsible eleasing GnR il to migate nto the hypothalams dring embryoni development Treatment of hypogonadotropi hypogonadism depends on he goas of theapy and whether the patient desies fertil it Fertility eatment reqires eplacemen of the gonadotro pis in e ad woen Premenopausal women who do not desire fertliy ay be reaed with estrogen and progester oneontainng oral onaeptives (aer assessmet of isk of thomboeboli disease Teament of pemenopasal hypo gonadotopc hypogonadsm is recommended to avoid loss of estogendependent boe at a yong age which od ead to osteopoosis Treatment of posenopasal hypogoadotropi hypogonadism is not indcated Men who do not desire fertility ay be treated with testosteone eplacemen therapy (see Reprodtive Disordes)
w Hm cc Gowth homone (G is vtal fo oa linea gowh ad deciency pio to pbety wil ead to shot state At pbey te epphyses close halting linea gowh In adlthood GH podtion is neessay nomal physioo b is not as imporant r gowh as dring hidood n adts GH defi ciency cases tge loss of mscle mass an increased raio of tty isse to lean isse and increased isk r oseopoosis G deiency s ofte he fis hormone defcency to oc whe a patient s deveoping pititary insien bt 24
solated adltonset G defiiency is extremey rare and its lincal signicane in adls is debated. Therere evalation r G deiency is ecommended in patients with at leas one known pitiary hormone decen Unornatel G ther apy has been sed inappropriaey as an altenative media tion GH natrally declines with age and does not reqie repacement The se of GH does no promote longevity and when sed inappropriaely can be hamfl Speccaly GH therapy can encoage cance growth wosenig the dsease in a patient wih ane o pomoing growth of an ot ndiagnosed caner Bease GH seretion is psatile tesng random levels is not diagnostically sel Theree GH defiiency is diag nosed by measrement of G1 A G defcieny s onmed by measring the response of serm GH on a stimatoy test sch as the inslin olerance test An insln tolerance test ca ries a hgh risk of sevee hypoglyema so referral o an endo crinoogist testing is appopriate A deision egading eplaemen therapy shold be made based on that patient's sypoms goas ad isks n onsltaton with the patients endoinologist Whe clin ally ndcated G defiency is eated wih daily sbtane os G inections n an othewse healthy adl treatment of G deiency can impove qaliy of life and increase the percenage of lean msce mass Also it an ede the is of osteopoross owever, the isks and benefts of therapy mst be carely considered. Replacement of G is cos prohibitive r some patients t is containdicated in paes with cancer and shold not be sed in patens with an neated pitiary mor de to potential simlaion of tmo g owth
KEY OIN • solated adltonset growh hormone deciency is extreely rae, and is linial signficane is debaed; evalation r growh hormone deiey shold be reserved r adlts with at least oe known pititary hormone defiien
Central Diabetes nspidus ea dabees isipids D es o adeate p dtio of adieti ooe by the posteo pti ay ad I the psee of AD aapo wae aes ae seed he oeg bles ad aow wae o be absobed e absee of AD eessve wae s eeed by e ideys Eeo of oe ha 3 les of e pe day "i e sevey of vaies w te opeeess o te deey atiets desibe id o eee poya ad o espodg st: paia is oo Fa ypeatea s sa bease paes deveop etee ths ad polydpsia ad wh ee aess o wae a aa se sod he gh oa ag e We paes do ot din eogh o epae te wate ost e e de to poo o abse this dive o a o ee aess to wae tey deveop hypeatea
VC
C
Disorders of the Putay Gland
C CONT
I he pe wh olyu s igos wih smlaneous lbooy evi o' iiiy o o i he ce o vd sum soium osmoll wh inppopey low i osmoly I ssy. w devo s om h goss s le ies wh mi l wih qu his div a ss o w my hoose o oms w hou ho moe eplm hey, bu highly symomi ou d oci h is wih esul sp iy io csse em I hose qug me, ho moe epleme s wih smoss Jsmio 8 giie vsopss, o !DV ih isy subcuneousy, o oly Desmoessi is o soe wl i h gasis so o doss muh high h insl o subuous oses Mos is wih DI equ ihe eveig dosg o i i s o w iy osg o esmoess I AD is ovp is wil evlo we ioo volume ovo, hyoemi C KEY POINTS
• n te patient i poyuria dabees insipidus s diagnosed by cnica syptos it sutaneous aborato evidence o nabiit to concentrate urine it eevated se sodiu and osoait and inappropriaey o urine osoat; a aer deprvation est can conr te diagnoss. • reatent of centra diabetes insipdus is once or tice day orone repaceen wi desopressin.
C Panhypopituitarsm Phypopiiism os whe pis lck l eo d poseio iury homoe oduio Pnhypoiuiism my be cuse y lg o essv puy umo o s complio o sgy lhe puiy sk is nsed d ig sugy o s he sl o m hyoiusm wll sul ly Pies wih phyoiuiism eqi log eeme o 1 oiso AD bs hs e ees be heg s homos e l epe o h pis eece oup wih scsso o he isks n es o hepy d io o eqg eogeos gooos oive eoduciveged wom wih hypoiis wll o go o sponos lbo nd wil o la hese egies e sse s hgh sk d os shoul b povi by mel speis es wih hypoiiism shoul w mi ieiio omeig hei phypoiiis spilly oig h ee sssose glcooo hpy smoi i i i
Pituitary Hormone Excess Pituar mos ae ced nctional wen ey secrete excessive amounts of orone Te os comon functiona ptuitar tuo is a polactinoa. GH and CTH overproducion by piuity os is important to recognize because te clinca consequences of oversecreion are poenially severe. TSHsecreting tumors cause ypertyoidis bu are extreey are Occasionaly a piuiy umo can ovesecrete ore tan one ooe os commony GH and proactin o ess comonly TSH and GH or prolacin
Hyperprolactinema and Proactinoma C Prolacinoas ae pituiay tumors a secee excessive amounts of polacin owever tey are not te only cause of yperproactinei (Tb 16). Te mos comon cause of ypeprolactineia s pysioogic; prolcin is eleased durng pregnancy and postpartum o cause ctao Npple siulaion suc s during sex can cause mld ypepolactnemia (serum prolactin <40 ng/ mL 40 µg/L]) Pysoogic sess coitus nd execise can also incese prolain levels up o 40 ng/L (40 µg/L) Nipple piercing can aise prolactin leves above 200 ng/L (200 µg/L. Clnicl beast examinion sould not raise prolacn levels above e efeence age uness evauation r mil production s pered bu if desired palpation of te beast can be defered until afer a seru proacin eve is measured. edications are a coon cause of yperproactineia (see able 16). npsycotic agents cause ypepolactineia due to ei andopanegic eec tat ineupts e inibiion of polactin by dopaine. Specic agents suc as risperidone o eocopraide ay aise e proactin evel above 200 ngL (200 µg/L Evaluio piuiay yperseceion wen a patien s aing a edication non to raise te po acin eve is dcu Wen te proactn eve is only idly eevated (<50 ng/L [50 g/L]) ay be reasonabe to assue a yperproactineia is a edication side eect. en signicanty elevated (>00 ng/L [100 µg/L]) eier te
TABLE 16. Ce Hpepcem gc
Mect
Oter
Pregnancy
Antipsychoc ages•
Prolactioma
Lactao
Metocopramde
Npple n
Cmetide
Puitary mor-salk compression
Verapam
KEY PONT
ethydopa
• atents t papopittas reue eong repace ent of troxne 4 corso and antiduretic oone because tese decencies can be eteatenng.
Opates
Hyhym Cioss Chronc ney dsease
Cocane "Includig rsperdoe. oazapn, haopedol hopomazne, ad opam
25
Disorders of the Pituary Gland
medication needs to be withheld to further assess or a pitui tary MRI obtained to evaluate r prolactinoma. Caution s warranted when discontinuation of an antipsychotc agent s being considered, and consultation with a psychatrist is rec ommended prior to discontnuation Another common cause of hypeproactinemia is primary hypothyroidism Hypothyroidism can cause diuse swellng of the pituitary gland that may resemble enlargement due to a pituitay adenoma on imaging. Therere, a patient with pri mary hypothyrodism and hyperprolactinemia should be treated with thyroid hormone replacement with retesting of the prolactin level once the TSH has normaized. Further evalu ation is ndicated if the hypeprolactinemia does not correct when hypothyroidism s treated. If pitutary imaging has noted pituitary enargement prio to treatment of hypothyroidism repeat MRI shoud be obtained when the TSH is normal. Nonfunctionng pituitay adenomas can also cause hyperprolactinemia by compressing the pituitay stalk and decreasing dopamne inhibition of prolactin secreton. It is important to distingush between prolactinomas and non unctioning pituitay adenomas as the cause of hyperpro actinemia because of difrent treatment approaches
Clinical Features and Diagnosis Physiologically, prolactin induces and regulates lactaton. Hence elevated eves o prolactn cause galactorhea Women are more likely to develop galactorrhea than men. Hyperpolactinemia also causes hypogonadotopic hypo gonadism because of negative feedback on GnRH LH and SH by high evels of prolactn Both men and women present with hypogonadism. Women of reproductive age often present ear ler than men because of amenorrhea. They may also have early menopausal symptoms. Symptoms in men are insdious and may go unrecognized r years. Both men and women with hyperprolactnemia are likely to be nferle and are at risk r osteoporosis. Postmenopausal women are already hypogonadal because o ovaian iure; therere hyperpolactinema may have minima clinical implications n this populaton Howeve, the cause of postmenopausal hypeprolactinemia stll requires diagnosis because it may be due to a piuitary umor. Diagnostc imaging s indicated in stuations in which there s unexpained hypeprolactinemia. The degree o hypepolactnema is useful in difeenti ating polactinomas om onunctioning macroadenomas. In general, large nonunctioning tumors cause mild serum pro lat elevati (<00 / [00 µ/]} m talk m sion. Macroprolactinomas raise serum prolactin leves to greater than 250 ng/mL 0 g/L). Ver y lage macroprolacti nomas may raise proactn levels greate than 0000 ng/mL (0000 g/). Therapy atients with microprolactnomas without symptoms of hypogonadism do not requre teatment. Symptomatic women wth microadenomas may be treated with either oral contra26
ceptive pls i fertility is not desired) or dopamine agonists Postmenopausal women with mcroadenomas do not require treatment Patents with hypogonadism from medication nduced hypeprolactinemia may be teated with hormone eplacement Unlike other pituitay tumors medcation rather than surgery is irstlne therapy r proactinomas Even patients with severe mass eect such as vision loss are treated with medical therapy initiall Rarely very large tumors or more invasive prolactinomas do not shrink with medica therapy and also rarel contnue to grow. In these patents surgey should be considered llowed by radiotherapy if growth recurs or continues After being debulked the prolactinoma may respond better to medical therap Prolactinomas ae treated with dopamine agonists (DA). The wo FDA-approved dopamine agonsts are bromocriptine and cabergolne Dopamine agonists typcally decrease the sie and hormone production of prolactinomas rapdl. Response to therapy can be monitored by checking seum prolactin levels 1 month after nitiating therapy and then evey 3 to 4 months. Decreasing serum prolactin usually correlates with deceasing size of the tumor MRI should be repeated in year r micoprolactinomas if the prolactin level normalizes on dopamine agonists. After umor shrinkage is conrmed, addi tional MR!s are not necessay unless the serum prolactin level ises An MRI should be repeated aer 3 months of medica therapy macoprolactinomas, or if pr olactin leves ae ris ing on therapy with good medication adherence MRI should be repeated every 6 to 2 months until the macroprolactinoma is stable on serial studies and the prolactin level is not rising. Bromocriptine is dosed to 3 times daily so adherence can be challengng When initiated t is associated with orthostasis and lghtheadedness and patients can have dizz ness nausea, and headache during treatment. Cabergoline is much better tolerated and moe eective at normalizing pro actin and tumor shrinkage so t is typicaly the initia therapy chosen. It is dosed once o twice a week but typicay costs more than bromocriptine Therapy may be tapeed aer the polactn level has been normal r 2 years, and there s no onger a visible tumor on pituitary MRI. After discontinuing the dopamine agonist pro lactn levels should be llowed once a month r 3 months, then evey 3 months r the rst yea and then annually thereafer a pituitary MRI should be repeated if the polactin level rises above normal.
Proactinomas and Pregnancy Hyperprolactinemia is a equent cause of infertility because of the eect on gonadotropin release. DA theapy lowers pro lactn, normalzng gonadotropin regulaton and alowing norma ovulation. DA therapy should be discontinued when the pregnancy is dagnosed. The pituitary increases in size during normal pregnancy, and proactinomas can increase in size as well The risk r signicant tumor epansion s negl gibe n patents with mcropolactinomas.
Disorders of the Pituary Gland
Women with macroprolactinomas are at risk r cinicaly signicant tumor growth or vision compromise during preg nancy. If the tumor is very large or abuts the optic chiasm patients should be counseled on risk of tumor growth during pregnancy, as well as the risks and benets of surgical resec tion of the tumor bere pregnanc D A therapy is sometimes continued during pregnancy if the patient has a histor of visual eld defect Pegnant women wth macopolactinomas should be assessed cincaly at east once pe trimeste and have visual fieds tested every trimester or more equently r vision change Changes in visual fields or severe headache are indica tions to proceed with pituitary MRI If the macroprolactinoma causes mass eect during pregnancy bromocriptine may be started I the bromocriptine does not decrease tumor size and reduce symptoms of mass efect surgical debulking may be necessar Nomal pregnancy causes hyperprolactinemia so hyper prolactinemia rom prolactinoma does not equre treatment during pregnanc Polactin eves should not be measured during pegnancy Postpartum prolactin levels return to normal within a few months and lactation becomes non prolactin medated KEY POINTS
• Poactinomas pregnancy and lactation or medications such as antipsychotc agents ae equent causes of peprolactiema • A patent with prmay hypothyroidism and hyper polactinema shoud be teated wth thyroid ho mone repacement with retesting of the prolactn level once the thyrod-stimulatng hormone lev el has normalied • opamine agonists (bromociptine and cabergoline) are rst-line therapy r symptomatc patients with hyper polactinemia and prolactinomas
Acromegaly Acromegaly is a rare dagnoss that s oen missed years because of the insdious onset and ae pesentation in pri mary care; however it has very serious implications r a patient's health and longevity and must be diagnosed and treated in as timely a manner as possible
Causes Acromegaly is the clinical syndrome that occurs when a pitui tary tumor secretes excessive amounts of GH in an adult patient Prior to puberty patients with a GH-secreting tumor develop excessve ongitudinal gowth and gigantism a term used to ndcate excessve growth and height above noma age Because epiphyseal growth plates require sex hormones to cose patients with large pituitay tumors causing hypog onadism will not have closure of their gowth plates and will continue growth into adulthood
Clncal Featues and Dagnosis n the Adut Patent wth Acomegay Patients have changes in cial structure such as a pominent brow and jawline an enarged skull a large nose cial edema excessive spacing between teeth and macroglossia The hands and feet may be disproportionately large Other manifestations may include arthritis skin tags diabetes mellitus hyperten sion colon polyps thickened skin and excessive perspiration Acromegay can cause severe obstuctve sleep apnea because of soft-tissue sweling and macoglossa Additionall t can resut in heart disease including lef t ventricular hyperroph cardiomyopathy vavular heart disease arrhythmia and dias tolic hea1 ilure Increased rates of cancer are observed in acromega including colon esophageal and gastric adeno carcinomas thyroid cancer and melanoma Acromegaly increases motalit likey due to cardiovascular disease diabe tes sleep apnea and cancer Ageappropriate testing r these conditions should occur r the lifetime of the patient with acomegay Acomegaly s diagnosed biochemicaly Because GH s pulsatile thoughout the da it is not useful r diagnosis so measurement of seum IGF- is used instead Excess GH is confirmed with an oral glucose tolerance test (see Table 5) because glucose normally suppresses GH levels to less than ng/mL ( µg/L) GH evels greater than ng/mL ( µg/L) are diagnostic of GH excess A pituitary MRI should be obtained once GH excess is conrmed biochemicall onsultation with an endocrinologist is recommended if IG- is elevated Treatment Treatment of acromegay is transsphenoidal tumor esection surgery is the only treatment that is potentially curative. In many instances cure with surgery is not possible and addi tional therapy is necessary to treat the residual GH excess and tumor Remission is achieved when IG evels are within the normal reference range r age and the response of GH to a glucose tolerance test is normal Patients not achieving remission require medication to decrease GH levels and the ong-tem eects of GH excess Th e nitial therapy of choce is injectable somatostatin analogues to inhibit GH seceton If a patient ils to benefit om somatostatin analogue teat ment high-dose dopamine agonist therapy is marginally efective when the tumo co-secretes prolactin If IG remains elevated pegisomant a GH receptor blocker is used. Pegvisomant efectively lowers IGF levels but patients on pegvisomant have risk of tumor growth because the medication works in the peripheral tissues as an antag onist to GH and does not decrease GH production by the tumor Stereotactic radosurgey (gamma knife) may be oeed to increase the chance of remission or cure xternal beam radiation carries a high risk of causing ptuitary insuffi ciency but the risk is decreased when stereotactic radiosur gery is used 27
Disorders of the Pituitary Gland
Wen el n ren nd rne et n ld be leted nnll Wen te ttr tr tble b e GF1 evel elevted d be reeted nnll nd tretent ld be ltered untl te GF1 dene KEY OINTS
• Are r wen ttr tr erete exeve nt rwt rne n n dlt ent reltn n ne n l trtre n enlred l, lre ne, l ede exeve n between teet rl, nd drrtnte lre nd nd eet. • Tretent ely rnpendl reetn; wever, n e tent djvnt rdtn ter r edl ter njetble tttn nle needed r redl dee
Gonadotropin-Producing Adenomas Gndtnrdun tir denma re tll amt nd re rated larl t nnntnn denm beue te eter d nt erete fnn nadtrn r d n erete en FSH r H t rde lnl ndre Oten e dan de tertvel be n ittl tnin f u ptl emen
Thyroid-Stimulatng HormoneSecretng umors TSHein tmr re extreme rre Tee tr eree TSH nd rltn r GH TSHeretn tr e rtrid Ptent wt TSHeretin ve eier n inrrtel nrl r TSH level w ltne elevn 4 nd T 3 level Te reent wt denl t ted wt n n TSHedted rtx (ee Drde f te Trd Glnd) After bem p f TSH exe btned ttr in remended nfrm ttr Nerrer rlne ter bt tent ten reqre ddtnl edl te w eter ttn n e dne nt
Excess Antdiuretc Hormone Secretion Te yndre nrre ADH eretn SlADH) e wter retentin nd ontre Cenrl nervu yte t tre erre tr, netn n e SADH bee te exeve releae tl nd tr ADH Al, rnent SADH a n lin f ttr er, rrn n t ne rd f tien rxe 3 t 1 d fer rer ee KSAP7 erl)
Cushng Dsease Cl Cushig as is Lh m us o ica css coiso puio u o a ACscig piuay aoma 28
Cushig syom s o ypcosoism om ay caus ogous o ogous A Cp o o h mos ommo caus o ogous Cug sym is Cushg isas Wh uiagos. Cuhig isas s associa h vasaig Jog m moi such as as mo i osiy hypsio iii. an osopoosis h ia sp vauaio Cshg sas is o s k iochmca vc o hypcoisoism (s isos o L h a as c Ap Cushg syom is om ochmicay. a puiay MRI shou oai o piu ay umo o a umo ss ha 6 mm is visuaz o MRI a 8 mg amhaso uppssio s is u o ia Cushig isas om an cop ou f C Ecopc ACH pouco m a nopuiay umo (mos o ug. pacas. o hymus cacomas is vy uncommo Damhaso is amis a . a oso s s a 8 A puary souc o' AC i spo o gaiv ack m hgh oss o amhaso. sup pssig coiso Jss ha 5 µg/ 8 mol h a opic souc o AC wi o hav suppss cis o J Jov s s has o ssiv (88) a sp cicy (STX,) Cushig isas. so aposa sius sampg I is o comm poaoy puiay su gy I a cah is ha hough h p a inus a CH vs i h s ius a compa ih hos i h pphy a h amiiso o coicoop asig homo CR) A cra o ppha gn gar h 20 CR o ga ha 0 ae CR s agosic o Cushig sas (9% ssivy. 9% eciy Imagg o h chs a adome is iica i pas ih a sus pc copc sou of A Treatment
Cush ig sa s is ea by assphnia puay umo scio hih may cuav doous AC puio i h main omal piuiay ga suppss a mova h umo u o ong saig hypcoisoism. so pas wih succssu sugca a m hav au ACH cicy a u guco cocoi pacm I ma ak up o yea o ogous AC pucon o u o orma a somim h hypohaamicuay aa is os o cov A sucssu seci . Cushg sa a cu. ad paes mus b moor auay o sva h ' hypcososm cu sugica ue s o ahved pais may od puia iao o mica apy Mic opios cud ihiio o aa eym syhei of coiso kocoa o or myape: e opami agos agoi o e somaosai aao pasioi Media u o Cushig dia has a aivy o sucss . u hypcososm ympom oo i acheva goa al pas h ogous Cushig yom
Disorders of the Adenal Glands
In ptin ho do n bene' rm srgcl ratmnt nd h hv n ndqut spns L medl r nt, ltl nltoy o v rg " ACTH n n opon. Hov th pin w q fon oo nd natio pln C CONT.
KEY POINTS
• C x p p (C)- py ; C y yp y x C-p C y p py y p py y yp-py- x
Disorders of the Adrenal Glands Adrenal Anatomy and Physioogy j p k p x y x p zn: z () z () z ( W z h yz y y P450 zy n pp n p z p y x p y y -- p Up n yp 1 p (MR ky p p y p z y P pp y p (C) f py C y y pk y y C p y p py p o Py ( xp p y p
Sy yp (DE) (DES py z y C y y ppy y Uk ypy z p p x- y p v y n yz o y (Figre 4). C p x p yp y p yp v y Npp ynz x- yp y p -p pp xy p n p y �p h p py opy p pph p p ypy
Tyosine
� J0 Dopamine ® � -
Norepephrne
®
Epephre
C
Normetaephres Metaepres C
anlymande ad _ ydroxymadelc acid � �-' FIGURE 4. Catecholamine hormones ae produed n he adea edla ad sympathe gagia. The pahways of syhess a degraaion ae shown Exeve ehomie eeion a ou wih heohomoyoas an aaanglonomas 1 = Tyrose hydoyase 2 DOPA eaboyase 3 = oame �·hydoyase 4 = henyehanoamn e Nmehytasfease (MT) 5 Monoamine oiase (MAO 6 = Caeomethyltansfease COM
29
Disorders of the Adrenal Gands
Adrenal Homone Excess Cushing Syndrome Cushing syndrome (CS) is a rare disorder aecting two to three persons per miion per year that results om eevated eves of cortiso. Poor suppressibiiy of cortisol with dexamethasone and loss of norma diurna varation n cortiso secretion are seen. Without treatment, it is associated with high morbidty and mortaity. However iatrogenic hypercortsoism fom the admin istration of exogenous ora inhaed, intra-artic ular or topi ca gucocorticoids is often seen n cinca practice and is the most common cause of CS overa. The pharmacokinetics and reative potencies of synthetic ora gucocorticoids are shown n Table 17. The sustaned administration of any syn thetc gucocorticoid above the norma physoogic cortiso requirement can resut in iatrogenc CS and hypothaamic pituitary-adrena (HPA) axis suppresson, but is more ikey to occur the onger the haffe of the drug. Doses equivaent to prednisone mg/d or ess are unikey to cause cinicaly sgnifcant HPA axis suppression, whie those in excess of to 20 mgd commonly do after 3 weeks or more of consecu tive use. Endogenous CS can resut om ACTHdependent and ACTH-independent causes Cushng disease, which resut s from the autonomous secretion of ACTH by a corticotroph adenoma of the ptuitary gand s the cause of CS in more than two thirds of patients (see Dsorders of the Pituitary Gand). ctopic ACTH secretion by carcnomas and carcinoid tumors (usualy bronchia orign) is ess common, accounting r 10% to 1% of cases whe ectopic corticotropin-reeasing hormone (CRH) production s rare. The most common ACTH ndependent etiooges of CS are adrena adenomas and carci nomas, whch coectivey account r approximatey 0% of CS cases. CS must be dierentated from other disorders and cin ca states that are assocated wth physioogic hypercotisoism (pseudo-Cushing syndrome) Causes of pseudo-Cushng syn drome include severe obesity, poycystic ovary syndrome, pregnancy, anorexia nevosa, depression alcohoism and extreme physica stress as in the setting of infection
Clinica manifestations of CS are isted in abe 8 Cinica ndings that are highy specic r CS incude centripeta obe sit cia pethora abnorma t deposition in the supracav icuar or dorsocervica ("buflo hump) areas, and wide (> cm) voaceous striae (Fige 5). It is important to initiate evauation r CS in patients who have specifc signs and symptoms of CS, rather than n patients who are dfusey obese, have nonpathoogic striae, and are havng trouble osing weight because endogenous CS is such a rare condition with a costy evauation agorthm. Biochemca testing s used to estabish the diagnosis of CS It is crtca that the biochemica diagnosis is rmy estabished prior to any imaging studies due to the reativey hgh prevaence of cnicay insignicant pituitary and adrena nodues At east two rst-ine tests shoud be diagnosticay abnorma bere the diagnosis is conrmed. Initia tests incude the overnight low dose dexamethasone suppression test (LOST), 24-hour une ee cortisol (UFC), and ate-night (N) saivary cortiso. A three tests have smiar diagnostic utii but the OST or N saivary cotiso tests are more convenient. The 4-hour C and LN saivary cortiso tests shoud be permed at east wce to ensure reproduciblity of resuts Because the secretion of cort so is pusate, measurement of random serum cortisol s neither sensitive nor specic r the diagnosis of CS An agorithm to estabish the diagnosis of CS is shown in Fge 6 Referral to an endocrinoogist is indicated f two inita tests are abnoma
I U RE 5. Wide violaceous striae are seen o the abdomen o f a pie wi Cusg syrome. Srae arge an 1 in wd are ihly specifc for ypeorisoli
TBL 17 Dse quya!'�d j v� _ eces < Cmm S�c Oa ucccds ec uccrcd qae Bgc eae epaceme Hae ammar e (m)• ( Pe h
eae Meaccd Pe
0
8
Prensoloe/prenoe
8
4
Methylpredisooe
4
8
0
Dexamesoe
07
0
0
Hydocortisone
Denoes oo gluocoioid dosng for prary adrenal falue eqvalet to ydoosoe, 20 g bAnti-flamaor poency relative to hydocoisone. 'Mneralocortiod potny tv to fudooiso.
30
Disordes of the A denal Gands
TBLE 18.
Cc Feue Cug Sydme
Spe dg
e Spe dg
Ased d•
Cetipetal obesy Facal plehora Supacvc r a pads Dosocervcal a pads We sre voaceous
Easy brusng xcessve ragly sk Proxma musce wekness Impare emoy Tempoal bag Hrstsm ( woen) Mesrua abnotes
Oseopoross Hypeeso Dabees mells Obesy Depesso Hypoea Nephrohss V/
b
b
b
PE= pulmony emboism; VE= veos tromoemolsm. aMedic dsorders tht my e see i ssoctio wt bt re ot specc fo Cushig sydrome Fetres of droge excess see wth ptty corcotrop deom or dreocortcl crciom
In he standard LOST, dexamehasone (0.5 mg) is admin isered every 6 hours r 48 hours and seum corisol is meas ured a 9 n he overnigh LDST 1 m g of dexamehasone is adminisered a 11 PM or midnigh a nd seum corisol is meas ued he nex morning a 8 Wih eiher es, serum corisol will ypically be suppressed o less han 2 µg/dL (55 nmol/L). Sandard assays measure oa serum corisol or ha which is bound o corisolbinding globulin (CBG) and
A.
A.
f t
oher proeins. Therere he LDST should no be perrmed when CBG is likely o be abnormal such as wih malnurion cirrhosis he nephroic syndrome and hyperesrogenemia (oral conracepive pills or pregnancy). There is no clear asso ciaon beween dexamehasone responses and BM! or weigh and herere he LDST may be used simiarly in he obese populaon. The LDST is bes avoided in paiens aking medi caions ha coud accelerae dexamehasone meabolism such as aniepilepic drugs (phenyoin phenobarbial and carbamazepine) rimpin or piogliazone. Concomian measuremen of serum dexamehasone can conrm alered dexamehasone meabolism and paien adherence. Measuring 24-hour UFC crcumvens probems relaed o coisol pulsailiy and binding proein abnormali ies. he es should be perrmed a leas wice o ensure accuracy To con rm adequae collecon 24hour urine creanine is also measured (normal range 225 mg/kg/24 h [177221 mmol/ kg/4 h] in men; 152 mg/kg/4 h 1331 mmol/L/24 h] in women). A es is considered abnormal when UF C exceeds he upper imi of he normal range of he assay (45 g/24 h 4 nmol/24 ) while values greaer han 3 imes normal are diagnosic of CS. Less marked elevaions are seen wih pseudo Cushing syndrome and polyuria. A lsely low FC can occur in chronic kidney disease and when CS is subclinical or mid. The LN salivary corisol es is perrmed beween and mdnigh The nomal evening nadir in corisol secreion is los in paiens wih CS, while i s preserved in paiens wih pseudoCushing syndrome. Boh emoonal and physical sress (r example exercise) can cause a physiologic increase of salivary coisol. Faseposiive resuls are seen wih
f 24 : U' -1 L •
n u
rt
l
: n R n f ; na = l l FIGURE 6.
AMust be peformed a le twice.
31
Disorders of the Adrenal Glands
cigarette smoking o use of chewing tobacco. LN salivar cor tisol testing should not be perrmed n patents with erratic seep schedules (r example, shiwokers) After CS has been conrmed biochemicaly u rther testing is required to distingush ACTH-dependent or independent causes, and consultation with an endocrinologist is recom mended The st step is to measure pasma ACTH on two separate occasions With adrenal (ACTHindependent) CS, plasma ACH is usual less than pg/m (11 pmo/L), wheeas values greaer than 20 pg/mL (44 pmol!L) ae tpi call seen with ACTHdependent causes Plasma ACH values of to 20 pg/mL (11 pmol/L) are nondiagnostic but are moe likel to b e seen with ACTHdependent disorders For a discussion of the evaluation and management of ACTH dependent CS see Disorders of the Pituitar Gland The next step in the evauation of ACTHindependent CS s with imaging of the adrenal gands such as dedicated adrena imaging wth thinsection C or MRI Both studies have equal sensitivit; however, MRI is moe cosly Adenal adenomas and carcinomas can usuall be disinguished om one anoher rdiogrphicall (Tb 19). Suger is consideed frstine teatment adrenal adenomas and nonmetastatic adrenocor tical carcinomas (ACCs) When suge is deaed patients with ovet CS adrena enme inhibtors (metrapone keto conazole and etomidate) can be used to reduce cortsol levels and decrease the rsk of compications such as opporunistic nections and cardiovascular events he management of ACC is discussed elsewhee (see Adenocortical Carcinoma) ollowing adrenalectomy paients with adrenal CS will oen develop acue adenal insucienc because of axs
suppression and contrateal adrenal atroph om ongstand ing elevated coisol evels Al patients should therere be tre ated with stressdose glucocortcoids during the peioperative peiod and continued on phsiologic replacement until HPA ais recov e has been conmed Following successl surger the phs cal changes associated with CS can tae up to 1 ear to resolve. KEY POINS
• Cushing sndrome results fom endogenous hpecori soism o exogenous exposure o glucocoticoids; it is associaed with poor suppressibilit of endogenous cor tisol production with ora dexamethasone • The most common cause of Cushing sndrome is the administation of exogenous glucocorticoid therp r another medical condition • Iniia tests r Cushing sndrome include the overnight lowdose dexamethasone suppression tes 2hou urine ee corisol and latenight salivar cortisol
Pheochromocyomas and Paagangliomas Pargangliomas are tumors composed of choman cels Approximate 80% are intraadrenal (pheochromoctomas) the rest orignate om extraadenal smpathetic or parasm pathetic paraganglia he most common location r extra adrena smpathetic paragangiomas is the abdomen, whereas parasmpathetic paagangliomas are usuall und in the head and neck heochromocomas and extraadrena smpathetic paragangliomas almost alwas secrete catecholamines (norepi nephine epinephrine dopamine) however head and neck parasmpatheic paagangliomas almos never do
ABL ypc mgg Cctscs A Msss A Mss
v
C
MRI g tst•
Adrenal adenoma
Diamete <4 cm
Density <10 HU
soinense on T2-wegted mages
Homogeneous enhancement b
Contrast washou >50% (0 mn)
Rond, cea margins Adrenocoica carcinoma
sualy> cm
Density>10 H
eteogeneos enhancemen
Hyperintense on 2weghted images
Contrast washout <50% 10 min)
Irregla magns Calcifcatons necross Peocromocyoma
Variable size
Densiy>0 b
Heterogeneous enhancement aa
yerntense o weighted mages
Conast wasot <0% 10 mn
Rond, clea magins Can be blateral Metastases
Vaiable margins
Densty>10 H
Can be blatea
Contrast washout <50% 0 min)
HU = onsfeld ut (mee rdiodensity compred wit wte). aSig itety comred wth iver >Eeme oow itveo otr dition
32
Hyperintense on 2-wegted images
Disorders of the Adenal Gands
Although catecholamine-secreting tumors are rare over all, they are und in 0.5% of patients with hypertension and pheochromocyomas account r 5% of adrenal incidentalo mas (see Incidentally Noted Adrenal Masses). Most pheochro mocyomas secrete norepinephrine resulting in episodic or sustained hypertension. Orthostatic hypotension can also be seen and likely reflects low plasma voume. In addion to the classic triad of diaphoresis, headache and tachycardia com mon symptoms include papitatios tremor, pallor, and anxi et. Less common features are papiledema diabetes mellitus and cardiomyopath. Approximately 10% of pheochromocyto mas and 20% o 50% of paragangliomas are maignan. One third of pheochromocytomas and paraganglomas occur in the context of a genetic disorder. Pheochromocyomas are seen with multiple endocrine neoplasia (MEN) syndromes type 2A and 2B (Table ), neurofbromatosis type 1 and von Hippel-indau syndrome (VH). Paragangiomas and less equentl, pheochromocytomas can occur wth milal para ganglioma syndrome mutations some of which are associated with high raes of malignanc The diagnosis of pheochromocytoma and paraganglioma is based on conrmation of the excessve secretion of catecho lamines or their metabolites as measured in the plasma or urine Evaluation is recommended if clnicaly suspected in the evaluation of an incidentally noted adrena mass or in the setting of heredtary pheochromocytoma or paragangloma syndromes. The sensitvity of plasma ree metanephrines is the highes of any screening es (96%-100%); however its specicity s relatively low (85%89%) Therere plasma ree meanephrines wil reliably exclude a pheochromocytoma when negative bu further esting s needed to conrm the diagnosis unless the result is markedly abnorma (above 4 times the upper imit of normal). The sensitvity and specic ity of 24hour urine ractionated metanephrines and catecho lamines are 91% to 98% Due to the lower frequency of lse-positive results 24-hour urine measurements are recom mended when the pretest pobability of disease is relatively TABLE 20. ype
low (adrenal mass without typical radiographic appearance) while measurement of plasma ee metanephrines is preferred when clinical suspicon is higher (known hereditary syn dome) Referral to an endocrinologist is recommended when biochemical testing is abnormal. Many medications and other substances cause sely hgh leves of plasma and urine catecholamines or meane phrines (Tabe 21); therere discontnuation of these agents bere esting is recommended. If a catecholaminesecreting tumor is strongy suspected in a critically ill hospitaized patient CT or MR of the abdomen is the preferred initial test because biochemica testing cannot be interpreted reiably in this setting. ollowing the biochemica diagnoss of pheochromocy toma or catecholamine-secreting paraganglioma, radiographic localization is needed. Because most catecholamine-secreting tumors are located in the abdomen CT or MR of the abdomen and pelvis is the best inial stud. f negatve iodine 123 (123 )-metaiodobenzylguanidine (MBG) scanning can be per rmed Adjunctive diagnostic tests are CT or MRI of the chest or head and neck region. When multiple tumors or malignan pheochromocyto mas or paragangliomas are suspected MBG scanning should be perrmed preopeative. However r identifcation of meastatc disease fluorine 18 (18 F)-uorodeoxyglucose (FG) PET scanning is superior to other diagnostic tests Preoperative pharmacoogic treatment is mandatory r pheochromocyomas and paragangliomas to prevent life threatening cardiovascuar complications related to the mas sive release of catechoamines during surger. Preoperative blockade of -adrenoceptors, usually wth phenoxyben zamine is rst-ine medical therapy. The dosage is titrated to achieve a bood pressure below 130/80 mm Hg seated and greater than 90 mm Hg (systolic) standing. Commonly used bu non-FDA approved alternatives include calcium channel blockers and selective 1 -bockers (terazosin or doxazosin) �-Adrenoceptor blockers (metoprolol or propranolol) are
Multiple Endocr ine Neoplasm Syndomes
Mtatio
Most Commo Featre
Associated Feates
MEN1 (inheritance of one muated alele wit somatc maion in ote aee eads to neoplasia)
Paratyod adenoma (ofen mliple)
Panceatic set cel ad enerc tmors (gasrinoma, insoma most common Piita adeoma Oher (carcod mors, adreococa adeoma
2A
RET
(exo 11, codon 634 °
B
RT
(exon 16, codo 918
Medllary thyod cacoma
Peochomocytoma (oen mliocal)
Meda hyrod cacnoma
Pheochomocyoma (oen mlioca)
Paahyrod hypeplasa Mcosa eoma Gasroinesta ganglioneroma Maaod body aits
Most common muaion obsered.
33
Disorders of he Adrenal Gands
TABLE 21 . Subsaces ssca wt Fas-Psv Bcmca stg Pecmcytma rug Cass
Meca/ubsace
z
z
T
W
D (
Primary Hypealdosteronism
Py hyeses PA) esus r he s see ' eessve see P s evey oey 0% es h hyees dd sgs P lude hyoe eb lss. h ee eess vs y ly e see seg e ems (APA ses se pely 0% PA whees ey e cses e e o be are h yes U e hyes dosere-se eg e s (ACCs) e re h yper ses s s n es PA s e osdeed n a es h d' hyees shd aso e eed ens h hyees d ney e ade ss snes e-ed hyea. e sers c PA ccay hwever he ss hec es wl e ampes ncde sey hyeoseons (ren rery seoss e see s s seses (Le synre) CS er s gea de hyeasa CA) d i e-ced hyernelr ds seen PA s th he smes ese e drng bulry sma e aivy PA) s adsee cono (PA C n vole ee e e. esg s sve PC s >5 ]. PR s ee h My es d n hyeesve ges mes ens PC RA r bth ( ). oee es es degg seeng ofen have dgess ye eso dsoug otentaly dg ets e ns e Soppin nerlocood ee agnss (se eeee) 6 ees tes s eeded es shd so be se esg sse eem Ms he eons
E I
Most likely o cause flse-positve resls.
added ater to trea reex tacycarda but sould never be sarted bere adequate -blockade has been acieved due to te risk of ypertensive crisis om unopposed -receptor smuation A eart rate of 60 to 70/mn seated and 70 to 80/ min standng can be argeed in most patients ecause t s assocated wit fewer surgcal complicatons and shorer postopeatve osptal stays laparoscopic adrenal ectomy is preferred peocomocytoma except in te case of large o maignant tumors wen open adrenalectomy is requred Following the surgical remova of a catecoamne secreting tumor argevolume intravenous crystallod s administeed to couner hypotension. Vaspressors r exam pe, norepineprine are sometimes required Longterm llow-up is needed r peocromocytomas and paraganglio mas due to diculty dsnguising benig rom maignan tumors Metasases ave been eported up to 20 years afte dagnosis n addition o outine clnical surveillance annual measuremet of plasma or urine metaneprines is ndicated to assess r recurent or metastatic dsease Metastatic disease e e e 131 [- MBG terap cemotherapy and/or radherap Cre is not possble unless all disease can be sugically resected :i
KEY POINTS
• eocomocyomas are seen wit multiple endocrine neoplasia MN syndromes type 2A and 2B, neuo bromatosis ype and von Hippel-Lndau syndrome. (Continued)
34
• en clnca suspicion of peocmocytoma or para gangloma is lo, measurement of 24-our urine fac tionated metanepnes and caecolamines are te tests of coice because of teir jg specicity low lse-positive rates; wen clnica suspicion is g, measuring plasma ee meaneprines is preferred due to is greater senstivit
• eocomocyomas and paragangliomas require life long sureillance r recurrence wi annual plasma ee metaneprine measurement
O
(cont i nued )
• reoperative -adrenegic blockade is rst-line medical teapy r peocromocytomas and paagangliomas �-adrenoceptor blockers metopoll or popanolol are added aer -blockade to treat ree tachycardia
KEY OINTS
Dsorders of the Adrenal Gands : TABLE 22. e e Cmmy Pescibe Meia s Measuemes Plasma Re ivy a Plasmasee Ceai ', Ee es Mea lass PR P P/ Ress PR Fase-Psve a-Adrenoceptor i J gois
J
i
J
i
NSAID
J
i
ACE ihibior/ARB
ii
J
J
i
J
J
Diurec•
ii
i
Mnerococod eceptor gost
ii
i
i
J
P-Adrenocepto blocker Drec ei hibtor
alseNegave
Dhydopyrdne CCB
SSR
AB angioens reepor aaonst; CC B = alm hanel bloker PAC = plasma aldosterone oerao PRA = plasma ren acvy SSRI selee seoon reupake nhbor. o poassum-sparng (amlorde) and poassmwasn hyrolorohazde) des.
C cn be continued, bu reslts ust be teeed i cotex CONT
Fo empe if PRA is supessed despte ree wih ACE inhibtor o angiotesi receto bocker s likel y . If esuts e dic o itere epet esg aer emag otenti ierfeng medctos s advsed Verpaml hydrzne nd -blocers (doxzosin) ca be sbstted bood essre corl if ecessar Reera o edocrolo gist s recoended when sceeng tests e aboral Cofory testg is pered exce whe tal testig s dignostic r P as cases of spontaeous hypoa-
eia wh deecable R d C greer ha 30 g/dL 828 polL) Cotoy ess clude oa d irveos sat loadig d he udrocortisoe supresso d ctol chlege ess (Table 3) Oce he diagosis o has bee cored biochem cy dographic ocliio wth abdoil T s idi ced C is ecomeded ove MR i ost cses due to sir ecy d lower cos drel hyesa d eoas c ote be vslied d reocotcal caci om c be rled ou de vei slig AVS) s eeded os pates o deee the souce of ldoster oe secreo whe agg s reveg d to cor elzo whe iagig deosaes de ade oma VS s esec po olde ies ( 4 yes d oder) becase o higher freqecy of ouciong de cdelos VS should be ered epei eced ceters oy he goals o rete cude oveet blood pressue esotio o hyerteso is uely) orma ztio of seru possiu his is vey likely) d edc tio s ldostere ec se hyerdoseroeia s ssoced wh bood pressreidepedet icese in cdiovsclr evets The reaet o choice P ue o o uilaeral ade hyperlsi s Japroscoic reeco o pes with ilerl adrel hyperplsi or hose wih leal cuses of who ae no t surgca cadidates edcal her with erlocoticod gois is nd caed Sirooaoe is he os comonly sed edico due to ts rve ecacy ad costecveess leeoe s less liey to cuse sde ects gyecomast i e d esrul iegulres woe) becse o greater ne aocortcod recepo selec loide s ossiu sag duretic h bocks the aldoseroesesive sodm chel Use o'oide i s secodlie therpy becse of owe ecy
ABLE 23 abay Tesig Use e iagsis Hypealsesm es eas Cptop chenge est
Adminse: Cpopil2 55 g ory e the ptet hs bee seed o 1 hou esue AC, RA nd cosol d 1 o2 hous while seed
Fludocosone suppession est Orl s odig est
Adminser drocorsone. 5 mg oy evey6 hors for dys log wth sodum nd potssum sppementto
Psve I AC remns eleved d RA suppessed No esponse s sppesso of AC by %) AC>6 g/d (66 pmo/) RA < g/mUh ( µg/Uh)
Mese Serm corsol t7 nd 1 d AC nd RA o dy
Corso t 1 ower th )
Adminise Sodm chloide6 g orly dily in dvded doses)fo dys
2ho uie doseoe>2 g rie N>2 mq [22 mo/])
Mese2hou rine dosteoe nd rne o the hird dy tveous slt odig est
Adminiser: 2 L 9% sne itrvenosly over hours while supe
AC> ng/d (276. pmo/L)
Mese AC RA coriso nd serum Kt d hors
IM = ramslar V= nr aveos K = poassum Na = sodum PAC plasma aldoserone oerao PA = plasma renn avy
35
Disorders of the Adenal Gands
KEY POINTS
• Tesing r primary yperaldosteronism is w it te simultaneous measurement of midmorning ambulatory plasma renin activity and plasma aldosterone leves; testing is positve if pasma aldosterone concentration is anky elevated (>15 ng/d L [414 pmol/]), plasma renin activity is suppressed and a ato of te rmer over te ater is geater than 20. • Te treament of coice r primary yperaldosteronism due to an aldosteronoma or unilateral adrenal yperpla sia is laparoscopic adenaectomy; r patients wit bilateral adrenal yperplasia or tose wit unilateral causes of primary yperaldosteronism wo are not can didates suge, medical terapy wit a mneralocor ticoid antagonis suc as spironolactone is ndicated.
Androgen-Produing Adrena Tumors Pue andogen-secretng adrena neopasms are vey rare. Tese tumors usualy secrete DHEA and DAS and/or androstenedione wic are converted perperaly to testos terone. Approxmaey alf of androgen-poducing tumos are benign and alf are malgnant Manifestations of androgen poducing adrena tumos are usualy absent in adult men altoug decreased tesicua voume can occur In women apid onset of rsutism menstua ieguariies and vriiza tion can be seen and if present sould raise suspicon r tumoral yperandrogensm. Signs of virliation are deepen ing of te voice citoromegay and emporal air loss. Te diagnosis of an andogen-producng adrena mor is based on demonstating eevaed evels ofDHA a nd its sulte (usu aly geater tan 800 µg/d 21.6 µmol/) and/or androsten edone. Altoug adrenal androgen excess can b e seen in 30% o 40% of women wi poycystic ovay syndrome, mild eleva on ofDEAS (appoximaey 300 µg/dL 8. µmol) s ypi cal Adrenal imaging wi CT or MR s indcated llowing bocemical dagnoss of disease to ocate te umor. Treatment is sugica emoval of te tumor.
Adrenal Insuficiency Adrena insuciency may be due o lure of e adrenal glands (prmay adrena lure) or tere may be inadequae secretion of cortisol from te adrenas due to oter causes, including crical illness and ptuitay ACT deciency (sec ndr r dee Fr d ed coisol deicienc, see isorders o f te Pituiar Gland
Primary Adrenal Faure C Cc t Primary adrenal ilue is a rare disorder resutng fom a i ue in producon of al te ormones of te adrena cotex. Te overal prevaence is 10 to 15 per 00000 persons. Auommune adenalis is e most common eiology accounting r 70% o 80% of cases. Up o tw o rds of patiens 36
ave at least one oer autoimmune endocrine disorde and moe tan 80% ave adrena autoantibodies (21-ydroxylase antibodes) Infiltration of te adrena glands by tuberculosis (Addison dsease) was merly te most common etiolo of prmary adenal lure now it is responsibe r only 7% to 20% Replacement of te adenal glands can also occur wi metastatic cancer. Genetic causes include autoimmune poly glandula syndromes (APS) type 1 and 2, congenial adrenal yperplasia and X-linked adrenoeukodysrop. Adrenal cr sis resulting om biateral adrenal emorage can occu wit e antipospolipid syndrome disseminated inravascular coagulaion o systemc anicoagulaon. Te cinica pesentation of prmary adrena ilue depends on disease croncity and te presence of pysica sressors. In auommune adrenaltis e zona glomeulosa is usualy aeced rst wc is manifest by an increase in PRA. Wit nvovement of te ona sciculata a diminised corti sol esponse o ACT is seen llowed by an ncrease in basal plasma ACT, and lasly a decrease in serm corsol. Patients typically do not ave symptoms until ypocorsolemia o ccurs. b 24 sows te clnical and laboratoy manifesations of primary adrenal ilue ypepigmenation is a cinica all mark of s disorder tat is not seen wi seconday coisol deciency (seeDisorders of te Pituitary Gland r discussion of secondary corisol defciency) Adena csis may occu wen onset o f adrena ilure s abupt (batea adrenal emorrage) o wen inceased sress occurs n e seting of conic adrenal filure Manfestations of adrenal crisis include sock ypotenson fever nausea vomiting abdominal pain tacycardia and even deat. Aldosterone s critical to te maintenance of ina vascular voume and blood pressure wie coisol contb ues to augmentaon of blood pessue mosly during times of ncreased pysca stess (see Adrenal Anatomy and Pysolo). Aldosterone decency is te major impetus r te development of ypotenson and soc n patients wit untreated pmary adrenal ilure. Adenal crsis is are n te seting of secondary cortisol deficiency because e enin angiotensinaldosterone patway is inac.
D Te diagnosis of primary adrenal iure s based on demon strating nappropatey low sem corisol levels Because most assays measure total cotisol, abnomalities in corso binding proten or albumin can trigger spuious esuls. An rl mrn (8 AM) rum rl o e n 3 /dL (82.8 nmol/) is consistent wt cortisol decenc wereas vaues greater tan 1 to 18 µg/dL (414.0-496.8 nmol/L) ecude te dagnosis wen binding protein abnormalites and synetic gucocorticoid exposure ae excuded. o patens wit nondiagnostic basal corisol vaues (512 µg/dL 138-331.2 nmol/) stimulation testng wit syntetic ACTH (cosyntro pin) is indcated (seeDisorders of te Pititay Gand). A nor mal response is a peak serm coisol leve greate tan 20 µg/ d (2 nmol/L) ACT simulation testing sould no be used
Di sorders of the Adenal Glads :TABLE 24. Cia a aboao Maesaios o Pima ea Faiue Homone Deiciency Signs Symptoms oiso
Fatigue Weakness Low-gade fever
Laoatoy Finings
ypepigmeatiob (palmar ceases, exeso sraces, bccal mcosa) ecease i BP
Serm corso Plasma ACT
Aalgia Myalga Sal cavng Dizzness
Otostass ypoenson
RA 1 Sem sodm Sem potassm
Redced libdo•
eceased axiay o pubic ai•
Serm HEAS
Weght loss Aoexa
Serm sodium c 1 Plasma glcosed
Nasea/vomitig Abdoma pa
Aosteone DHEAS
ACTH adrenocoicotopic hormone; BP= blood pressure DEAS dehydroepiandosteroe slfate PRA plasa rei ativiy. "Women oly Qccrs exlsively i pary adreal faire oisol hiits te sereto of atidireti horone (AD), so ypocoisoleia will lead to reased sereio of AD ad ypoatemia ae in alts
r diagnosis in the critical care setting (see Adrenal Funcon During Critical llness). Once he dagnosis of cotisol deficienc has been esta shed, measurement of 8 M pasma ACTH wil deretate primar and seconda causes In pimar adrenal iure ACTH is tpicall greater than 200 pg/mL (44 pmol/L whereas it wil e ow or inappropriate noma i seconda corso deficiency Altough not speciic r the dagnoss hponatremia and hperkalemia ae chaacteistic o prmar adenal ilure and pincipall resut om aldoseone de cienc Treatment
Wiout appopae eatme pima adena ue s unm ta Even when teaed he moa o patients s wice tha o te genea popuaion Noma adea phso o cannot e epoduced exact e admistato o exogenous gucocoicoids and mneaococods oeove e admistto o doses o gucococod excess o psoogic epacemen can e assocaed wt deceased one mnea denst and eatures o w inceased s o metaoic sndome pe daees meitus peeso hpepdema oesit ad cadovascua dsease Avodace o conc oveepacemet s paamou Table 5 sows the medca eatmet o pma adena ue ost patents eque gucocotcod doses equvae to 1 to mg of hdrocosone da docotsone s admnsteed to 3 tnes dal we oce dai dosing o
oge-actg gucocotcods pedisoe o dexamehasone s acceptabe A paes w cotiso decenc need to eceve suctos o ceasn tei coiso repacemen dose dung ess "sc da ues' Patents shoud awas wea a medca ae decatio coas o paets w seconda coso decienc see sodes o te Ptua Gad those w pima adena ue aso eque mneaocoticod eplacemen Usua doses ae 00 o 0 mg pe da o udocotisoe easuemes o seum sodum ad potassium hep guide dosng Repacement o A s cotovesia t s o ind cated me but ca be consdered some wome wit pima adena iue oweve he ojective eeft s mn ima ad ee ae coces egadng the quat and sae o US pepaations whee A s cosdeed a suppement ate tha a pamaceutica Paies who pesen emegent w suspecte d adea css soud e teaed empca po o conmato o e dagoss A bood sampe soud e daw o serum cosol pasma AC ad ouine chemst es e patet sould eceve immedate eament wth 00 mg o dro cosoe navenous ad agressve ud esusciaon docoisoe s coued a 00 to 00 mg pe da in dvded oses (evry 6 ous ad te apeed o pso ogc epaceme cosol deicenc s cormed wth e aove esg Oe sthetc gucocotcods ca aso e used e teatme o adenal cisi s; howeve on hdo cotsoe supphsioogic doses has cnica eeva
37
Disorders of the Adena Gands
,TABLE 25. Cc Mdcl m Pm d Fu Bs s sders Med
'
Glcocorcod
Hydocorsoe
"Sick Day Rules": paient olows at home
Hydrocoisoe
Usaly 125-25 mg/d divided io 2-3 doses over te day
For mior pysiologic sress (upper respiratoy neco, eve mior srgey uder oca aesthesa)
Alternaves o hydocosone
2-3 tmes basal dose o 23 days
Prednisoe 25-5 mg oce daily
Se D: ealth care providers oow wile patien is i te ospital
exameasoe 02505 mg once daly
For modeate pysoogic sress mior o moderae surgey w general aestesa)
How o ose
Hydrocorsone 45-75 mg/d orally or IV i 3-4 dvded doses or 2-3 days
Trae to cliical respose w goal o o sigs o symptoms o corsol deciecy o excess icease dose i symptoms o coiso deicency emain decrease C sgns and symptoms ae peset)
Alteaves Prednsone 10-20 mg or dexamethasoe 2-3 mg/ 1-2 dvided doses
a
Pedsone Pednsoloe examethasoe
For major pysoogc stress maor surgey tama critcal ness or cildi) Hydocosoe 50200 mg/day V in 34 divided doses; 00 mg/day e nex day taper t o basee 3-5 days Aativ exameasoe 68 mg/d V in 23 divided doses
Miralocoicoid
0.0502 mg once daily in the morig
ldrocoisoe
How o os
ldrocoisoe s ot reqired if hydrocoisoe dose >50 mg/d
itae o Normal B 2 Normal serm Na K Adenal androe
25-50 mg oce daly
Consder A or women wth impaired mood or sese o well-beg when glucocoicod replacemen as ee optmzed
HEA BP blood pressure; CS= Cushing sydrome; DHEA dehydroepiadrosteroe IV i raveous Na soium K poassim. horter acg gcocorcoid may be preferre d over oger acig ages de o ower rk of gcococoid exce Loge-acig preparaos have e adaage of oce daily dosng (see Tble 17).
CJ
minealocoricoid ac tivity If ese. elecoye abomali ies ad hypogycemia soud be eaed ad pecipas of OH adreal css (r exae iecon) should be sogh and eaed s ciica ha aiens wi sspeced pray or sec ondary coso decency ad concoman hyohyroidsm be eaed wih gcocorcods rst because corecing hy d ooe deciecy wl acceeae he cleaace o coti sol and can precitae ace adea cisis e nomedcal liteaue he em ''adenal igue" has bee sed o desc be a constela ion of syoms. icdig difcly sleepng igue ad sat and sga caing yoteically om ong-e emoioa o ys i cal sess havin a deleerious eec on te aden glands, esling n a siutaneos ecess and de iciecy ofcoriso oweve ee s no scinc evdence o sppo is clam and te em adrea ige shoud no be sed Prooens of adenal ge pescbe synteic gcoco tcods ad suplemes conanig adena piui ay , or yohalamic etracs a ca case iaogeic CS as wel l s mineraocoicod speen ha can ead o h ypee sion aies sould eceie aopiae evaluaton r hei symoms and be edcated to avod akng ooal 38
reacemens wich here has no bee a deostraed bocemica nee d
Adrenal Function During Crtical Illness Gcocoicod dececy eaed o cica iess s an ety ta as o been wel caacezed has been posulaed ha cical less ay lead o sien p1ay or seconday cor tiso deciecy (AT deciency o an icrease tssue res is ace o corsol Te Aeican College oCca Care Medicie ecomeds cosideg tis dagosis i aies wi hyo ensio who have esponded insuceny o uds and vaso essor teray A maim icease in sem coisol of 9 g/dL 2484 ol or less owig he adminision o syeic ACT as been associated wit creas ed motalty o seic shoc: howeve ress o estng do pei beei om glcocoicoid herapy I he seig o ccal less bot CBG ad albmi coceions decease esling i lowe oa coso Fee corisol leves ee diecly measued o cclaed based on oal coisol ad CB may b moe rei abe i cicay ll aiens wih ypoalbuminea is o now fee coso evls povie usel ogosi inoa to Te ad1iistaio ofgcocoricoids as o been sow to bene ciicay l atens wo do no have soc ad he
Disorders of the Adenal Glands
esults of pacebo-conoled randomized trals n patiens ith septc shock are onctng. Futhe rsearch s needed o ca N hee s a popuation o crcay patiens who can objec tivey benet o gucocorcod heapy C
C
v
r
Adrenal Masses
C Adrena
Incidentaly Noted Adrenal Masses
masses are oen discovered ncdentay when abdomna agng s peed anothe ason These adrena incdentaomas ae seen on 4% o al CT scans and 7 of hose peored in paiens 0 yeas o age and ode he diferenia diagnosis nludes benign and maignant neoplasa of adrena corex or edula adrena cyss adena hypepa sia metasaic umos o nonadrena ogin, and nfecions and nfltaive dsordes he mos common cause of an adre na mass is an adena adenoma and adena easass is the neJ( os coon he two an goas n he evaluaton o an incidenally noted adena mass ae to ideni y adrenal masses ha are likey o be magnan and those ha ae assocaed wh hormonal hypeseceon so ha argeed traent can
Icidentally oted Adreal Mass
+ Imagig heotype
Imagig Pheoypeb
-
Favos Beig:
�
be undeaken popl An goh r he evalation and low up of an adena ass s shown in Figure . he sk o aignancy vaes according o sze Ony 2% o adrenal asses smaler than c ae cancerous; however 5'Y o those age han 6 c ae aignan An adrena mass·s sk o magnancy can be clariied based on is appea ance on C or MRI see abe 19 r the ypica radiogaphc atues o adena masses) Adrenal etastases accoun r about hal o adrena masses n patnts wh known nonadena malgnances Cancers tat metasasz o the adena gands incude ly phoas acinoas and elanomas Percuaneous biopsy s ndicaed o con the dagnoss of adrena etasasis: how ever ths should neve be pered prior to ruin g out pheo chroocytoa bochemcay Biopsy is no ecoended whn adenoorca cacnoma ACC) s suspeced because i canno elaby dstnguish bengn fo maignant adenocor tca neopasa h evauaton and anageen of ACC ae coveed in the Adrenocortca Carcnoa secion One quarter o ncidentaly noted adrena asses auono mousy secree hormones coriso %-0% caechoaines
Suspicious
• Size <4 cm
• Sie >4 cm
• Desity <1 O HU'
• Desity >10
• Cotast washout >50% (0 mi)'
• Cotas washout <50% 10 mi)'
I
Idcatios fo Adealecomy Suspicious imagig Gowth >1 cm/yea
omoal Evaluato
Fuctioig tumos
+ olow Up • Repea CT o MRI at 36 moths the auay fo 12 yeas • epea homoa evaluatio aually fo 4 yeas
Tests fo Homoe xces Cotsol
Adoseoe:
• Who All patets
• Who o K+
• Test: LST
• est PA/PAC
Catecholamies
• heochomocytoma • Aldosteoe-poducig adeal tumo • Subcca CS wh complicatios)9
Adoges
• Who: All paets
• Who: If suspected 1
• Test lasma o ue metaephes ue catecholamies
• Tes: DHAS, esosteoe adosteedioe
FIGURE 7. Algoithm or te ntial dagosc evaluatio ad ollow p of a cdetaly noted adena mass. CS = Cshig sydome; DHEAS = eydoepadroste one slae TN = ypetenso; U osied its K = potassim; LOS ow-dose (1-g) exametasone spesso test; PAC= plasma alosteoe coetra to RA plasa e actvty aReet imging d ormoe tstng re ndcd or drl msss no meetng crter for sugr t nl dgnoss. hr o Tb 19 or mor T nd MI ngs mgg s suscs n p know mgnnc , boy su o r o corm rn m r rg or pocromoyom omp. ca sn dngs
Posve srenng tess sll requre uer ocemc e ton o onrm dg oss {see text) Msre lsm meternes rdogr nc s tcl or ocooom; otse mesre 24·ou urne metnenes nd cteomes. Horonl eu ton or ndrognoducng drl tmor s ndctd ol clcll ssected sed on te resece o rsusm vrlzon or esrl rrgurtes n omn Adrenlecto s cosdred or conrmed cses o sclnc C S ssocted t recen oset o detes ertenson oest o lo on ss
39
Disorders of the Thyroid Gland
5%; aldoserone 1) Excess cotiso seceion is mos co
[: mon however he mjoriy o ptens have subcinical ds CrlNT.
ese wthou classic sigmta o CS . Despie hs, impoan compicons may e seen incuding oseopoosis hyperen sion diees melius nd cardovscular evens The LOST s the nial screenng tes of cho ce A seum coisol vaue greae hn 5 µg/dL (38 no) s consdeed posiive how ever soe dvocte using cu -o o8 g/d 4 97 nolL) to incease dignosc sensiiviy CS is sugesed y hisory or physica exminton Because he specifciy o he LOST is only approxiaely 90 the diagnosis o subclina CS shoud e confed wth ddiiona esting Fo a evew see the Cshing Syndome secton Aldoseonos are usuay smae hn 2 c Cse detecion PA s pered n al patients wth hyperenson or those on anhypeensve edctions Tesin uono mous secreion o adena ndogens is pered i clnically suspeced ollowing careu history and physcl exmnion Al patients wth an incidenl adren mass shoud be esed pheochroocyom Mesueen o 4hou ne meanephnes and cechoamnes s he peed st es in os sypoa pens de o he owe ncidence o se-posiive es resuls However i the adiogrpc pper ance o the drena mss is suspcios pheohromocy o (see be 9) or the pien is sympoc hen pls ee meanephrnes should be mesued see rary ypeadoseonsm Andogen-roducng AdenI u ors nd heochroocyos nd aragangloms) Adrenal asses ht e larger thn cm hose wih wo some dogaphic ndings nd pheochoocyoas should e emoved surgicly Surgey is so indced r unlate doseonos and is considered o pients wh suclinia CS assoced wh he recent onse o diabe es hypeenson oesiy o low one ss or nonnconing adenl masses i iging vors a enign esion epea radiogaphc evlu tion is recommended n o 6 onhs nd hen nnually 1 o yes Adenos usuly wi no gow more han c over onhs Moe pid growh shoud promp adenecomy Screenng r horona hypesecreon is repeaed annuly r years s in he re nstnce h he mss ecomes nc ion i is lkey o occ n the rs yers owing s ds cover A ecent sudy docuented subcinic CS on olow -up esing n appximey 8 o paens who were houh to have nonunconng denoms niti sceening
Adrenocoical Carcinoma
ACC is a re lignncy ecng 5 o 2 pesons pe lion pe ye h is oen ssoiaed wih he eessive poduion o aden hoones iens wi h ACC os equeny pe sen wih sgns and sypos eaed o hoonal eess They ay also epeiene sypos eaed o loc uo gowh adoinl ulness nuse o pain o es ss ACC s soees deeced incidenly when doinal iaging is peed anohe eason see nidenly Noed Adena Masses) Auonoous seceon o adena hoones o hei io logiy inive peusors s seen in oe hn o piens wih ACC oso 5 ulple hoones 2 andogens 5 o adoserone aey he pholog dagnosis o ACC is hlengng sch ha wh lows phology u lge uo size o oncernng iging ind ngs see Tle 9) close ineval adiogaphi low up is needed ae suge The pognoss o ACC s vey poo wih n ove ol iy e o 6 o 9 ngeen depends on he een o disese a pesenion pen surgal esecion is sline eamen ey disease Aduvn adohepy o he uo ed s used when reseon is inoplee Aduvan edia hepy wh ione n denolyi dug is reom ended paens wih nown or suspeed esidual or esai dsease Cyooi heoheapy hs poo ea n addion o ione inhios o denl seoidogenesis eyapone eoonzoe nd eoide ae used o tre CS pesen Sug ey esi ACC is ndiced i syp os eed o hoon hypeseeon nno e onoled wih edcal hepy aone eruan eous adioeuency laon ay so e used o ea unesece piay uos o easases when needed KEY POINT
• Adenocoa ainoa s aed y sgns and sypos eaed o hoona eess as we s syp os eed o oa uo gow h adona ness nausea o a pan o essis
Disorders of the Thyroid Gland
KEY POINTS
Thyroid Anatomy and Physology
• The wo an goas o evuaion o adena inden aos ae o iden adena asses ha ae ey o e aignan and hose ha ae assoaed wh hoo n hypeseeon so ha geed eaen an e undeen popy
n hehy aduls in he Unied Ses ech hyoid oe no ally esues up o 5 c n lengh 2 m in widh and 2 in deph he enie gnd weighs o 2 gas The ishus a hin nd o hyod ssue ha onnes he wo oes is to 4 m in hiness nd is ypialy no pape iuse hyoid disodes suh as lyphocy hyoidiis y esul in enlgemen o he shus o 5 o oe whih y e ppe nd give he cinicin he se sense ha he enie hyod s enged
• Aden asses ae age hn hose w h wosome adogph ndngs nd pheohoocy oas shoud e eoved suga
40
Disorders of the Thyroid Gland
There are two rms of active hyroid hormone: thyrox ne (T) and triiodothyronine (T/ Iodine is necessary r he rmaion of thyroid hormone. Deficiency may result in hypothyroidism. The hypothalamic-pitutary-thyroid axis responds to the subsequent horm one defcency by increasing thyroid-stimuating hormone (TSH) secreion, resultng in development of a goiter. Iodine is typically obtained through diet it s present in seaod, dairy products, and iodized sat Athough iodine deciency is a worldwide healh problem it is relatively rare in the United States with the incorporation of iodine into sa. Thyroid hormone production is conrolled by two man rces secreton of TSH (thyrotropin) and reguation of periphera conversion of T to T TSH release om the anerior piuita is stimuated by decreases in concentrations of serum T4 and T3 and secretion of thyroropinreleasing hormone (TRH) from he hypothalamus The T and T" in turn decrease secretion of SH om the anterior pituitary as par of a nega tive feedback loop Additionaly, T3 nhibis rther secreion of TRH om the hypothaamus Athough the hyroid gland produces boh T 3 and T he ratio of T4 to T 3 secreton is nearly 201 with most T (80%) resulting rom 5'-deiodnation of T1 in peripheral tissues. he vast majorit o both hormones are bound to circua ng protens including thyroxne-bnding globulin, trans thyrein, albumin, and lipoprotens The nction of hese proteins is to increase the circulatng poo of hormone by deaying clearance and maintaining a reservoir of hormone available r use. Ony a small percentage of toa crculating thyroid hormone is ee (unbound); hs action is readily available r celular uptake and determines the biologic aciv it of the hormone. 1
3
•
KEY POINT
• hyroid hormone production is controlled by two main rces: secretion of thyroid-stimulating hormone (thy rotropin) and regulation of peipheal conversion of hyroxine (T4) to triiodothyronine (
Evaluation of Thyroid Function n patients with an intact hypothalamcpituitary axis the initia laboratory test of hyroid activty is TSH measurement which is exquisitely senstive r detection of disorders of thy roid dysnction n patients r whom there is a high susp cion of thyroid or ptuitary dysfuncion, a concomitant thyroid hormone (T4 level should be assessed wih the TSH level to evauate r centra hypothyroidism he TSH level may reflect hpofuntion (i yfnon (low T) o no mal range The normal reference range r TSH is variable among laboratories bu is generally between 0 and µUmL (05 m U) and determinations of normal TSH evels shoud be made based on the eference range of the laboratory beng used. There are hree ve impotant exceptions to this general
range. uring pregnancy the range shfts lower and varies by trimester (see Thyroid Function and isease in Pregnancy). The second important excepion is n the elderly With agng, the rerence range shits higher; the upper limi of normal exends to 7 µUm (7 mU) in patients older than 70 years The third exception is in patients wih known pituitary dys nction or a ris of puitary dysfunction (history of cranial irradiatio piuitary sugery or massive head rauma) f the serum TSH eve is ankly abnorma additiona evaluaon of thyrod function should be consdered to deter mine the extent of the dysfunction. Ths is accomplished by measurng T when he TSH is eevaed and by measuring T and i when the TSH is suppressed. hen indcated by an abnormal TSH, the crculating leve of thyroid hormone should be assessed usng total or ee T 4 levels Tota is a reection o the bound and unbound rac tions of the hormone and is a reasonable method of assessing overal thyroid hormone levels n most patients. However in patients wth disorders of proten meabolism, such as kidney or lver disease, measuremen of ee T ensures a more accu rate representaion of the hormone concenrations Addtionally, condions that raise serum total proen evel such as in patients taking estrogen or during pregnancy, may result in a higher tota T concentraton and measuring he ree T is indicated The same rules appy to as o T regard ing proten levels bu ee T has a ve short hal life and evels uctuate more and are less reliable therere i is con troversial wheher toal or ree T 3 should be measured in patiens at risk r proein abnormaies. Measurement of serum T3 is necessary i the patent has a suppressed TSH eve because, n some patiens with thyro toxicosis T may be prerentially secreed over T (T toxico sis). In patents with an elevated TSH leve, indicaing hypohyroidism, measurement of serum 3 s not helpfu because it wil be maintained in the normal range even in those wth signcant dsease. Thyroid autoantibody measuement may be helpfu under cerain clinica circumstances n paiens with a persona history of autoimmune disease (such as type diabetes melitus, systemic lupus erythematosus or celiac disease) or a srong mly history of thyroid dysfuncion measuring thyroid autoanibodies may indicate he cause of the thyroid dysfunction or wheher a paien is at risk r developng thyrod autoimmune disease if the TSH is nor ma. There is no cinical indication r seral measurement of hyrod anibody titers to determne the need r or to guide therapy. There are three rms of thyroid autoanti bodies thyrod peroxidase (TO) thyrotropin receptor (TRAb and olobln (TAb Elvd ti of antibodies are associaed with autoimmune hypothyroid ism, or Hashimoo disease atients with TO antibodies and norma thyroid funcion tests are at an increased r sk of developing overt hyroid aure (2-4 per year). Thyrotropin receptor antibodies (TRAb) are divided ino three ypes: blocking (also called thyrotropin-binding 1
1
3
41
Disorders of the Thyroid Gland
nhibtoy mmunoglobuns), stimulang (also caled hyrodsmulatng mmunoglobuns or TS]) and nutal. The pesence of TS! autoantbodies is esponsble the dveopment of Gaves sas. TS autoantbodies should b measud autommune hyperhyodsm s suspected. Thyoglobulin Tg is a glycopotn located whn the co lod on whch thyroid homons ar synthsized and stored Sum Tg and TgAb masuements ae used to mono patients wth thyod cance; seum Tg s a highly senstiv and specfc maker o rsidual hyod ssu A tota thyodectomy and adoacve odine abaon, the pess tence of a dectable serum Tg s a possble ndcato of esdual or curnt dseas Thyrogobulin antbodies a pesent n up to 30% of paiens Thei pesence in the seum s only sgnan n pains wh hyoid canc as thy can lsly low he srum g Thre gAb ts shoud aways b assssed smultaneously wth th Tg f antbodes ae present the Tg level may no be elable. Calctonn sctd by the C cells of th thyod s most fquntly usd as a tumo makr n paents wth a hsory of mdullay thyd cacinoma. Seum calctonn lvs can hp ncease the sensvy of dtecton of mdulary hyod carcnoma when usd n conjunction wth nened aspa on FNA. Howvr is no rcommene as a scnng test n al patns wth thyoid nodules because it lacks the u st speccy. Instead masument of cacitonin should b consded f a patent wth thyo nodula dseas has a hs oy of hyppaathyoidsm o a mily histoy of mdullay hyo carcinoma o muip nocne noplasa yp 2 o f thee is clnical suspicon hes sodes Radoactv odne uptak RAU) is a measu of odn uptake by he thyod ove a p-spcfed tme ame ypi caly 4 hous RAJ s used to valuat the caus of hyprthy rodsm t s not indcat n patnts wth noma o levatd TSH lvls The ege of upa is usfu distngushng the vaious causs of hypethyoidsm RA pecentage s typcaly vey high in patnts wth Gavs dsease dusely inceasd uptak) and only modrately evatd n those wih toxc multnodula goter patchy upake in areas o noduls with relative suppsson of nomal tssue). n contast the RA s vey low n those wth thyrodts o exposure to exog enous thyod homone The pesence of a ·'cold" nodul on sotope scannng s an ndicaion ulasonogaphy to hep detmne FA is ndcad. s contandcaed duing pgnancy and whle basteng. KEY POINTS
• The ntal laboatoy test of thyod actvy s thyod stmulatng homone measuement n patents wth an ntact anteo ptutay measuement of thyod stmulatng homone s exustely senstve detection of dsodes of thyod hypouncton hgh thyodstmulatng homone) and hypefuncon (low thyodstmulatng homone). (Continued)
42
KEY PO N S
(continued)
• f cental hypothyodsm s suspected, a concomtant thyod homone thyoxne [T ]) level shoud be assessed n conjuncton wth the thyodstmulatng homone level. 4
• f the thyodstmulatng homone level s anly abnomal, addtona evaluaton of thyod funcon should be consdeed to detemne the extent of the dysncton measue thyoxne T 4 when the thyod stmulatng homone s elevated and measue both hyoxne (T, and todothyonne ) when the thyodstmulatng homone s suppessed
HVC
• Thee s no clncal ndcaton seal measuement of thyod antbody ttes to detemne the need o to gude theapy except to monto esdual dsease n patents teated thyod cance
HVC
• Radoactve iodne uptake s a measue of odne uptake by the hyod ove hous t s used to evaluate the cause of hypethyodsm and s not ndcated n patents wth nomal o elevated thyodstmuatng homone levels.
HVC
Funcional Thyroid Disorders Thyrotoxicosis Evaluation
Thyooxicoss is a tm used to descb thyo homon xcss fm all sources wheas hypethyrosm is the moe specc tm to descib thyoid gland overactvty Thyotoxcoss may resut rom endogenous thyod dsodes ptutay tumos and xogenous levothyoxn The most common causs o hyprthyrodsm a Gaves dseas and toxic adnoma(s) The symptoms of thyotoxcoss nclude heat intoerance, palpatons dyspna, temulousness mnsrual gula s hypedfcaon weght loss inceased appetie pox mal muscl weaness tgu insomna and mood distubances The sevety of sympoms may not coelae wh th leve o thyod homone deangment. n older patents many of the classc symptoms of thyrod homone excss may be absent and the only pesentng symptom may be atal brilaton o hea lue ths s known as apatheic hype thyodsm v / symptoms o thyotoxcoss shoud be measument of seum TS alone llowd by measuemnt of T and T levels f TSH s suppressed The ypcal patte of hypethy odsm s TSH suppesson wth an elevated T ando T A nomal seum TSH in the setng of an elevated 1 ando T 3 concnaton suggests the pesence of a TSHsecng pu itay adenoma these umos ae extemey ae and ae managd dently fom oth causes of thyotoxcoss (se ate dscusson)
1
3
•
Disorders of the Thyroid Gland
KEY POINT
• e pa paen o abooy sues n ypeys s ysuang oone suppesson w an eevae yne ( 4) an/o ooyonne 3) eve
c Mangement
Athog he specic ntevon use s saly detemie by e uerlyng cause ad aient ad physicia erenc contol of he yroic stae ay be chiev by o o hree reaten oalities: onades adioave odne aba o or surgey. Rapd conl of adreergc sympos w a � bocker s nicae i mos patients w yotoicosis lhoug anolo is freqenly sd r is addd c o ibition of erpea coversio o T, o T,. cardoselective �bocker s sch as aenolol, are eferre owg o aditiona bees o ecrease cer evos syse se efcts an mprved aheece w onceday dosn Methimaoe and pyliourcl PT are te wo hoaes avaabe in e Ue Sas Meiaoe is the preeed agent because has a hier tayroia reeion (oency a preabe osn egn tyicaly oce daly an a reduced seec e tyrd edicatons rede T ad evels wii a fe ays o niiao bt e ul eet ay ake sevel ws Nomazao o a pev ousy supressed TSH eve ay ake several ons I s cica ter ee o moitor 1 ad levels drng teaen o ypehyois becase e TS ay o be an accrae reecon of he yrodal stas. oamies ay be used o eae aties ty rodecomy o radooie eaen or tey a be sed as e piary hepy Thioamies may be sed 1 o 2 yeas n atents wi rves dsease in h oe of achievin emisson more detve therapy w adioacve iodine or sre may e be sog aer a imerae ypey oidism ersiss log honades ae geeally we oeaed i is portat o be miiar w ther sideeffec ole. The ost commo reacon o antyrd media ios s a rash seen p o 10% of paens. Adionay PT may case elevatons o aminoransas eves Rare cases of faal hepaotocy have bee descrbed w PT Theefoe is use s eseved r paets ho canno toerae meth a ole ad i e rs reser o pegancy, when ei aole has a possble eraogeic e ct cholesac pan of liver tes abnormaies may also be see with ethimazoe b it is tyay teoary and milde than a sen with PTU Boh dgs may be assocae w reversbe agano cyoss in arately in 500 paet s Baseine iver ces sues and complee bood count wit difenta ae ecommened bee niaon of atithyroid eca os wh sera monoing o he coete boo cou duig theapy patiens akg a toname deveop a ve as sevee sore hoa janice or other spos of
serios ess hey should be assessed ompty a adverse reaction o e medicon Te goa of radioactve odine abaon s to rende he paen yoh yod, wch ca typicaly be accompise in 90% o paens w e s eamet lthou a inoy o atients may develo ac antior nc ai r raa on yroidts radoactive one ablation s tycay wel oeaed I may take sevel onths r the developen of ypotyrodism, so t s mporan o onito thyoi unction ess only aer therapy a aient wth sevee h yroo coss, adoacve odie ay provde adional sbsae o th hyernctionn gand. eslg i eacebation o e ypehyroid stae Conseey. t may b reasonabe o ntiae a thionamide io o ablaion o lower the tyroid ho one evels Sey s ey r sie they gve e inhere risks it any sgery. Paients who coo cano be acieve w tionaides an thos who are no coable w radioiodine theay are typically eed sery Becase o the iased nrathyoidal vasculariy e oceue can be techncall ore dcl a a tyica yid ectomy. Aditionaly rsoron of te ehyro sate bee surey wit oades is poran o mve emoy namis drn eneal ansesia ad decease the paents is of yd sor c KEY PONT
• ono o ypeys ay e aeve by one o ee eaen oaes onaes oave one abaon o sugey; oa oe epens on e uneyng ause an paen peene Grves Disease
Gaves disease s a uogan syse auoune soe ha can ac he hyoid eyes and sn s equeny seen in woen beween he ages o0 an O yeas an is e os oon cause o hyehyods n he Une Saes. Anboes agains he TS eeor TS! o Tb suae auonoous poucon o T and T Paiens eueny epo a my hsoy o Gaves dsease asoo yrois o ohe auoiune ondions n hysca examnao paens have eevae sysoc bood pessue wi a wiene pulse pessue ahy ardia an a usey enaged hyo Fuer ns peon o te yoi ay eveal a bui. are exanaon o he skn ay evea peba yxedea an iniaive poess ha s ypicay pay wth a peau 'onge appeaane o he s Diagnoss o Gaves isease is ade liniaLy n os insances an easueen o TS! anbodes is eseve patiens who ae no aredy hyoxi o exanaon an o no ave a cassc smoo rubbery duse goe n hose paens S aiboies may hep eerine e ause o he hypeyois AU a san wl show aedy nease upae wi use avy on e san 1
3
•
43
Disordes of the Thyoid Gland
Cental Hypethyoiism TSH-secreting pituitay adenomas are extremely rae. In this conditon, serumTSH serumTSH is detectable or normal in the setting of an elevatedT4 and/or T3 concentration A dedicated pituitay MR wil demonstrate demonstrate an adenoma.Treatment Treatment should cus on emova of the pitutary tumor; thyroidtargeted therapy is ineective (see Dsorders of the Pituitary Gand). Subclinical Hypethyoism Subclincal hypethyrodsm is a aboratoybased dagnoss defined as the presence of a suppressedTSH suppressedTSH level with noma T and andT T levels. Repeat assessment of thyroid thyroi d nction should be perrmed 6 to 12 weeks after the nita tests as the values wil normaize normai ze in up to 30% of patents Symptoms of o f thyo toxicoss are typcaly mld; most patients are asymptomatc Which patients will benet most fom normaliation of theTSH the TSH level is not universaly agreed on but consensus opin ion recommends treatment r patien patients ts with aTSH aTSH level beow 0.1 µ/mL (01 mU/The benets of teatment te atment r r asympto matic patiens wth aTSH aTSH level between 0.1 µ/m (0 m) m ) and the lowe lmit of the norma referene refe rene range are less clear Emerging data suggest that chonic subcinical hyperthyroid sm has a negative eect on cardiac nction the central nev ous system and bone mass. The risk of atrial brilation is sgnicantly inceased when theTSH theTSH level is beow 0.3 µU/m (0.3 mU/) so patients over the age of 65 years and those wth a history of coronary artey disease or tachyarrhythmias as we as patients with osteoporosis may benefit om normal zation of theTSH theTSH level. Radioiodne is the prefeed treatment bu oten the gland does no have sucent iodine avidity and methimazoe must be used KEY POINTS
HVC
• In patients with subclinical hyperthyoidsm repeat r epeat assessment of thyoid nction shoud be permed 6 to 12 weeks aer the inta tests as the vaues wil nor mae n up to 30% of patents. • Treatment r subclinical hyperthyroidsm is recom mended when the thyoidstimuating hormone eve is ess han 01 U/m (01 U/L)
Trd r Df Hypothyoism Evaluation
Hypothyroidism refes to low crculatng thyroid hormone levels. Hypothyroidism is moe prevalent in women than men (2% versus 0.%) and in those with othe autoimmune dis eases The most equent cause is Hashimoto thyroidtis also known as chronc lymphocyc hyrods. atrogenic causes incude surge radoiodne rado iodne therap and extena beam radia tion theapy to the neck. Hypothyoidism may also be medica tion induced; the most common causative agents include lithum amiodaone interrons, interleukin2 and tyrosine knase nhibitors Raely, pituitary tumors severe head
trauma ptuitary surgery or cranial radiation can cause cen tal hypothyoidsm The clnical manfestatons of hypothyroidism include tigue cold intolerance constpation heavy menses, weight gan mpaired concentration dry sn edema depresson, mood changes muscle cramps myalgia and reduced fetiity The physical examination findings may incude reduction in basa temperature diastolic hypertension badycardia dry skin brite hai hoarseness delayed reaxaon phase o the deep tendon eexs and an enlarged thyrod An elevated serum TSH level ndicates the diagnosis of pmary hypothyroidism. n patents with an elevated TSH that is ess than 10 µU/m (10 m/) a low seum seumT T measure ment is helpul as a anky low vae indcates that thyroid hormone replacement s necessaryThe presence ofTPO anti bodies suggests that Hashimoto thyroidtis s the undeying cause.Thyroid cause. Thyroid imaging is not ndicated unless there ther e is concern r a nodule nodul e on physical examnation 4
KEY POINTS
• An eevated serum thyroidstimulatng thyroidstim ulatng homone level indicates the diagnosis of primay hypothyoidism; thy rod imaging is not indcated uness thee s concern r a nodule on pysica examination examination
HVC
• The most euent cause of primary hypothyrodism is Hashmoto throditis (chronc lymphocytic thyrodi tis) the presence ofTPO antibodes is suggestive of Hashimoto Hashimo to thyroiditis Managemen
n patients with aTSH aTSH level greater than 0 µU/m (10 mU/L, daily thyroid homone replacement is recommended. Thyroid hormone replacement with evothyoxine alone s recommended. The goal of thyroid hormone replacement theapy is normaliation of the TSH. The stating dose can ca n be weightbased at 1.67 µg/kg/d usin usingg ideal bod bodyy weig weight. ht. In patients with prevalent cardiac dsease, tachyarrhythmias, or mutiple comorbidities, or in those who are older than 65 years the dose shoud not be based on weight but ather shoud be 25 to µg/d.The µg/d.The dose shoud be titrated based on TSH eves measued 6 o 8 weeks ae any dose chan change. ge. To mprove gastrointestinal absoption levothyroxine should be taken on an empty stomach 1 hou bere or to 3 hours after ngestion of od or medcations that would interfee with absorpton such as calcum or ironcontaning suppements. Patients with celiac disease may reure higher levothyoxine doses because of mpared absoption. There has been signicant debate egarding the need supplementation of T iothyronine in patients with hypo hyroidism The shor hali of T triggers acute spikes in seum T eves whch ae o signicant concen ederly patients or those with preexistng preexist ng cardiac issues. Additionaly Additionaly numerous studies have iled to show a clear benet o f aT aTT combination ove T aone; theree this is not generaly recommended. 3
3
3
3
4
45
Disorders of the Tyroid Gland
KEY POINT
3
• In patients with a thyroid-stimuating hormone level greater than 10 µU/mL (10 mUL), daily thyroid hor mone replacemen is recommended and shoud be taken on an empty stomach; he dose should be titrated based on thyroid-stimulating hormone levels measures 6 to 8 weeks aer any dose change. Subclnical Hypothyroidism
Subclinica hypothyroidism is dened as an eevated serum TS evel with a norma level. he poenial caues are the same as r over hypohyroidism. Repeat measuremen of the S level is recommended, particularly in an asympo matic patient, as it wi wi normaize in up to 30% of patients by 6 weeks. Patiens typicaly have mild or no sympoms of hypohy roidism. Subcinical hypothyroidism may be associated wih severa laboratory abnormalities including elevated total cho lesterol LDL cholesterol, and C-reactive protein leves. Large studies sugges that hese aboratoy abnormalities ranslate into an increased risk of atheroscerosis and cardiac events. owever supplementaion with levohyroxine has not been shown to mitigate this risk. reament is generally recom mended r hose wih a S level greater than 10 µU/m 10 m/ but levothyroxine treament should be considered in patiens who have posiive TPO antibodies or a large goiter as these patients are at risk r r progression to ove hypothy roidism at ates of 3% to 8% per year. A goa TS evel less than or equal to 25 /mL 25 mU/L is ecommended r women with subclinical hypothyoidism and posive P antibody status who are planning to conceive. 4
KEY POINT
H
• In patients with suspected subclinical hypothyroidism repeat measurement of he thyroidstimulating hor mone eve is recommended recommended as it wi normalie in up to 30% of paiens by 6 week s Drug-Induced Thyroid Dysfunction Vaious medications can aect thyoid unction and are isted in Table based on their mechanism o action. Amiodarone may have a potentialy toxic ect on the thyroid. The iodine conten of amiodarone is 37% by weight. It is sored in t, myocardium iver, lung and thyroid issues, with a ha ha ie ie exceeding das his ong half-lie coupled with the high iodine conten, renders it a potentialy oxic compound to the hyroid. The two types of amiodarone hy roid toxicity are changes in thyroid function studies seen in all patients obligatory eects) and those seen in only a subset of patients (cultatve eects). he obligatory ects resul fom he increased circulat ng iodine ater iniiation of the drug daptaton to the acute iodine excess causes a reduction in organfication o iodine and reduced producion o thyroid hormone Wol haiko f
4
eect). The result is a temporary reduction in circulaing T and T evels with a minor rise in the S level; these changes typically reverse within he rst 3 monhs of reament and require no inevention. Facultative eecs, seen in up to 1% of patiens, may cause either hypo- or hyperthyroidism In areas of iodine iodine suf ciency, hypothyroidism is the more common oxicity. Those at highest risk are women with preexisting TPO antibody positivty Amiodarone-induced thyrotoxicosis (AIT) is moe commonly seen n maes and in those iving in iodine-de cient areas Type AIT is the resut of exposure o excess iodine and occurs in hose with preexisting thyroid conditions, such as atent Graves disease or nodular goiter, in which the iodine increases nregulaed thyroid hormone production. ype 2 AIT is the result of the cytotoxic eects o amiodarone on thy roid tissue producing a clinica picure of painless thyroiditis with abnormal release relea se of hyroid hormone. The treatments dir with each type but distinguishing between the wo rms of AI often can be challenging and may require the aid of an endocrinoogist he time to recovery of normal thyrod function may be several months, even with prompt diagnosis and reatment. iscontinuation o amiodarone is typically necessary paricularly in those paiens with type 1 AI
KEY POINTS
• In the majority of patients amiodaone causes a tempo rary reduction in circulating triiodothyronine triiodothyronine T and a nd thyroxine ( and levels with a minor rise in the thy roid-stimulating hormone that reverses within rst 3 months of treatment t reatment and equres no interventon • In 5% of patients amiodarone may cause either hypo or hyperthyroidism; hyperthyroidism; those at highest risk r amiodaroneinduced amiodaronein duced hypothyroidism are women with preexisting thyroid peroxidase antibody positiviy.
Thyroid Function and Disease in Pregnancy gnficant changes in thyroid nction occur during preg nancy understanding understan ding the normal physiolo during gestation is critical r a correc inerpretation o thyroid laboratory studies. Abnormaliies o thyroid unction can have a dramatic ect on he heath of the moher and the feus. diagram of the physioogic changes in thyroid function during each tri mester is shown in Figre 8. Increased estrogen levels cause a rise in hyroxinebind ing globuin. To maintain a stable ee T and T thyrid hor mone production is increased and remains within the norma reference range the patient's trimester (see later discussion r trimester specfic anges). anges). outine screening of is not indicated r every pregnant woman. screening is indicated in women with a isk of thyroid gand dysnc tion including those already on thyroid hormone replacement therapy; those with autoimmune disorders, goiter previous
3
,
Disorders of the Thyoid Gland
TABLE 26.
Medcatons hat Aect hyrod Functon
Mechanism of Acon
ug
Commen
Decreased aborption or enerohepatic circulao
Calcm
t is recomeded at levohyroxine ingestio be eparaed fro ee medicaos by seveal hou
Poo pmp inhibitos Iron Choletyraie Aumm hydroxide Soybean oil Scralate Psylliu
Iceased metabos of evothyoxe
eyo abamazepe
Hge levoyroxe doe may be equed o maa evothyroxine e oal age
Rifap eobabia Serae Thyroiditis
Amiodaoe
May cause hypo- or hyperyrods
Lithiu Iereo afa lerlek-2 yroe kae ibtor De ovo developme of antyod abodes
Ierero alfa
nhibio ofSH ynthesi or eease
Gucocoticods
May deveop asoto yods, Gave dease, or pale yod
Dopamine Dobutae Octreode
creaed hyoxe-biding globu
Esoge Taoxfe
Fase elevao of oal T 3 toa T 4 evels; free T 3 4 ay be more accae efection of homoe eve
Meadoe Deceased thyroxinebnding globul
Adoge theapy Gucocortcoid
ase lowerg of toal T , total T 4 evels free T , T 4 ay be more accuate efection of hormoe evel
Niac T3 = triiodothyronie; T4 = trxin TSH = trid-stimulatng hormon.
head/neck irradiaton, previus hyrd surgery knwn posi ve TPO anibodies r posive TS! antbdies o a srong m ily hisry f hyrid dysncion; those who ive n idine-decien areas r hose lder han 30 years. In paiens n evhyroxne replacemen he dse of he medcaion may need o be ncreased n aveae by 30% 50% and µaens shld have their TSH level cheked as soon as a pregnancy µv Feal hyrod ssue s no fncnal nl 10 12 weeks' gesaon necessang maeal thyroid hormone ansr hrough he placenta Thyrod hormne deciency can nega vey at al nercognve developmen I s criical manain a euhyrid sae dring pregnany n hese paients TH testng shuld be perrmed evey 6 weeks hghu
pegnancy wh adjusmens in thyrid homne eplacemen osing as neee to mainan he TSH whin he trimeser sµec nomal range The lages dose escalaons ypcally ccr n he rs rmeste with more dse stabiy laer n pegnanc Dagnosng possible hyperthyrodism durng pregnancy may be chalengng becase some physlgc hanges dring l h h h as achyadia ige and hea inlerance Serum TSH and hman chrinc gnadropn have a cmmn -sbn allown rssreactvy a the TSH recepor Cnsequenly TSH declnes dung he s rmeser he reference range shifs down o 0 5 UmL (0035 mU/) Dr n he secnd and hird mesers he pper lm f SH rses t
47
Disorders of the Thyod Gland
prubato h hypthaamcpuitaryhyro HT as ha u i up 7Y ptalze paets.he uderlyg au e crca e a nuence th pae o tyri 'u abrai Drus t are equely used i r t a pant n a a igca efc he P ax see Tab 2) pa pate s tally a wT ev lowed a heT el A t pate bes e crt hTSH ve a ao dee.eatn a a pc u a e cea hhdsm arTS a e eleaed ESS Two ea guidelne ar mprtant i eaua a r a pa Fr masue TSH ane ud b ba e s a g ca spcio th dyu ' S abra prvul descrb ro da atal laba ue shoud b we. TS ga tha 20µU/1011/L r s udeabe S le ey be e cause ad rt tyrd u u b red eTS bwe hes w vaues.rca ue a eamnai are v p a r t pas wth tr hr yto e ha ge t hospia rd u abr 1a a p eeral wee pa patte a 1 vaTS e an sghl w andT eves I a ay euthy pate hrod funcn tes uld be pa 6 w ae paz er y y h pstn TS abnomay r ESS wt nrmzat TSI c I
1
Week
10
20
30
40
8 G = ; 4 = BG =
FIGURE
3.0 µU/mL (3.0 m/ An addtonal complating cor s that rdioodine scnng is ontraindcated ding preg nancy becuse of the risk r etl tyroid exposure o diton. nsted, seveal nical clues my b used to help determine f he patin as yrotoxicosis, inluding he prs ece of a goiter, ophthmopay or S! ntbodes all of wich are suggesve f ravs disae. he use of honmids is considerd sfe duing prgnancy, but PU s prered during the frs rmeser beause f potental tratogenc ects fro metimazole durng rganogeness Altugh rarey indicaed surgery my b perrmed durg the secnd trmester. It sould be reserved r those who are unable to tolert honamdes r who ave adeque control n medl herapy Radoodine terapy is cntraindicated during pregnncy and whle bresteding. reatmen gols with tonamides are a detectable S in te lower end he prgay rerece rage d a ee te upper end of he rerence range. KY PONT
• In pregnnt ptients on levothyroxine replcemet te doe y need to be increed on vere by 0% to 50% pients sould hve teir thyroidsimuting hormone evel checked s soon s pregancy test is positive
Cl Euthyroid Sick Syndrome : S) a e e T a ·aru ha a b ad O h u ru J l h a u ere a a 48
i
KY PONTS
• ritic illness cn cuse chnges in thyroid functio tests in up to 5% of hospitlied ptients known s euthyroid sick syndrme mesurement fS should only be obtined in te hospitl when tee is hig clinicl suspicion of thyroid dysction • he tpicl pttern of euyoid sick syndrome nothy roidl lness syndome or low riiodothyronine syndrome is midy eevted thyroidstimutn hor moe leve nd slighty low thyroxine nd triodo thyronine ( evels. • Aer pients it eutoid sick ndome re dischrged om the hospit hoid ction bnormities my per sis for severl weeks so low up thoid ctio tests should not be repeted un6 weeks er dischrge
VC
3
Thyroid Emergenies s y ae n gen. yrod a ema a rpet tue a e s ur cra a Faur mae a l danss a u eame aa wh a h ay ae Thyroid Storm yd r a eer aa t w hreag a dpea )
VC
C
Disorders of the Thyroid Gland
C The cadina eaures dagnoss include evtd empe CONT.
tue signicant achycarda heat ue. gasnestinl dys ncon · (nasea, vomtg, aea nd/o Junce) and neologic dist bances The ane o centa ne ous syse manifesaions incdes inceasing gttion eona !abi y consion, paanoia psychosis or coa Altog yoid storm has been epoted wit any cuses o thyoxicoss occs most commonly wi Gves dsase Tyid storm may be pecipitated by anohe event suc as nction suge myocardi inrction. taua or patrtion Adminstrion o docive odine terpy to a patien wt uned o unconroed yperthyoidism can rige tyoid so The dagnoss is based on cinica pr esenaton bu cn genealy be red o f T nd eves e win nora lmits Teatmen o tyoid so soud be dieced ord edcon of yod hoone prducon. decreasing pephe conveson o o T addressn denec sympoms nd hemoeglatoy chnges, seacn or and eting precipi ing ctos and evesng systec dec opensation Thonaides and � bocers ae te instay o reamen o edce hyoid hormone podcon and con adenerc symptos PTU and ppanoo e he peed agens becase they have te added bene oblocing peipea con veson o T o Addtionaly idose glucocortcoids edce T conveson o bocve T A east hou ater te rst dose of a honade. odne dps sould be adinsteed to inibi fuher eease o hyd oone o te gand Aceamnopen and coolng blankets y be used to cono te ypethemia owever even h agessive hepy nd sup potive esres moality ates ae as as 5 to 20'7 C v
I
4
3
1
1
3
•
KEY POINTS
• Thyod som s a seee manesaon o hyooicosis h eheaenng seconday sysec decopensaion (shoc; occs mos commonl ih ndelyig es dsease copled h a pecpaing co sch as neco sge myocadal nacion o paion and moal s % o 0% • In addon o sppoe ce and eaing he paic pang case honamdes ad �bloces ae he main say of eamen o edce hyoid homone podcon and ae oe combned h iodine dops and high dose glcococods o ea hyoid som Coma C Myxedema Myedem coma s an extreme b rre nieston o ypo
h yroidism esling in liehr eatening secondy sysem decopenstion Wiout anky low eve. yxede coma s uniely egardless o the degree o TSH elevton 1 has vey high moalty ae f here is delay n tement Myedema coa is more comon n eldely woen: may occu in ose wih a istoy o hypotyridsm or no an tecedent llness ecipiating events are equent, such s myo cadil inction iecion sroke rau gstrinesna I
r
bleedin or metbolc dernnts Cold posre pprs to be rs cto s s condn s o coony seen n the ner ons ena saus chnes nd ypotheri re the os coon cincl mn sions he specr o ental s us chnes includes eha supo coa. depession or even psycosis Hypoera eperue ess n 344 °C [94.0 F]) s presen n ry pins oe teperres re ssoced wt se pnoss Venory dive s deceased esuing n ypoxema nl ypecpn Addion sns inclde bdycad ypog ycei. yponr ea. nd or ypoenson A sincn pecene o paens experence seizes wic my be relaed o e coexsn e bolc derangeens yxee com s suspeced ser H nd T levels should be esed ede Dignosis s me bsed on he clnicl presenaion nd e coexsin ebolic bnolties h sem corisol evel soud be checed as soon s possbe o evauae r concon dena nsu ciency pro to ntiaion o yid homone epcemen Whi waing he rsults o e se coso easueen. s enerly advsble o epiicly in dose luco cortcoid terap is erpy y be dscontnued i te serm cotso eve is und to b nora or hig rmen o1yxede coma s aed t estoon o the euyid ste wh tyrd or1one py suppo ive cae echanica venition vsopressos nd lucococods) wr11e ntvenous uids wing blanets. nd anagemen o e uneryng precipiatng event he exact ose and preption o yrid horone o dnster s conoversi minm cinicl ra rtion s vlble to ascetan e opa n eg1n s iportan o balance te need r rapd ensteen o a euhyrl state w he isk o precpng l crdac evnt de o incresed crdc work wi dnsron o hyrd ormone ee y. nrvnous levothyoxine eapy s d n iser ed inly s an nvenos bous o 200 o 00 µg oowed by iy oses o O o 0 µ rven ous y unl tnsiion o n orl muion s easb reamen w T s no recoended Even wh gessive epy the moy te or 11yx ede coa is 0Y o 2 C 1
KEY PONTS
Myedema coma is an eeme b ae maniesaion of hypohyoidism resling in ifeheaening second ay sysec decompensaion and a moaliy ae of 0% o % • The eame of myeema coma is amed a esoon of he ehyoi sae wih hyod homone heap sppoive cae mechancal enlaon asopessos and glcococods amed inaenos ds ang blankes and managemen of he delyng pecipiaing even 49
Disordes of the Thyod Gland
Structural Disorders of the Thyroid Gland Thyroid Nodules Nodulariy of he hyrod is extemely common; arge popula on sudes sugges ha up to 5% o women and 1% o men have a clncaly evden nodue. The prevaence ncreases wh age. In auopsy seies and screenng ulrasound sudes , nod ues may be seen n up o 60%. he dieenal dagnoss r a nodule n he hyrod s vared and ncludes boh prmay hyrd disorders and mea sac spread om oher prmary magnances (Table 27) Mos hyrod nodues are bengn wh only approxmaely 0% haborng a malgnancy. Ulrasonography s an nexpensve and highy eecve method r sracaion o malgnancy rsk. All paens wh a suspeced hyod ndule should have
TABLE 27. pes oo Nous g
Mg
Multinodlar goite (cooid adenoma)
Paillay tyod cancer
Hashimoo choc yphocyc hyods
ocuar hyod cancer
Coloid cyst
Meday thyrod cnc
emorrhagc cyst
Aalas hyod ace
Follcar adenoma
may thyroid ymhoa
Hhe ce adeoma
Measa cnc Breast Meanoa Real cell
a neck ulrasound ha ncludes evauaon o he hyrod and cevcal lymph nodes. odules are equeny deeced ncdenally on magng sdes perrmed r ohe easons he dagnosc evaluaon o ncdenaly dscoveed hyrod nodules s idencal o hose ha are clncally deeced wh he same rae o malgnancy. odues ncdenally dened on luorodeoxygucose-PE (FOGPE scanning however have a malignancy rae o30% o 50% Consequenly Oavd nodules und on P scans requre heghened suspcon and a lower hreshold r ne venon or dagnosc evaluaon. A carel hsoy shoud be perrmed n paens wh a hyrod nodule ncreased rsk o malgnancy s und n paiens wh hsoy o adaion exposure o he head or neck a mly hsory of hyoid cancer o a personal hsory o hyrod cancer. Addona acors ha increase he rsk r magnancy n a nodue ncude male sex exre mes o age (<0 or >60 years rapid nodue growh and hoarseness. n phys ca examnaon he nodule should be assessed exure mobly, and assocaed lymphadenopah If he nodule s hard fxe d o suroundng ssue nonmoble wh swalow ng and/or here s assocaed cevcal ymphadenopah he rsk o magnancy s greaer Pan s an uncommon ndng wh hyod nodules bu when pesen s usualy assocaed wh bengn condions. A serum SH measuremen s he na aboraory es n a paen wh a hyd nodule. I he SH s suppressed measuremen o 4 and 3 shoud be errmed and a rado nuclde scan should be consdered Figr 9 he objecve o he scan s o den "ho or nconing nodues whch have a vey ow lkelhood o malgnancy and typcaly do no requre A. n conras i he SH s hgh or normal he adonuclde scan s unnecessay as i s unlkey o reveal a ho
History, physical TSH
Hgh or normal TS
Low TSH
Ultrasound
Thyroi scan FT T
>1 cm Evaluate for US-uieFNA
< cm Repeat US n 624 months
.1� Functionin "Hot"
Nonfnctionin Col/wam
NoFNA Treat hyperhyrosm
valuat or USuie NA
FIGURE 9. Initial evauation of a thyroid nodle. Thee ae size thesholds o F NA based on US apeaace A ess suspios lesion may not eed A u nt s age ha 2 m, ssos oles lage ha 1 m NA = ie-eee asiaion; F3 = ee oothyoie; F 4 ee hyoxie SH = hyodstmulaing homoe US= tasond
50
isordes of the Thyod Gland
nodule; the evaluaton should poceed with an ultasound and possble FNA. As thyod nodula dsease can be alteed by nomalzation of the TSH ultasound andFNA should be post poned n patents wth elevated TSH untl TSH s nomal, unless thee s maked concen malgnancy One-time measuement of thyod antbodes may be appopiate if autommune thyod dsease s suspected o f mutnodua gote s dentfed by ultasound to stat the patent's futue rsk of developng overt thyod lue Serum thyoglobuln measuemen s no useful and s not recommended. FNA pemed unde ultasound gudance s the opt mal test to detemne whethe a nodule is malgnant. When pemed by an expeenced clncan FNA s safe and ea tvely smple to pem. The senstivty ofFNA cytolo s 90% to 95% and the lsenegatve ate s 3% to %. NA of a nodule s geneally ecommended those nodules lage than 1 cm that ae sold and hypoechoc. The theshold FA of nod ules that ae patialy cystic and lacking suspicous ultasound featues s 2 cm n sze o greate Aspratng a nodule of mm o more may e consdered f a paent has sk ctos such as a pesona o my hstoy of thyod cance o po ada tion exposue. The sonogaphc appeaance of a nodule may be used to assess the sk of malgnancy and theeby gude the decson of whch nodules eque biopsy Featues concening malg nancy nclude micocalcfcations maked hypoechogenciy egula bodes and tallethanwde shape. Such ndngs ae nealy 70% specfc cance but thei poo senstvty cannot exclude the pesence of malignancy he vaous dagnoses obtaned on FNA and the assoc ated rsks of magnancy ae lsted n Table 8.
ABLE 28. Dge Obe b Fe-Neee p Nule Rsk Mlgac NA agss
Rs fo Magay
Mgeme
Beig
<3
Serial utasod examinatos or goh
Aypia of ceai sgficace/foclar eso o cetain sgficace
5-1
Repeat FNA
Sspcios fo ollca leso
23
Hemityrodectoy
Sspcios or malgacy
5-5
Hemtyrodectoy or total tyrodectoy
Malgat
91
Tota tyrodectomy
odo
0%-50%
; wo odiagostic NAs, srge
Modifed om: Cibas ES. Al SZ; NCI Thyroid FA State of te Science ofeee The Bethesd System o Repoig Thyoid yoptology Am J i Ptol 2009 Nov 13(5)658-65 [PMD: 9846805]
FNA = fine.eedle aspirato
Nodules that ae bengn byFNA should be llowed wth epeat utasound examnaton n 6 to 1 months to assess sgncant changes. f the nodule s stabe on epeat imaging and acks suspicious feates clnical examination and epeat ultasound can be extended to onge ntevals such as 3 to S yeas Geate than O% change n nodue voume o nteval deveopment of concenng ultasound chaactestcs should pompt a epeat FNA to evaluate a lse-negatve ntal bops Malgnan nodues and hose that ae suspcous r malgnancy eque pompt excson ths s typcly done wth total thyodectomy but hemthyodectomy may be pefeable patents younge than 45 yeas of age wth a tumo smae than 4 cm A nondagnostic FNA waants a epeat attempt. n a sod nodule with two unsatisctoy bop ses dagnostc hemithyodectomy s ndicated. Sugca complcatons ncude hypopaathyodsm and ecuent ayngeal neve paess although typcaly tempoay ethe compcaton may be pemanent in up to 3% of patents. KY PIS
• Thyod nodules ae und n 1 % to 5% of the popula ton; most thyod nodules ae bengn wth only appoxmately 10% habong a malgnanc. • A seum thyodstmulatng homone measuement is the ntial laboatoy test in a patent wh a thyod nodule f the thyodstmulatng homone s sup pessed then measuement of thyoxne ( ) and to dothyonne T 3) should be pemed and a adonu clde scan should be consdeed to dent "hot o unctonng nodules whch have a vey low lkehood of malgnancy and typically do not equie neneedle aspaton.
VC
• f the thyodstmulatng homone level s high o no ma! the adionuclide scan is unnecessay as t s unkely to evea a hot nodue and ultasonogphy s an nexpensve and highy eectve method stat caton of malignancy isk nonfunctonng thyod nodules.
VC
• Fneneedle aspraon of a nodule s genealy recom mended those nodules lage than 1 cm (0.4 in) that ae sold and hypoechoc and s the optmal test to detemne whethe a nodule s malgnant Goiters Mulndua
Mutnodula gotes occu moe equenty wth advancng age low odne intake o Hashjmoto dsease The sk malgnancy is he same multpe nodues as it is a sol ay nodue therere the evaluaton and management ae identcal. Bopsy should be pemed on the thee o u nodues lage than 1 cm with the most suspcous ulta sound featues In the absence of suspcous featues, the lag est nodules shoud be chosen aspaton 51
Disorders of the Thyroid Gland
A large mulinoduar goiter may be associated with com pressive symptoms such as dysphagia, hoarseness or posi tonal dyspnea. To assess the exten of mass efect addtiona esng and imaging including noncontrat CT of he neck/ chest barium swalow direct Jayngoscopy, and/or spiromery wth fo-volume loops, may be ndicated Levothyoxne therapy to suppress TSH secretion and reduce goie size s generally not helpul, poses a isk of thyooxicosis and is not recommended Radioactive iodine ablation is not an option r euhyroid and hypothyroid patiens Surgical removal is the reatment of choice f the compressve sympoms are signfi can, f malgnancy is suspeced or if the patient desires cos metic intervenon. KEY POINTS
• In patients wih a mulnodular goiter, the isk r malignancy is the same multiple nodules as t is r a solitary nodue; therere the evaluation and manage ment are identical • Surgical remova of a large mutinodular goier is he treatment of choice if the compressive symptoms are significant if malignanc is suspected, or if the patient desires cosmetic intervenion. Simple Goiter
A smpe goiter is defined as an enlargemen of the thyroid gand wihout the presence of nodues. I may be seen in conditions of dyshormonogeness autoimmune thyroid dis ease or primary hyroid lymphoma. Primary yroid lym phoma is a rare condition tha ypically occurs in eldery women wih a history of Hashimoto thyoidits The clinical presentaon is a symptomatc rapidly enlarging goter with a very firm texture. Patiens may also have systemic lym phoma symptoms and atea cervical ymphaden opathy. The diagnosis can be made by FNA. Treatmen ypicaly involves chemotherapy and/o radiation herapy Sug ery generally is not indicated but can be used to aid n diagnos when NA is no inmative.
the trend there s evidence that arger tumors are ncreasingly being discoveed. The vast majoriy of patients wih thyrod cancer have weldierentiated thyoid cance with excelent long-erm surviva The maor rms and her elative requency ae listed in Fg 10. The most common ell-dierentiated thy roid cances are papilary papilary-llicular variant and llcuar. There are rare, ess well-dierentiated varans of papilay thyroid cancer (coumnar tall cell insular oxyphilic cear cell diuse scerosing) that are more aggressive and carry a worse prognosis. Anapastic thyroid cancer is undi ferentated and is the most aggressive rm of thyroid cance 1year surviva aes range om 20% o 30%. Staging and prognosis of weldiferentiated thyroid can cers papillary and licular) ae based on the American ont Commitee on Cancer crieria which include age <45 o 45 years), primary tumor sie local and distan metastases and capsuar and Jymphovascular nvasion. owever because he maority of patients have excelent suvival T (tumo) N (node) metastasis) staging pays a minimal role in the management of thyroid cancers Instead decisions egarding teament are aimed at lowering the lielihood of recurent dsease Treamen of wel-diferentiaed hyroid cancer includes a combnation of surger, radoactive iodne, and levothyrox ine suppresson. The extent of sugey is lagey based on the tumor size soitay tumors smaler than 1 cm may be suffi cenly managed wih lobectomy alone Paens ih larger tumors multical disease, noda metastases or a hitory of irradiation are best teated with toal or near-total thyoidec omy. or patients younger han 45 years o age with a tumor smaler than 4 cm and no evidence of nodal or distant metas tases hemithyoidectomy may be a reasonable alternatve to tota thyroidectom The decision to administer adioactive iodine s based on two ctors: impovement in motality rates and/o reduction in recurrence risk Paients with dsant metasases have improved survival wih successfu radoodine
Thyroid Cancer The incidence of hyroid cancer is rising at a ser rate than any other type of malignancy the incidence ha more than doubled in the ast 30 year This incease is due solely to pap illay cancers, wh the hghes ae of rse occurrng in tumos measuring less han 2 cm. Meanhile, he surval rate r thyroid cance ha remained table o slighy mpoved Autopsy series reveal hat occu hyroid cancer measuing Jess than 1 cm may be identied in as many as 20% of disected specimens. This nding coupled wih the improving survival rate has Jed some investigators to concude that the change in ncidence o thyrod cancer is due soley o increased inciden ta deection of indoen umo becue of greaer use of imaging modalities. Alhough there is ite doub tha esca laed detecon of otherwise occut umos has contributed to 52
• Papilay • Follcular Med • Anapast Ohr (hyro ymphoma an mastass fom ohr ars)
FIGURE 1 0.
Relative equency of the types o yrod ner.
Data fo Hundahl SA, Fleming ID, Fremgen AM Meck HR. A Natnal ne Daa Base reprt on 53856 ae of tyroi arinoa teate in te U 1985-1995 Cacer 1998 Dec 15;83(12):3848 PMID 987447]
Reproductive Disodes
theapy, whereas administration o radioactive iodine ma decrease the likelihood of recurrent disease in hose patiens with nodal metastases. Suppression oTSH with levohroxine therap ma also be used to improve morbidi and reduce mortali paricular in patients with persistent disease or distant metastases The necessar degree o TSH suppression varies according to the risk o cancer progession and comor bidities o the patient Patients with persisten disease tpi call require lowering o theirTSH level to less than 01 µU/mL (01 mU/L), whereas those who are ee o disease but have a high risk r recurrence should have a targetTSH level oO. to 05 µU/mL (01-05 mU/L) r 5 to 10 ears Those patients who are disease-ee with a ow risk o recurrence should maintain aTSH level o03 to 20 µU/mL (0.3-20 mU/L) Medullar throid cancer represents less than 0% o all throid cancers Approximatel 25% o medullar throid can cers are hereditar; all patients with medular throid cancer should be screened with proto-oncogene sequencing Medulla throid cancer ma be associated with several sn dromes including multiple endocrine neoplasia pe 2A (MEN2A) (which ma nclude pheochromoctoma and hper parathroidism) MEN2B (marnoid habitus and mucosa! ganglioneuromas) or milia medullar throid cancer (med ular thoid cancer alone) Biochemical screening r pheo chromoctoma with measurement o plasma ractionated metanephrine levels should be done in all patients with an mutation prior to throidectom • The vast majorit o patients wit well-dierentiated throid cancer have excelent long-term suvival. • Treatment o welldierentiated throid cancer includes a combination o surgery adioactive iodine, and levo thoxine suppression o throid-stimulating hormone r patients with persistent disease or high risk o recurrence RET
ET
KEY POINTS
Reproducive Disorders Physiology of Female Reproducion
A regular, predictable menstrual ccle requires coordination o inhibition and stimuation beween the hpothalamus (secreting gonadotropin-reeasng hormone [GnRH]) the pituitar (secreting llicle-stimulating hormone [FSH] and luteinizing hormone [LH), and the ovaries (secreting estra diol and poson) Th coodnaion o thse sinals is reerred to as the hpothalamic-pituitar-ovarian axis The GnRH pulse equenc varies throughout the menstrua ccle to promote llicuar development and ovulation The phases o the menstrual cce are reerred to in reerence to the activit o the ovar (llicuar and uteal phases) (Figure 11).
8�
�
8
� Theca cells
9 , --- > Granulosa cells
8
Ovulation I Androstenedione Esadiol . Fml pi xi Pl f RH L SH p· i H l i g (piiply i) pi i biz l i g l S g l l l p ib B bk g S p FS = llig ; RH gpg m; = iig il)= gi bk FIGURE 11
FSH under control o pulsatile GnRH secretion, rises in the earl menstrual ccle to promote recuitment and gowh o a llice containing a microscopic oocte (llicuar phase). Granulosa cells ng the ll cle secrete estradiol wich contrib utes to negatve eedback inhibition ofFSH secretion and result ant monollicular development n the majorit o women. Estradiol aso stimulates endometrial proieation Futher into the lcular phase estradiol levels peak and exert acute positive eedback on the pituitar gland wch elicis an LH surge.Ts LH surge results in ovuation and initiates the lutel phase o the menstrual cce. LH stimulates androgen productionb the theca cells wch also line the licle; androgen is subsequentl aro matzd to estrogen in the granulosa cells via aromatase eme. Aer the LH surge and olation, the llicle develops nto the corpus lute wich secretes both estdiol and pogesterone and causes the secreto phase o the endometri in prepara tion r plantation o a ertlzed oocte With implantation the earl emro produces human chorionic gonadotropn, wch mantans the copus lute However, when a eed embro is not present, progesterone leves decline, leadng to the men strual phase o the endometriu and menstul bleeding An average menstrual ccle ranges om 25 to 35 das engh. The llicular phase ma var in each woman but is tpical om 14 to 21 das Variabiit in a menstrual ccle is tpicall the result o a shortened or lengthened licular phase, more comonl seen during the rst 5 ears o menstration A decrease in llicular phase length occurs common in peri menopauseThe luteal phase is usual 4 das and is constant. Inthanwomen ccles less 25 dasounger or greatethanthan40 35earsdasoaeage,likelmenstrual anovulato KEY PON
• n women ounger than 40 ears o age, menstrual cces less than 25 das or greater than 35 das are ikel anovator 53
Reproductive Dsordes -
-
Amenorrhea Clinial Features Pmy Amoh Primary amenorrhea is the absence of menses by age 16 years accompanied by normal sexual hair patern and normal breast development Primary amenorrhea with absence of thelarche (breast development at the beginnng of pubery) and/or adrenarche (androgen producton increase ha typically occurs a age 8 or 9 years) prior to 14 years of age should be evaluated. Pregnancy must be ruled out in any paient wih primary amenorrhea bere additional evaluaion occurs Causes of primary amenorrhea may be genetic, hormonal or structural Fifty percent of patients with prmary amenorrhea have a chromosomal abnormalty such as Turner syndrome (45XO) (gonadal dysgeness) athough some patients with Turner mosaicsm may have secondary amenorrhea (see Secondary Amenorrhea) urner syndrome is commonly characterized by oher cinical manifestations such as shor stature neck webbing recurrent otis media with hearing loss, aoric coarctaton and bicuspid aortic valve The diagnosis of Turner syndrome may be made wth a karyotype Approximately 15% of patents presenting with primary amenorrhea may have an anatomic abnormality of the uterus cervix or vagina such as mllerian agenesis transverse vagina sepum or imperrate hymen Digital vaginal examination transvaginal ultrasound or MRI my help to denti outfow tract anomalies. KEY POINT
• iy percen of patiens with prima amenorrhea have a chromosomal abnormality such as Turner syndrome (45XO (gonadal dysgenesis); 15% of patients presenting wth primary amenorrhea may have an anaomic abnormaliy of the uterus cervix or vagina
Scody Amoh Secondary amenorrhea is the absence of a menstr ual cycle r three cycles or 6 monhs in previousy menstruating women The most common cause of secondary amenorrhea is pregnancy A potential structural cause of secondary amenorrhea such as Asherman syndrome should be con sidered Asherman syndrome is an uncommon complica tion of dlation and curetage intrauterine device place m u u uh hyr myomectomy i is caused by ack of basal endometrum proliferation and frmation of adhesions (synechiae) Diagnosis should be considered in any woman wth amen orrhea and past exposure to uterine instrumentation The classic presentation is amenorrhea or scant bleeding during perods (hypomenorrhea) with ovulatory symptoms (cervi cal mucous changes adnexa tenderness associaed wth fllicle frmation) or premenstrual symptoms (mood changes or breast tenderness) Some patents will maintain 54
small functional pockets of active endometrium with out low obstruction by synechia closer to the cervix resultng in cyclic pain and hemaometrium identiable on ultra sound. Aer structural causes and preg nancy are excluded the hormonal status should be assessed Low estradiol and inap propriately normal FSH and LH levels indicate hypogonado tropic hypogonadism and point to a central cause (hypothalamic-pituitary) Low estradol n he seting of elevated FSH and LH levels indicates hypergonadotropic hypogonadism and ponts to ovarian insufciency The most common hormonal cause of secondary amen orrhea is polycystic ovary syndrome (PCOS) (see Hirsutism and Polycystic Ovary Syndrome) which accounts r 40% of cases. Additional hormonal causes of secondary amenorrhea nclude hypothalamic amenorrhea (hypogonadotropic hypog onadism) hyerproactinemia thyroid disease and prema ture ovarian insuficiency (POI) (hypergonadotropic hypogonadism) Hypogonadotropic hypogonadism caused by hypotha lamic amenorrhea (HA) or nctional hypothalamic amenor rhea (HA) aecs 3 % of women between the ages of 18 and 40 years. Ris ctors include low BM! and lo w body t per centage rapid and substantial weight loss or weight gain eaing disorders excessive exercse severe emotional stress or acute and chronic illness SH and LH levels are inappro priately low in HA but may be inapproprately normal in FHA Estradiol levels are typically o and patients may experience vasomotor symptoms and sleep disturbance If left untreated patients are at ncreased risk r osteoporosis owing to ths lowestrogen state Recovery of menses may occur f BM returns to normal Cognitivebehavoral therapy r cases caused by emotional stress has been shown to be efectve Hyperprolactinemia causes secondary amenorrhea through direct inhibition of GnRH secretion Treatment of the cause of hyperprolactinemi typically results in restoration of menses Hypothyroidsm may cause secondary amenorrhea through increased thyrotropinreleasing hormone levels which causes stimulation of prolacin secretion Hypergonadotropic hypogonadsm as a result of POI is defned as amenorrhea bere age 40 years in the setting of two elevated SH levels (>40 mU/mL [40 U/L]) more than 1 month apart Possibe causes include Tuer mosaicism (in which secondary amenorrhea may occur due to PO) agile X mun hmhy an ummu oophoritis In patents in whom an autoimmune cause is diag nosed evaluation of other endocrine organs (thyroid parathy roid pancreas and adrenal) is recommended at the time of diagnoss and annually thereaer Estrogen replacement s necessary in patients with hyper gonadotropic hypogonadism to prevent bone mass loss until the average age of natural menopause (50-5 years) Esogen replacement preparations are available in oral transdermal subcutneous and vagnal routes of administraton The dose
Reproductive Disorders
of estrogen required by young women is titrated to prevent vasomotor symptoms and vaginal dry ness and may be higher than that used in an older age group. Because spontaneous ovulation may occur (although it is inrequent), counseling on contaceptive options should also be provided r sexually active women not desiring pegnancy Cycic progesterone exposure should be consideed in patients with an intact uteus to prevent excessive unopposed endometrial prolifera tion Oocyte donation may be considered r feiliy options r this paien population KEY POINT
• The mos common causes of secondary amenorhea are pregnanc srucural abnormalities and polycystic ovay syndome.
KEY PONS
• Aer excluding pregnanc, the laboatoy evaluation of primary and secondary amenorrhea includes measue ments of prolactin, lliclestimulating hormone lute inizing hormone, estradiol, and thyroidstimulaing hormone • f homonal evaluaion r amenorrhea is negative the nex sep is a progesterone challenge test; if the paien bleeds wihin 1 week of completing 7 to 0 days of po gesterone, estogen deciency is no the cause and PCOS should be considered
Hyperandrogenism Syndromes Hrsutsm and Polycystic Ovary Syndrome
Evaluation of Amenorrhea A thorough history and physical examination including a pelvic examination, are needed o evaluae both primary (no hisoy of menstruaion and seconday amenorrhea (cessation of menstruation afer menarche. Urine or serum human chorionic gonadotropin (HCG) testing should be done rst o exclu de pregnancy as this is the most common cause of amenorrhea In patients with primary amenor rhea a karyotype is recommended if a pregnancy test is negative Serum levels of prolactin FSH, LH estradio and thyroid-stimulating hormone (SH) shoud then be obtained in the evaluation of primar y and secondary amen orrhea Abnormal levels of polactin and/or SH suppor a nonovarian cause of amenorhea Elevations of FSH and H levels in the presence of a low estradiol level support the diagnosis of PO I If no elevations in these hormones ar e und a pogester one challenge tes (oral medroxyprogesterone acetate 10 mg r 710 days) may be used to determine if the amenorrhea is due to estrogen decienc If the patient has menstual bleed ing within 1 week of completing 7 to 10 days of medroxypro gesterone estrogen deciency is not the cause. In this case PCOS (or a similar diagnosis should be considered If no menstual bleeding occurs, the patient has a low-estogen state and hypogonadotopic hypogonadism is the diagnosis (see Disorders of the Pituitary Gland Pelvic ultrasound is helpful to identify structural causes of amenorrhea such as mllerian agenesis and intrauterine synechiae Salineinusion sonohysterogram can identify intrauterine synechiae, and transvaginal o transabdomina ultr asound can identify absence of a uterus in patients with mllerian agenesis Endocrinology consul fndings suspicious r a genetic cause of amenorrhea may be appropriate A pituitary MRI may be ind icate d to exclude other intracranial causes of hypogonadotropic hypog onadism when diagnosing HA or FHA, and consulation with an end ocrin ologist is recom mended befre imaging is pursued
When hirsutism is present, the patient should be assessed r virilization or development of male characterisics. Rapid onset and progression of deepening of the voice severe acne clioromegal and male patern balding are signs of viriliza tion and are concerning r an ovarian or adrenal tumor. Age of onset aer 30 years is also a risk ctor r an androgen secreting tumor In patients wih hirsutism or viilzation recommended initial laboratoy tests include measurement of plasma dehy droepiandrosterone sulate (DHEAS level and serum levels of SH prolactin total testosterone, and llicular-phase 17hydroxypogesteone. Normal leves exclude adrenal umors hypothyroidism hyperprolactinemia and ovarian tumor Common rms of ate-onse congenia adrena hpepasia oen mistaken r PCOS, can be excluded with a normal 17hydoxyprogesterone level Pelvic ultrasound and adenal C should be perrmed to exclude an ovarian or adrenal neoplasm i the seum total testosterone level is greate than 200 ng/d (69 nmol/}. Adrenal C is necessary to exclude an adrena coisol-secreting and/or androgensecreting neoplasm if the plasma DHEAS level is greater than 700 µg/mL (189 µmol/) Hirsutism is typically a benign condition most commonly om PCOS A marked elevation of tota testosteone or DHEAS is not compatible wth a diagnosis of COS PCOS has a prevalence of 7% to 0% and is one of the most common endocrine disorders in young women. wo sets of diagnostic criteria are commonly used he 2003 Amercan Society r Reproductive Medicine and the European Society of Human Reproduction criteia r PCS require wo of the l lowing three ndings in the absence of other endocine disor ders: (1) oligoovulation or anovulation (2 clinical or biochemical evidence of hypeandrogenism (such as hisutism pholo in at least one ova he 990 cieia om the National Instiutes of Heath and the Nationa nstiue of Child Healh and Human Development require all of the owg r diag nosis of PCOS: oligoovulation, signs of androgen excess (clini cal or biochemcal) exclusion of other disorders that can esul in menstrua iregulari and hyperandrogenism 55
Reproductive Dsodes
A constant stagnant llicular stage is seen in PCOS, resulting in unopposed estradiol secretion om small ovarian llicles. Owing to disordered secretion of LH by the anterior pituitar intraovarian androgen production is also increased in PCOS, resulting in the hyperandrogenism associated with the disorder Women with PCOS typicaly have elevated rest ing LH levels In patients trying to conceive his can lead to lse-positive indication of the ovulatoy H surge on home urnary H kis r ovulaion Estradiol secretion results in proliferation of the endome trium in the absence of progesterone secretion om a corpus luteum. Ths predisposes patients to endometrial hyperplasia and heavy menstual bleeding as a result of anovula ory bleed ing Oigoovulation and anovuation result in infertility but are ypicaly correctable with clomiphene cirate or letrozole r ovlation induction if fertility is desired f fertility is not desired oral contracepives should be considered if not con traindicated Addition of oral contraceptives wil increase secretion of sex hormonebinding globulin (SHBG) and decrease circulating levels of ee testosterone !f a paient has a contraindication to oral conraceptives a progestin-secreting intrauterine device or cyclic oral or vaginal progesterone should be given to prevent prolonged unopposed esrogen exposure. Hyperandrogenism may present as hirsutism acne or androgenic alopecia n paients wih hirsutism desiring treatment existing termina hairs wil need to be removed with depilatory methods, but the rate of hair growh whie on treatment will decrease. Spironolactone an aldosterone and androgen inhibitor may be added after 6 months if acne and hirsutism are still cosmetically bothersome. Bere initiation of therapy the patient should be counseled about teratogenic eects on a male feus and conracepive counseling shoud be provided Both obese and lean women with PCOS also have insulin resstance and studies have identifed an increased incidence of metabolic syndrome obesi impaired glucose tolerance and ype 2 diabetes mellitus in these women Although insulin resistance may improve with weight loss the use of insulin sensitizing agents such as metrmin is associated with a decrease in serum androgens; however it is not very efective as a single agent r ov ulation induction. valuation of paients with PCOS shoud include assess ment r signs of sleep apnea hypercholesterolemia and ty liver. n women with a thickened endometrium or menome trorrhagia endometrial sampling with endometrial biopsy Weight loss and exercise should be emphasized KEY POINTS
• Polycysc ovary syndrome has a prevalence of 7% to 1% and is one of he mos common endocrine disor ders in young women t is oen assocated with insuin resistance meaboic syndome obesiy and pe dia etes mellitus (Continued)
56
KEY PO N S
(conti nued )
• Polycystic ovary syndrome can be diagnosed if wo of the llowing hree ndings are present: 1) oligo-ovua tion or anovuaton ) clinical or biochemical evidence of hyperandrogenism such as hirsutism or acne or (3 ultrasound fndings of polycysic ovarian morpholo in at least one ovar • The 1990 criteria om the National Institues of Heath and the National nsttute of Child Health and uman Development require al of the llowing r dagnosis of PCOS oligo-ovuation signs of androgen excess (clinical or biochemical) exclusion of other dsorders hat can resul in menstrual irregularit and hyperan drogenism
Androgen Abuse in Women Anabolic steroids may be abused by some women to enhance their athletic perrmance or physique. Such exogenous administration may resut in absence of GnRH pulsatility and resultant hypogonadoropic hypogonadism and amenorrhea Adverse eects may include hirsutism acne, deepening of the voice decreased breast size and clitoromegaly Withdrawal of exogenous androgens does no result in severe hypogonadism as it does in men and most women return o regular men strual cycles
Female Inferiit nfertility is defned as the absence of conception aer 1 year of unprotected intercourse on average twice weekly in a woman younger han 35 years of age nvestigation shoud begin after 6 months if no conception has occurred in a woman 35 years of age or older nferiliy evaluation should include a carel medica history of both pa rtners with specia cus on menstrual history previous exposure to sexuay transmitted infections pevic surgery and previous obstetric complicaions such as miscarriage or cesarean delivery. f a repor of oligomenorrhea is elicited, measurement of serum SH and prolactin evels is appropriate to exclude hyroid dis ease and hyperproactinemia as causes of oligo-ovulation Further evauation of inferiliy causes ypically includes semen analysis of the male partner, conrmation of ovulation with measurement of midlutea progesterone level (>3 ng/m [9.5 nmol]), and because alopian tubes may be obstructed patency evaluaion with hysterosapingogram. A common cause of tuba l occlusion and resultant infertiiy is past pelvic inflammaory disease aparoscopy r evaluation of pelvic adhesions or mild endometriosis may be warranted in patients with dysmenorrhea, previous exposure to sexually transmit ted inctions, or previous pelvic surgey. f no abnormalities are und treament to enhance endogenous gonadotropin release and increase he numbers o oocytes ovulated monthy may be warranted. Some studies
Reproductive Disodes
support moving directly to n vitro fertilization treatment r women wth infertility at age 40 years. In women treated wth ovarian stimulation, ora medications such as clomi phene citrate or etrozole are typically used. This therapy is not appropriate in patents with POI Patients should be counseled about the 5% to 8% risk of multipe gestation with these therapies. Referra to a reproductive endocrnologist is recommended.
eydg cell production of testosterone occurs in a diurnal pattern with the highest concentration obseved in the morn ing. A arge percentage of circuating testosterone s bound either to SHBG or albumin A seum total testosterone level measured in the early morning is generally considered to be an accurate measurement of a patient's androgen status but it does not account r decreased SHBG as seen in obesiy (see Evaluation of Male Hypogonadism
KEY POINT
• Inertiy evaluation in women should include a med ca history o both partners with special cus on menstrual histor previous exposur e to sexually transmtted infections pe vc surgery and previous obstetric complications such as miscarriage or cesar ean delivery
Physiology of Male Reproducion Contro of spermatogenesis and testosterone production depends on the pulsatile secretion of GnRH om the hypo thalamus as well as subsequent downstream stmulation of the anterior pituitary and male gonads. In the testicle, FSH stimulates Sertoli cell spermatogenesis and LH stimulates eydig cell testosterone production Negatve feedback om testosterone production inhibits FSH and H secretion at the level o the anterior pituitary as wel as pulsatile hypothalamic GnRH secretion. Inhibin B produced by the Sertoli cells also inhibits FSH (g 12).
G Leydig cels
9 Seol cells
Testoseone
Spermatogenesis I
8
nhbi B
Estadio Dydotestosteroe 1 2. Male epodctive axis Pulses of GnRH ect plses of LH ad FSH FSH acts o Sertoli cells, which assist sem matatio ad rodce ihibi B, the majo egatve relator of basa FSH prodc tio The eydig cels rodce testosteone, whch eeds back to ihbit GRH ad H elease Some testosteone s reversibly coveed to dhydotestosteone o estrad ol, which are both moe otet tha testosteroe i sressg GnH and H SH = foicle-stimuat homoe; G gonadotoi-eleasig hormoe; H = teiizig hormoe (ccled) eatve eedback FIGURE
Primay Hypogonadism Prmary hypogonadism or testcular ilure represents a decrease n testosterone or sperm production. P rimary hypo gonadism is uncommon and may have congenita or acquired causes Klinefelter syndrome is the most common cause of congenital primary hypogonadism Klinefeter syndrome is a common cause of hypergonadotopic hypogonadism and azo ospermia resulting in inrtly A 47X karyoype is diag nostic of Kinefelter syndrome. Mosaic variants of this cond tion exist but typcally present with oligoasthenospermia testicular lure or hypogonadism Concomitant symptoms often include sexual dysunction and generalized tigue al stature is a common finding. Patents with Kineelter syn drome may il to achieve puberty or may present aer sexual maturation with azoospermia. xposure to chemotherapy or radiation may also result in primay testicular iure oca injuy as a result of torsion orchits or trauma may result in ischemia and necross of testicular tssues
Secondary Hypogonadism
GnRH
8
Hypogonadism
ypically secondary hypogonadism is a result of nsufcient GnRH production by the hypothalamus or decent H/FSH secretion by the anterior pituita. Causes may be congenital or acquired. Idiopathic hypogonadotropic hypogonadsm with anosmia (Kallmann syndome) or without anosmia is the most common cause of congental seconday hypog onadism Acquired secondary hypogonadism is most com monly iatogenic due to exogenous testosterone adminsta tion Untreated sleep apnea and obesity are other common causes ther acquired causes include hyperprolactinemia chronic opioid use glucocorticoid use or intrative disease (lymphoma or hemochromatosis).
Andogen Deficiency in the Aging Male The natural progression of mae aging involves testosterone level decline Most men will not become hypogonada and the decine in testosteone poduction is highly variabe with each person. "ow has become a part of the popuar vernacuar owng to aggressive direct-toconsumer mareting and describes many symptoms that may or ma y not be associated with a low seum testosterone level in men. Both prescription and over-the-counter testosterone and dervative sales have surged in the nited States and many other countries With 57
Reproductive Disordes
the increased sales of testosterone rmulations to treat aging men, questions have emerged about the potential adverse eects of exogenous testosterone theapy, particulary in men who have no biochemica evidence of testosterone deciency. Potential adverse eects include increased risk of cardiovascu lar disease and death venous thromboembolism, and prostate cancer.
hypogonadotopic state is revealed, transferrin saturation and ferritin levels should be evauated to exclude hemochromato sis. MRI of the pituitary should be perormed to evaluate r hypothalamic or pituitay masses as the cause of the hypogon adotopic state if no conunding medications or reversible secondary causes are discovered Fige 13 shows an algorithm r evaluating male hypogonadism. KEY POINTS
Evaluation of Male Hypogonadsm A thorough history and physical examination are essential in the evaluation of hypogonadism. A seep history is especially helpul. A large constellation of nonspecic symptoms is asso ciated with male hypogonadism, which makes diagnosis and treatment based on symptoms alone not advisable. Nonspecifc symptoms include ftigue, decreased muscle strength deceased libido, amotivational state, or decreased robustness or equency of erections Testosterone measurements are not recommended if ony nonspecic symptoms are present; rather investigation of other causes of the patient's symptoms is appropiate More specic symptoms include necomastia, diminished testicular volumes and absence of morning erec tions. Measurement of testosterone leves is not ecommended if a patient is having egular morning erections does not have true necomastia on examination and has a normal testicu la examination as it is highly unlikely that he has testoster one defciency Testosterone deficiency is diagnosed with two early morning serum total testosterone levels below the refer ence range. Because illness and strenuous activity can alsely lower testosteone levels, measurement should occur in healthy men who have avoided strenuous activity fr several days. Measurements of the testosterone level occurring ater in the morning or in the aftenoon are not useful r interpretation Consultation with an endocri noogist should be considered if two ealy morning total testosterone leves are low. In certain cinical scenarios such as morbid obesity total testosterone may be low but free testosterone may be normal. Free testosterone assays can be unreiabe, and routine measurement of free test os terone is not recommended Free testosterone by equilib rium dialysis is the gold-standard assay. Once conrmed, the cause of hypogonadism (primary or seconday) shoud be further investigated prio to initiation of testosterone replacement. Serum LH FSH proactin, and TSH levels shoud be measured. Primary testosterone defciency (hypergonadotopic hypogonadism) is diagnosed when SH and LH levels are anky elevated in the presence of a simul taneously low testosterone level Low or inappropriately nor mal FSH and LH levels in the presence of simultaneous low testosterone evels ae diagnostic of secondary hypogonadism (hypogonadotropic hypogonadism. A hypergonadotopic state (elevated LH and FSH eves) should be rther investigated with a kayotype if no history of gonadotoxic theapy or testicular insult is eicited. If a 58
• Measurement of testosteone levels is no t recommended f a patent is havng regular mornng erectons does not have true necomastia on examination and has a normal testicular examinaton as it is highly unlikely that he has testosterone deciency • Testosterone deciency is diagnosed with two early morning total testosterone eves below t he referene range. • Once testosterone deciency is conrmed the cause should be rther investigated prior to initiation of tes tosterone replacement
Testosterone Replacement Therapy Testosterone replacement therap y is a widely used treatment r men with hypogonadism Possibe beneits seen with testosterone replacement therapy, such as improved libido energy evel, and bone density have been described but remain controversial Testosterone therapy has been associ ated with increased hemoglobin and hematocrit levels, worsened obstucti ve seep apnea, and a d ecrease in HDL cholesteol levels. LDL cholesteol levels do not appear to be afected. Although hypogonadism remains an independent risk ctor r motalit recent studies have examined the as so ciati on between testosterone therapy and cardiovascular risk The association between testosterone therapy and mortaity has remained contoversial. Physicians prescribing testoste rone therapy to elderly men with biochemically proven testosteone defciency and comorbidities shoud use it pu dently with close llowup. Cardiovascular disease isk as well as risk r thrombosis should be discussed with patients bere pursuing theap Prescribing testosterone therapy in the absence of biochemically proven testosterone deciency puts the patient at isk r iatroenic hperadoe im wih subsequent increased risk of myocardial inrction stroke death, venous thromboemboism polycythemia and obstructive sleep apnea. Pescribing testosterone theapy in the absence of a full evaluation may delay treatment r sec onday causes such as prolactinoma, hemochromatosis, or intracranial mass. Although implantable pelets and injectable testosterone preparations are available, the most popular testosterone prep arations cuently are topical (most commonly hydroalcoholic
V
Reproductive Disorders
Suspec hypogonadism
Measre: total sem testosteoe level (x2)
Normal testosterone
Low testosteoe
Bioavailable/fee testosteroe ad/or SHBG i appoprate patients
ollow
Cofimed ow testosteoe Check FS and levels
igh SH or H level
ow or normal FS or level
Pimay hypogonadism
Secoday hypogonadism Chec PR leve, io tdies
Elevated PR level other pititary defciecies Sigs/symptoms of mass effec, testosteroe level <150 g/d (5.2 mol/)
levated tansfe satatio, feriti level
Pititary MRI
emochromatosis
Algorithm fo evauatng le hypogonadsm. FSH folce-statig hormoe; L H = lenizig horone; PR roacti SHBG sex ormoebidng gol 2 wo seaae measureents. FIGURE 13.
gels). They require daily use and may incur signicant cost to the patent, bu the steady level of testosterone achieved within 30 minutes of application is an appealing eature Inadvertent absorption by patient contacts may occur; users should be inrmed that vir ilization of contacts is not uncom mon and premature puberty can occur in exposed children. The patient should aso be counseled that decline in endog enous testosterone production and spermatogenesis may occur. f fertity is desired testosterone therapy shoud be avoided and consultation with a reproductive endocrinolo gist is recommended Patients requirng testosterone replacement therapy should hae testosterone levels monitored at 3 and 6 mons aer initiation and annually theeaer the goal toal tesoste-
rone leve should be in he mid-normal range. Monitoring of the prostate specifc antigen and hematocrit level should llow Endocrine Society gudelines (Table 29). KEY PONTS
• Testosterone defciency should be diagnosed bochemi call and its cause shoud be defnitively determned bere nitiation of testosterone repacement therap Patients requiring testosterone replacement therpy should have testosterone prostate specic antigen and hematocrit levels monitored. • Goal total testosterone level shoud be n the mid normal range r patients requiring testosterone therap
59
Reproductive Disodes
TABLE 29. ndne Sey C nal Gdelnes f Mn ng Adese es f essene elaemen heay Paaete
eended eenng ede
Aes
Hematocri
Value obained at baselne and hen a 3 monhs and 6 monhs aer herapy iniaton, oowed by yeay measrements
Vae>54%
PSA level
For aens>40 yeas of age wt a basene vae>0.6 g/m (0.6 µg/L) DRE and SA leve (deermed at ad 6 mots aer teay iitation olowed by rega screeing)
Increase>14 ng/m ( 1.4 g/) n year or>04 ng/m (04 g/) aer 6 mots o se; abomal rests on DR AUA rostae symoms scoe/ ISS >19
AUA = American ologcal Asscation; DRE = digtal ecta l exainatn; IPSS = Intenatonal Postate Symptm Sce PSA = postate-specfc atge. ata fom Bhas S, Cunngam GR Hayes FJ et al Testosteone teapy men wt adge defcency sydomes: an Edoce Socety Clca l Pactce Guideline. Clin Endocrinol Mtab 2010;95(6):2550 IPMD 20525905]
Anabolic Steroid Abuse in Men Testicular testosterone production is suppressed in the pres ence of exogenous testosterone administration. Many elite athletes abuse androgens in injectable r m, and herbal prep arations of oral testosterone are eadily available. Commonly used androgens include injectable testosterone esters and ora alkylated testosterone peparations. HCG inections mimic LH stimulation to the Leydig cells and result in ele vated testosterone levels Although ths therapy is appropri ate in men with hypogonadotropic hypogonadism, it may also be abused. Aromatase inhibitors are equently used concurrently with exogenous testosterone preparations to prevent adipose conversion of estrogens to androgens and development of gynecomastia. Androstenedione supple ments are commonly abused Excessive musce bulk acne, necomastia, and decreased testicular volume may be und on physical examnation in patients using anabolic steroids. Ireversible hypogonadism may result and oen presents as male ineility with oligosperma or azoospemia on sperm analysis Permanent inabiliy to produce endogenous estosterone may occu. Extatesticular eects may also be noted including low HD choesterol level hepatotoxc i eryocytosis, and increased risk of obstructive sleep apnea. Mood disoders are common i anabolic steroid users. Labotory sudies showing low or nomal gonadotropi levels and a low testosterone level with cinical evidence of hyper andogenism are consistent with use of a non-testosterone containing product, such s one containing androstenedione, or cessation of longstanding (ypically greater than 1 year) anabolic steroid use with ilure to recover endogenous tes tosterone function. 60
KY OIN
• xcessive muscle bulk acne necomastia and decreased testicuar voume may be seen on physcal examination in male patients using anabolic steoids • xogenous testosterone use may resul n irreversible decline n spermatogeness and resutant inferli, as well as pemanent inabily o poduce endogenous tes tosterone
Male Infeility Physica examination should include assessment r the pres ence or absence of the vas deferens evaluation r congenial bilateral absence of the vas deferens (as seen in cystic ibrosis), assessment of testicular volume, and evaluation r the pres ence of hea varicocele, or tumor Semen analysis obtained aer 48 o 72 hours of abstinence om sexual activiy is the best test to assess male fertilit For accurate results, analysis of the sampe should occur within hour of ejaculation Extended abstinence perods ma diminish ructose in the ejaculate and aicialy lower sperm motiliy If the physical examination is abnormal, evaluation by a urologist may be appropriate If semen analysis results ae abnormal the test should be repeated, and referral, f abnormal to a reproductive endocri nologist is warranted. KY ON
• Semen analysis obained aer 48 o 2 hors of abst nence om sexual activy is the bes test to assess male feiity; if abnormal the test shoud be repeaed r conmaton.
Gynecomastia Gynecomastia is glandula breast tissue enlargement in men due to imbalance in the levels or activity of testosterone and estrogen. This imbalance results in an increased estrogento testosterone atio which in turn results in decreased nhibi tory action of testosterone on the breas tissue. The less testos terone and/or more esrogen the breast tissue is exposed to, the more lkely necomastia wil deveop. Athough abnor mal in the pospuberal man it is usually benign. It is typically bilateral but not always symmetric. Unlatera necomasta is uncommon and should be evaluated with mammogram as soon as possible owing to risk of breast cance here are many causes of necomastia ranging fom druginduced (marijuana, alcohol, reductase inhibitors, H2eceptor antagonists, spionolactone, digoxin, ketocona zole, calcium channe blockers, ACE inhibitors, antiretroviral agents tricyclic antidepressants selective serotonin reuptake inhibitors) and hypogonadism (primary, seconday) to chonic illness (hepatic cirrhosis, chronic kidney disease) and endo crine disorders (hperproactinemia, acromegal hyperhy roidism Cushing syndrome). Obesity and aging are associated
Calcium and Bone Disordes
with necomastia owing to inceased in ceased aomatase activity in the peiphe. Estogen-seceting tumos (such as Leydig o Sertoli cell tumos o adenal cotical cacinoma) and HCG seceting tumos (such as gem cel tumos and hepatic caci nomas) ae associated with necomastia. A thoough history should be obtained. The beasts should be examined glandula enlagement, whi which ch typi cally extends concentically fom unde the aeolae, and is fim mobile and ubbey. The beasts may be tende if the time couse is acute Pseudonecomastia is subaeola adi pose tissue without glandula polifeation that is assoc ated with obesit Tue necomastia typcally distots the nomally at contou of the male npple, causing it to po tude owing to the mass of glandua tssue beneath it. In pseudonecomastia the nipple is typically still at but so and nondescipt subcutaneous t tissue is pesent in the beast aea Mild chonic asymptomatic necomasta does not wa ant evauation Evaluation of necomastia that is asymmet ic o concening malignancy (boody nipple dschage, had and fxed associated with egional lymphadenopathy), of apid and ecent onset o lage than 2 cm (>5 cm in obese men owing to the known incease in aomatase activity in obesity) should include measuement of total testosteone, H FSH and TSH levels as well as assessment of live and kidney unction If indicated by ndings on histoy and/o physical examination measuement of polactin, estadio and HCG may also be indicated. If the biochemical evaluation demonstates abnomalities, futhe evaluation with testicula ultasound adenal C o pituitay MRI may be indicated; consultation with an endocinologist is ecommended bee imaging is odeed
V
In both cases, ionized calcium should be measued It will usualy be nomal indicating nomal ciculating ee levels of calcium. Thee ae also instances of aticially inceased cal cium levels due to high potein states as in multiple myeloma (elevated monoclonal immunoglobulins) hypealbumine mia, Waldenstm macoglobulinemia and thombocytosis. In these patents, ionized calcium would be nomal with ele vated total seum calcium itamin D is a tsoluble vitamin and body souces incude de novo poduction fom the skin, though ms und in od and though supplementation (Table 30). hee ae wo ms of vitamin D supplementation: vitamin D 2 (egocalcifeol) and vitamin D 3 (cholecalcifeo). Although both ms ae useful in aising vitamin D levels vitamin D3 may be moe benecial because of tighte bonding to vitamin D eceptos, longe shelf life geate potency than vitamin D2, and being identical to the vitamin D that natually occus in humans afte ultaviolet light exposue. Regadless of the method of ingestion vitamin D3 and D 2 ae both inactive ms that must be hydoxylated twice bee becoming active The st occus in the live and conves vitamin D to 25-hydoxyvitamin D [5(H)D] also known as calcidiol The second occu occus s pimaily in the kidney and foms TABLE 30.
'
Sources of itami itam in D ype o Vtamin
Amount o Vitamin
Cod liver o
Choecacfeo
400-1000 U/ teaspoon
Samon wd caught
Choecacifeo
6001000 U/4 oz
KEY POINTS
Samon canned
Choecacfero
300 /4 /4 oz
• Unilateal necomastia in the male patient is conce ing malignancy and waants immediate evaluation with a mammogam.
Mackee caned
Choecacfero
50 /4 oz
Sundried shtake mushrooms
Ergocacifeo
1600 U/4 oz
Egg yo
Ergocacifeo
0 U/yok
Mild chonic asymptomatic gynecomastia i the male patient does not waan waantt evaluation evaluation
Sources Food Sources
Suigh(one minma eyherma dose)
0000 U in bathng sut
Foied Foods
Calcium and Bone Disorders Cacium Homeostasis and Bone Physiology Seum calcium levels ae tightly egulated on a moment-to moment basis by the actions of vitamin D and paathyoid homone (PTH). The amount of calcium that is albumin bound can be aected by hydation and nutitional status. If albumn levels decease total seum calcium levels may appea low (pseudohpocalceia). Convesel, if albumin levels incease, total caciu levels levels will appea elevated (pseudohpecacea). (pseudohpeca cea).
Mi
Choecacero
Oange jce
Choecacero
Infant fomua
Choecacero
Pharmaceutcal Sources Vitamn D2 Liquid vamn D
rgocacfero
50000 U/capsue
Egocacero
8000 U/capse
uvmn
ocacero and choecacfero
0000 or00 0000 or000 0 U/capsue
Vitami D
Choecacieo
400800 000 000 000 0000 0000 U/capsue
61
Calcium and Bone Disorders
te physiolocly active active ,25-d ,25-dihyroxvit ihyroxvitamin amin D [ ,25(0H)], also known as calcitriol (F 14). Because 25droxvitamin D as a relativel long alf lie o severa weeks, it is te best indicator o wole bod vitamin D status. status. Active vitamin D acts acts on on tree organ sstems sstems to acieve and maintain normal serum calcium: bone, intes tine, and kidne Wit adequate vitamin D, bone resorption is increased, intestinal uptake o dietar calcium is increased, and excretion o cacium troug te kidne is decreased. PTH is secreted to increase te calcium in te bood in response to even te sligtest degree o pocalcemia; it acts on te kidne to increase production o active vitamin D and promote cal cium reabsorption in te distal convoluted convoluted tubule and loop o Hene, and a nd increased resorption in bones, tereb tereb increasing release o calcium into te blood.
Sunlight (UVB)
Cincal Features of Hypecacemia Hpercalcemia is marked b serum calcium leves above te normal range, usuall greater great er tan .5 mg/dL mg/dL (26 mmol/L) Most patients are asmptomatic, and percalcemia ma be notedd incidentall note incidenta ll on laborator tests obtained r oter rea sons. Smptoms ma occur wit an degree o percalce mia but are more likel wen serum calcium leves exceed 2 mg/dL mg/dL (3 mmol!L) Classic smptoms o pouria pouria,, podip sia, and nocturia sometimes occur wit elevated calcium levels o mg/dL (28 mmo!L) or less Oter smptoms suc as anorexia, nausea, abdominal pain, constipation, increased creatinine levels, and mild menta status canges are more likel to occur wit levels greater tan mg/dL (8 mmol/L) As serum cacium levels continue to increase beond 2 mg/ dL (3 mmol/), smptoms become more severe suc as pro und mental status canges, obtundation, acute kidne injur due to pround dedration, and increased creatinine concentration. KEY POINTS
l
k
Hypercalcemia
7-Deydrocoesero Coecacfero vam D3)
ieta Sue f Vitai Coecacero D3 s, mea Erocacfeo Erocacfe o D2 sppemes
percalcea are poluria, pol • Classic smptoms o percalcea dipsia, anorexia nausea, abdominal pain, constipation, and mental status canges as serum cacium levels increase and/or te rate o cange increases, smptoms become more severe, wit pround mental status canges, obtundation, and acute kidne inur. • 25 25 -Hd Hdroxvitamin roxvitamin D as a relative ong alfie o several weeks is te best indicator o wole bod bo d vitamin D staus, and is te recommended test r vitamin vitam in D deicienc Dagnoss and Causes of Hypecalcemia Wen serum calcium elevation is incidentall noted, repeat measurement o serum calcium is indicated and i a second percalcemic level is noted, urer evaluation is warranted to determine te cause ( ). e next step is is determin ing i te te percalcemia is PTH or nonPHmediated b simultaneous measurement o serum calcium and intact PH levels (F ) Ionized calcium ma be used in evauating percalcemia, but it is rarel elpul in diagnosing percal cemia in patients wit normal albumin levels or no acid-ba se disturbances
5ydroxyvam 5ydroxyv am D
15diydroxyvam D3 Matas cacm baace e body
Parathyroid Hormone-Mediated Hpercalcemia Parathyroid Primary Hyperparathyroidis Hyperparathyroidism m Cacm resorpo
Caccao
Bood cacm ad pospors
FIGURE 1 4. Production of vtamin vtamin D PTH = parahyroid homone; VB ltravioet 62
Primar perparatroidism is te most common cause o PHmediated percalcemia, and is diagnosed wit a simul taneousl elevated serum cacium level, wit an inappropri atel normal or elevate elevatedd intact PTH eve e incidence peaks in te sevent decade and aects mostl women (75%). Bere e age o ears, rates are similar in men and women Approximatel 8% o patients will ave elevated PH levels wit simultaneous simultaneous elevated elevated calcium calcium levels Most commonl,
V
Cacium and one Disodes
TABLE 31.
may cilitate management. Seum phosphorus levels are pi cally low or low-normal in these patients. In contrast phos phorus levels will be elevated in atients with vitamin D toxicit. Approximately 50% of patients with primary hype parathyroidism parathyro idism wil have elevated urine calcium levels and the other 50% will have normal levels. Occasionally urine calcium can be low in those patients with concomitant concomitant primary hyper hyper parathyroidism and vitamin D deficienc. Additional patients with vitamin D deciency convert more 25hy 25hydroxyvitamin droxyvitamin D to 125-dihydroxvitamin 125-dihydroxvitamin D so they may have eevated levels of 125-dihydroxyvitamin 125-di hydroxyvitamin D. Parathyroidectomy is the treatmen r primay hyper parathyroidism Surgical management is curative in roughly 90% of patients but evidence that the benet outweighs the risk o the surgical procedure is present under only certain circumstances. here have been several long-term observa tiona studies that und stability in biochemical markers and bone density in patients who do not meet the surgical inter vention criteria listed in . . When one or more of these criteria are met surgery is recommended Surger can be considered when surgical criteria are not met but patients should be cautioned that there are no robust data to support that intervention. t is critical that an experienced surgeon perrm the sur gery to avoid increased risk of postoperative hypoparathy roidism and damage to the recurrent laryngeal nerve. Historically a bilateral neck dissection was done to identi parathyroid gands that appeared to have irregular appearance or increased size. With the increased use of sestamibi scans high-denition ultrasound and intraopeative measurement of PTH evels the minimaly invasive technique is now pre ferred. Minimally invasive surgery allows r a smaller incision and a shortened surgical duration.
Causes of Hypercacemia
Parathyroid Hormone-Mediated Hypercacema P hthd (dn, hl) thd n T hthd Fl h N hthd NoParatyroid-Mediated Hypercalcemia lgnn hl nd ll tt) Vt D txt Vtn A tx Mlk l nd Thx ngd bztn Gnt d (d bl) L Tt ntl nttn
primary hyperparathyroidism is due to a single parathyroid adenoma; however rarely it may be atributed to multigland hypeplasia (tpical in patients with end-stage kidney disease or mutiple endocrine neoplasia syndromes) or parathyroid gland carcinoma (calcium is typically >14 mg/dL [3.5 mmol/L] and intact PTH levels >250 pg/mL [250 ng/] on presentation diagnosis is made histopathologically given the overlap with enign primary hyperparathyroidism) Once diagnosed measurement of serum phosphorus 24hour urine calcium, and serum 25hydroxyvitamin D levels
200
180
160
�
140
Primary yperparatyroidism
120
100
Vitamin D deficiency
80
60
Normal
40
Hypoparahyroidism
20
Hypercalcemia of maignancy
0 6
7
8
9
10
11
2
3
14
15
Seum caciu (mg/d) FIGURE 1
5. Relationship of calcium, PTH and vtam D at i noma oo an in evera eae H = paayroid omone
6
Calcum ad Bone Disorders
TABLE 32. Idctios f Sgc Iteetio i Ptiets with Piy Hypeptyoidis
Increase i serum calcim level �1 mg/dL( 0.2 mmol/) above pper limit oformal• Creainine clearance ms be <60 mUmi (006 Umin T-score (o DEXA sca) of2.5 or wose at he lmba spe, total p, emora eck or dstal radus Age 50 yeas or yonge Suge aso ndcated patets i whom medca seilance is neher desed o possibe icudng tose wh sgicat bone idey, gasroinesta o eomuscula sympoms ypical of prima yperpaatyodsm DEXA = dual-enegy x-ay absorptiomey. 1n otherwise aymptomac patiet.
Recommedaos fom Blezka Kha AA, Pots JT . hd Ieatoal Woksho o he Maagemet of Asymptomat Pmay Hypepaahyodsm Gdeles fo e maageme of asympoma pay hypepaahyodsm: smmay saee fom e d Ieatoal Woksho Cl Edool Metab. 209 Fb;94(2):335-9 IPMD 1919398
. . P x q z . q (40000 PH 30 (7 x 30 7 !. 30 (7 _ q q Parathyoid Carcinoma P M HRPT2 j W 64
q x q 4 (3 M B HRPT2 Tetiay Hypearathyroidism P x P Nomocalcemic Pimay Hypepaathyoidism N P x x 0% 3 Familial Hypocalciuic Hypecalcemia F q (R G CASR " z ( 0 [8 ] P 4 x . H 4 00 4 (0 4 . :
Calcum and Bone Disordes
Ca/Cr clearance ratio= [24-hour urine Ca x seum Cr] � [serum Ca x 24-hour urine Cr A atio less than 0.01 conrms the dag nosis if all oher causes of hpocalciuria (thiazides thium, vitamin D deciency) have been ecluded. FHH is usually a benign condition that requires no interenton but should be ecognied to prevent unnecessay paathyoidectom Other Familial Hypercalcemias Familial hyperparathyroidism is another rare cause of hyper cacemia The disease presentation is almost identical to spo radic primary hyperparathyroidism and a careful miy his tory will suggest the diagnoss. Once a diagnosis o primay hyperparathyroidism is made screening milial causes should be done if the patient (1) is younger han 30 yeas of age at the time of diagnoss (2) has a mily history o hypercalce mia or 3) has a medical history of other endocrnopathies. These paiens should be tested r multiple endocrine neopla sia syndrome types 1 and 2 MEN and MEN2). MEN s chaacteied by nctional pituiay adenoma nctional pancreatic umors and priary hyperpaathyroidsm MEN2A is charactered by medullary troid cancer, pheochro mocyoma and paratyroid gland hperplasia wih the assoc ated RE oncogene mutation. Patients with MEN would llow simiar guidelines r surgical removal of parathroid gands. Medications Causig Hypercalcemia Thiazide diuretics decrease the reabsorption o calcium in the kidney and result in elevated levels Primary hyperparathy roidism however should also be considered if he patient remains hpercalcemic despie the discontinuation of the h aide diuretic In these patients he thiaide may have been masking the PTHmediated hypercalcemia. Lithium decreases the paahyroid gands' sensitivity to calcium and may also reduce urine calcium ecetion Non-Parathyoid HormoneMediated Hecalcemia In contrast to PTH-mediated hypercacemia nonPTH mediated hypercalcemia is associaed with vey low PTH lev els typically less than 10 to 15 pg/dL (1015 ng/L.
Malignancy-Assocaed Hypercalcemia There are wo mechanisms of hypercalcemia of maignancy: local osteolytic and humoal When lyic bone metastases are present percalcemia is the esult of increased mobiliation of cacium om he bone. Humoral hypercalcema is ess com mon and occurs when the tumor sef produces parathyoid related protein (PTHrP) that binds o and activates the paathyroid recepto raising serum calcium evels. Squamous cell carcinomas breast cancers, and renal cell cacinomas are h umos mos commoy assoca w cacma o malignancy In multiple myeloma the hypercalcemia is caused by the release of ctors that stimuat e osteocast activi Oher Causes NonPTH-mediated hypercalcemia can be caused by sev eal other mechanisms Thyrotoicosis can lead to mild
hypecalcemia through increased bone resorpton Resolution of the hyotoicoss should lead to normaliza ion of calcium levels. Prolonged immobiliation and inceased vitamin A evels can lead to inceased bone resopon Increased evels of calcium absorption from the gut can be from makedly high viamin D levels or increased intake of calcium carbonate poducts milk-alkali syn dome) Granulomatous diseases such as sarcoidosis and Wegener ganuomatoss and maignan lymphomas cause hypercacemia though increased --hydroylation aciv ity that inceases 125-dihydroyvitamin D levels and cal cium reabsorption in the gastointestinal tract.
Treatment of Hypercalcemia The teatment of hpercalcemia should cus on decreasing the serum calcium level by ncreasing calcium ecretion and decreasng bone resopton or intestinal cacium absorpion as well as volume repetion. Polyura due to the decreased concen tration abity of the distal tubule is the main cause of dehyda tion in these patients Although many patents do not equire hospitaliation those with marked mental satus changes acute kdney injur, or calcium leves greater than 12 mg/dL (3 mol!L) should be hospialied or treatment. Firstline therapy is aggres sive intravenous uid resusciaton Once the paient is volume replete an ntranous loop diuretic shoud be added if the cal cium level has not normalized. Intavenous bsphosphonate therapy s usually given r longer-term control o hpercalce mia. Caution should be eercised with these agents n the seting of kidney dysncion. Zoledronc acid wile more epensive is a more eecive therapy patients with malignancy-related hpercalcema n patents resisan to or ntolerant of bisphos phonate herap, o -label use of denosumab which also reduces osteoclast-mediated bone resorpton can be used Atention shoud be turned as quickly as possible to treament of the underlying cause of the patient's hypecalcemia to ensue long term maintenance of normocalcemia If the underlyng cause is inceased 125dihroyitamin D hroylation glucocori coids can be eecive therapy but may need to be dosed on a regula basis. For patients who present with seum cacium levels greate than 18 mg/dL (4.5 mmo/L) wth neuroogic symptoms or compomised idney nction hemodialysis is an appropriae choice to quicly reduce calcium levels KEY POINTS
• Primary hyperparathyroidism is the most common cause of parathyroid hormone-mediated ypercalcemia and is diagnosed with simultaneousy elevated serum calcium levels with an inappropriatey normal or ele vated in tact parathyroid hormone leve • Parathyroidectom is cuative in approimately 90% of patients with primary hypeparathyoidism but should be perrmed by an eperenced surgeon using min mally invasive techniques (Continued)
65
Calcium and Bone Disorders
KEY POI NT S
(continued)
• In contast to paratyroid ormone-mediated percal cemia, nonparatyroid ormone-mediated hpercace mia is associated wit very low paratyroid ormone evels, ypically less tan 0 to 15 pg/dL (0-5 ng/L). • Te acute treament of ypercalcemia cuses on decrasng te serum calcium level by increasig cal cium excretion wit vgorous volume replacement, decreasing bone resoption wit bisposponates
Hypocalcemia Clinical Features of Hypocacemia Hypocalcemia, dened by serum calcium levels below te normal range, may be asymptomaic if mild. As calcium levels decrease, particulaly below 80 mg/d (20 mmol!, symp toms may develop, including parestesias (numbness/tingling around e mou, tingling in ngers and toes) muscle cramping (Trousseau and Cvostek signs, decreased muscle sengt electocardiogram canges (prolonged Q/T inteal, tean, and seizures
Diagnosis and Causes of Hypocacemia Asymptomatic ypocalcemia may be noted incidentally on outine laboratory tests. Wen tis occurs, e cacium leve sould be repeated in conjunction wit a serum albumin level. If ypocalcemia is conrmed, simulaneous intact PTH and serum cacium must be measued o conrm if PTH is esponding appropriately Te appropriae pysiologic response to lowe calcium eves is an eevaion in PTH levels
CI I lypopr,1thoids. omonl due u ig eck sugv ( io o podo). s e mos oo as o poa ug d 1 k su gis. he p1toid glnds an ndtl eod o p hid ooe poio e as deese du o dsupion ooo suppl Onl seil masL :m s o lu eels wi i w dag s nse lpopthoids G also be asd b dge ·o a on xpsu. pd gnd i�io. i'it dis ss ootosis Wilson diss. gos o uoimm po atois C
KEY OIN
• Te most common cause ofhpocalceia is ypopar atyroidism wic is most oten due o trauma during surger to te neck.
Teatment of Hypocalcemia Mild, asymptomatic pocacea (sem calcium 80-85 mg/ d [20-2. mmol/]), is a common nding and does not require treament. Calcium carbonate and calcium cirate are te most com mon oal calcium rmulations. Calcium carbonate reuires an acidic environment o be absorbed; terere, all patients wo are on poton pump inibitors sould be prescribed cal cium citrate. Adeuate levels of bot 25ydoxyvitamin D and ,25-diydroxyvitamin D are also essential In te acute pase ofrepletion ,25-diydroxyvitamin D is more eective tan 25-ydroxyvitamin D If te patient is symptomatic or if te ypocalcemia is acute, calcium guconate and calcium citrate are bot available in intravenous m. Goal calcium is 70 to 7.5 mg/d (8-.9 mmol/ wit intravenous repletion, and oral rms can be used once at goal is acieved. Te overall goal ofrepletion is te low to low-normal range (serm calcium 8.0-85 mg/d [2.0-2 mmol/) Ifa patient reuies conic eplacement, usually due to ypoparatyroidism, cae mus be taken t o avoid ypercalciu ria as calcium neprolitiasis and decreased glomelar tra tion rate can occur Cronic replacement typicaly includes calcitriol, calcium and occasionally magnesium. Calcitriol is te vitamin D source of coice because PTH is needed r optimal conversion of25-ydroxyviamin D to ,25diydrox yvitamin D Serum calcium, magnesium, creatinine and urine calcium levels sould be measured at eac llow-up visit Te goal cacium eves sould be low-nomal witou yperca ciuria Te magnesium level sould ideally be greater an 2 mg/d (0.83 mmol!) and creatinine levels soul d remain in te normal ange If te urine calcium level is greater tan 300 mg/24 (hypercalciuria calciumand/or vtamn D repace ment needs to be decreased. Calcium is usually deceased rst te vitamin D levels ae win te normal sciency range KEY ON
• If hpoparatyroidism is te cause ofhocacea cor rection ofany coexisting hpomagnesemia to serum magnesium 2 mg/d (08 mmo!) or ger is necessa
Other Causes Hyocalcemia
Oter less common causes of ypocalcemia include poor calcium intake, acivating mutations in e CASR gene, PTH resistance, increased pospate binding in vascular space (rabdomyolysis or umor lysis syndrome, increased citate celation wit lage volume blood transsions sepsis, vita min D deicienc and ypomagnesemia ow levels of mag nesium (due to alcool abuse or malnutition) activate G-proteins at stimulate calcium-sensing eceptors and decrease PTH secretion 66
Metabolic Bone Disease Osteopenia and Osteoporosis Bone minera density begins to incease wi pubet, and peak bone mass is acieved in early adutood Sex ormones, estro gen and testosterone, are crcial to increasing bone mineral density in women and men respectivel Specicall estrogen as impac on osteocast and oseoblas activity in bot men and
Calcum and Bone Disorders
women Towards the end of pubert, estrogen hats bone resorp tion and signas the cosure of epiphysea plates. Bone mass begins to decine in women aer menopause, with deceased estrogen eves, and in men over age SO years In men, the oss of testosterone typicay acceerates bone oss aer 70 years of age Eary cessation of sex hormone poduction in either sex r any reason, may acceerate the oss of bone minera densit Bone oss occurs when the remova of od bone (osteocastc actiity) exceeds the repacement with new bone (osteobastic aciity). Acceerated bone oss can oen be aributed to hypo gonadism or medications that promote bone oss. Risk Assessment and Screenng Guidelines Decining bone minera density is associated wth ture ac ture risk and therere is an important component of acture risk assessment Indiidua peak bone mass is determined by genetic ctors, nutriton, changes in hormone (estrogen, tes tosterone, troxne) ees, concomitant heath condtions, and physica activity eve. he Nationa Osteopoosis Foundation recommends that a postmenopausa women and men oder than SO years of age be evauaed r osteoporosis.his evauation incudes a thor ough story r potentia risk ctors and physica examination Tis preiminary screening wil determine f bone minea den sity (BMD) or verebra imaging is necessar Table 33 ists sev era common risk ctors r osteoporosis. If a patient is deemed hgh risk a study of BMD with DEXA may hep rther assess acture isk.he DEXA is designed to measure BMD and estab ish risk of acure in postmenopausa women In young men and premenopausa women, assessment of BMD r acure risk is not advised or aidated.able 34 ists the U.S Peventie Sericesask Force recommendations r BMD testng.
TABE 33.
Diagnosis he dagnosis of osteopenia is based on BMD testing Osteoporosis, however can be diagnosed by BMD tesing or cinicay in the patient with history of agiity acture, hip acure, or vertebra compression acure DEXA assesses the densiy of the verebra and hip bones compaed with heathy young-adut sex-matched reference vaues he dista one-third of the radius can be used in patients when the hip or verebra BMD cannot be measured he score is based on the number of standard deviaions above or beow the mean refeence vaue and is known as the score hose patients with scores at -10 and above hae norma bone densi t A score between -1.0 and -2. is dened as ow bone mass (osteopenia) Osteoporosis is dened as a score beow -2 Seere osteoporosis is defned as a Tscore of -2. or beow with one or more actures In women and men younger than SO years, the Internationa Society r Cinica Densitometry recommends that ethnic- or race adjusted Z-scores be usedhe Z-score compares a patien's BMD with others of their same age and ethnicit a nd oseopo rosis/osteopenia cannot be diagnosed in these patients A Z-score of -20 or ower shoud be described as "ow bone minera densiy r chronoogic age or beow the expeced range r age Patients with Z-scores above -20 are within the expected range r age In 2008 the Word Heath Organization (WHO) created the Fracture Risk Assessmentoo (FRAX) cacuator tha ur ther denes the 10-year acture risk r patients with osteope nia, dened as a-score between -10 o -2 on DEXAhe FX score notes the probabiity of major osteoporotic acure and hip acture in the next 10 years If the risk of major osteo porotic acture is greater than or equa to 20% or the risk of hp
ow Boe Mea Desy ssocaos
Lifestyle
Comorbid Illness
Hormona States
edicatons
Nonmodifable Risk Factors
Alcoo use
Vitami D isiciecy
Premature menopase
Acovulsans
ace
BMI <17
Hypercalciria Osteogeesis ieect
Glucocoicoids (�5 mg/d of pednisone or equvaet o 3 mots)
Age
Low cacum inake
Prematre ovarian isuicecy Hyperolactiemia
G atagoiss ad agonss
Androge isuicency
Firs-degee elative wit ow bone meal densty
SSs
Tyotoxcosis
Thazoldnedoes
Smog
Homocysnua
Immobiization
Hemocomaosis
Weg loss
Gycogen soage disease
Malabsortive baatic sugery
Panhypopitarism
Cystic iboss
Aromatase inbos
Gasc bypass sugey
Ceiac dsease
Ancoaguans
Recrent as
ushng syndoe
ium
Gede
amaoy bowe disease iabees elits (yes ad 2) GnRH = gonadotropi-releasng hormone; SSRI = selectve seroto reutake btor.
67
Calium n d Bon e Disorders
TABLE 34. US Peventve Sece Tk Fce Recendn f Meeen f Bne M ne eny nd Veeb Igng Bne Mne eny Teng•
Women age 65 and older and men age 70 and ode Postmenopausa women and men age 50 o 69, based on risk aco pofie Those who have had a ace o deemine degree o disease seveity Radiogaph fndngs suggesive of osteoporosis or veeal deformy Glcococoid heapy o moe han 3 monhs Prma hyperparahyodsm eamen o osteopooss o mono heapeuic response) ee gngb
Women �70 and men 80 T score a te spine oa hp o emoal nec is -1.0 Women aged 6569 and men aged 579 fscore at he spine ota hp or femoal neck s 15 In posmenopasal women age 5064 and men aged 5069 with he oowing isk actors: Lowama ares Hisoic heigh loss o 5 in or more (4 cm) Heigh oss o 08 nches o moe 2 cm) ecent or ongoing longtem gucocoicoid teatment •BMD testing hould be perfrmed at DEXA facilities sig accptd qaity assurance meases. bVereral iagg should e epeated wen a new loss of hegh s oed o new ack pan s epoe
q % ' x F 0 0 O F /F BMD DEXA O Evauation of Secondary Causes of Bone Mera Densty Loss M x x S M x D 68
BMD BMD BMD BMD q DEXA BMD Pharmacologic Treament Optons C x FDA B NK B M F z Bisphosphonates B B D F . K // 2 A j A q o o s o s o BMD. D 0 000 / 00 / .
Calcum and Bone Disordes
Alendronate has been approved by he FDA r preven tion and treatment of osteoporosis. The prevention dose s a 5-mg tablet daily or a 35-mg tablet weekl he treatment dose is a 0-mg tablet daily or a 70-mg tablet weekly. Alendronae is aso approved r reatment of men wth osteoporosis as wel as treatment of both women and men with gucocoticoid induced osteoporosis Alendronate has been shown to reduce he incidence of spine and hip actures by approxmaely SO% over 3 years in paents with previous f a ctures bandronate is FDA approved r the treatment and pre vention of postmenopausa osteopoross he dosage s a 150-mg tablet monthly or 3 mg every 3 months by intravenous injecton There is FDA approval r the oral rmuation r oseoporosis prevention onl bandronate primarily reduces rsk of vertebral f a cures by 50% in 3 years Risedronate is FDA approved r he prevention and treat ment of osteoporosis. The reatment dose is a 5mg tabet dail, a 35-mg table weekl, a 75-mg tablet on wo consecutive days every monh or a 50mg table monthl Risedronae is aso approved r treamen of osteopoross in men and women with glucocorticoid-nduced osteoporosis Risedronate reduces the incidence of vertebral acture by approximaely 45% and nonverebral actures by onehird over 3 years Zoledronic acid has been FDA approved r he preven tion and treatment of postmenopausal osteoporosis n women r mprovemen of bone mass in men with osteoporosis and r he prevenion and treatment of glucocorticod-induced osteoporosis in men and women Recently zoledronic acid has been approved r secondary prevenion of fracures in patiens who have had recent low-trauma hip racture. The reatment dose of zoledronic acid is 5 mg ntravenousy annu ally or once every 2 years r prevention. Calcitonin Cacitonin is DA approved r the treament of osteopoross n women who are Sor more years posmenopausal Calcitonn (200 U) is delivered in a single daily intranasal spray ubcutaneous administration is also avaiabe but is used ess f equently Cacitonin shoud be used with cauton wih patients who have an aller to salmon, alergic rhnitis or epstaxis. Vey rarely paents can also have an anaphyactic response that requires emergency atention and discontinua tion of the medication. Estrogen Agonists and Antagonists The use of estrogen to maintan bone healh in postmenopau sal women has llen out of vor because of data indcang that esrogen increases the risk of cardiovascular dsease and breast cancer. Therere estrogen use r oseopoross preven tion should be limted to younger women wih premature ovarian ilure and postmenopausal women who also requre is benecial eects r hot ushes or vagnal dryness Raloxine has been approved r the reatment of post menopausal osteoporosis The treatment dose s a 60-mg tab let to be taken with or without od
Parathyid Hormone Teriparatide recombnant human PTH [-3]) has been FDA approved r the treatment of osteoporosis in postmenopausal women and men who are at high risk r acture "High risk is dened as paents with a T score of -30 or less or patiens who have either had a acture or decreased BMD while on bisphosphonate therap It is aso approved r men and women at high rsk of acure due to long-time glucocorticoid use eriparatide has bone-buldng properies in addition to the antiresorptive properies of he other agents It is the only bone-building treament option r osteoporosis Teriparatide s an anabolic steroid hat s adminstered by a 20-µg daly subcutaneous inection; it is approved r up to 24 months over a patent's ifetime. After he 24-month dura ion, an antiresorptve agent (such as bisphosphonates or den osumab) can be administered to maintain BMD gains achieved with teriparatide Receptor Activator of Nucear Factor KB (RAN) Ligand Inhibitors Denosumab is a receptor acvator of nuclear ctor B (RANK) igand nhibitors that s FDA approved r the reatment of osteoporosis in postmenopausal women who are at high rsk of racture It is an antiresorptive agen like the bisphospho nates wth much the same eect and outcomes. t is also approved r treatment of osteoporosis in men and those undergong treatment of cerain cancers, such as prosate can cer who are at hgh risk r actures Denosumab s given by subcutaneous inecon 60 mg evey 6 monhs) Aual Reassessment of Paiens wih Low Bone Mass
nce an initial DEXA scan has been obtained, every efort should be made to have subsequent scans done on the same machine nce a repea scan has been done change n BMD, not score om year to year is the appropriate way to inter pret whether there has been a signicant change in BMD Mos reports will not show a statistcaly signicant change in the BMD om the previous test If no noted on the repor, a cal cuated change of about % likely represents a statistically signicant change Annuall, a complete clinical evauation of the patien deerminaion of risk ctors r bone oss and evaluaton r development of secondary causes of bone loss should be perrmed, starting with a history and physica examination.
Vitamn D Defcency In promoting absorption om the gut vitamin D enables proper bone mineralzation by mantenance of calcum and phospho rus evels Viamin D also moduates the actions of osteobasts and osteocasts to ensure proper bone growth and remodeng Chroncally low levels of vitamin D can lead to rckets in chil dren and osteomalacia in aduts (see MKAP 7 Nephroo) In addition to bone healh viamin D plays a role in inammaton reducion growth regulation of various cel types immune funcon and neuromuscular signaling. 69
Calcum and Bone Disorders
In assessing serum levels of vitamin D, concentraions of 25-hydroxyvitamin D are the best indicator of vitamin D sta tus. I reecs viamin D produced cutaneously and tha obtaned om od and supplements and has a circulating hal lie o 15 days. There are three leves of vtamin D status: suffcient (25-hydroxyitamin D 30 ng/mL [75 nmol/L], insucient (25-hydroyitamin D 21-29 ng/mL [52.4-72.4 nmol/L] and defcient (25-hydroxyitamn D 20 ng/mL [50 nmolL] Because vitamin D levels can be afected by sun exposure ll through wnter months are ideal times o measure vitamin D levels It s bes o measure vitamin D levels at the same time each year unless treamen s being folowed In general, the optimal leves o vitamin D are those that prevent PTH levels from increasing to above normal evels. Increased TH levels wl ead to increased calcium withdrawal rom the bones In an atempt to nd the optimal vamin D evel, several studes have looked at viamin D levels relaed to cancer incidence, muscle stability and lls immune status, and mood in addi ton to bone health. Among most expers a level beween 30 and 40 ng/m 75-100 nmo/L s deemed sufcent r pre ventive health Based on these levels, about 30% to 60% of Amercans have low vitamin D levels, therere most exper groups recommend screening all patien ts at least once. Those with darker skn, decreased sun exposure or increased demands (pregnancy) oten have low leves. Specia populaions will have lower levels of vtamin D owing to medical conditions or medication side eecs. In addi tion obesity has been correlated with lower vitamin D evels possiby elated to t sequestration. Certan antiseizure medica tions (phenobarbtal and phenytoin may increase the metabo sm of vitamin D to inactive rms. Glucocoricoids can decrease vitamin D metabolism Agents that decrease absopion such as orlistat and cholestero lowering agents can decrease vitamin D absorpton Similarl, patients wth malabsopton disorders includng hose with celiac dsease and those who had bariaric surger, can have decreased evels of vitamin D. n these special patient popuations not only does screening for decency need o be more equent, but repletion may be more challenging. It is recommended that these popuations be given at least wo to three times more vitamin D to maintain adequate leves Recommendations
The current Nationa Oseopoross Foundation andEndocrine Sociey recommendation r adults 19 to 70 years o age is at eas 600 U/d o vitamin D to maximie bone heah howeer to raise blood levels consistently above 30 ng/d (7 nmol/} may require 1500 to 2000 /d In adults older han 70 years of age 800 of supplemenal vitamin D per day s recom mended to maximie bone health; however 500 to 2000 /d may be requred to keep levels consistently above 30 ng/d 75 nmol/. In treating the decient patient 50000 of either ergocalcferol or cholecaciferol is recommended, once weekly r weeks. Once suciency s atained, maintenance therapy of 1500 to 2000 /d is recommended 70
Vitamin D toxicity s a very rare entity bu one to be aware o The efects of vitamin D levels greater than 90 ng/mL 225 nmol/L include hypercalcemia As a t-soluble vitamin, decreasng vtamin D levels that are once elevated can be a slow process requirng continued monitoring. KEY POINTS
• The .S. reventive Services Task orce recommends screening r osteopoross in women aged 65 years and oder and in younger women whose actue sk is equa to or greater than that o a 65year old white women who has no additional risk ctors • The pesence of a veebral compression acture makes the clinical diagnosis of osteoporosis regardless of Tscore on dual-ener x-ay absoptiometry (DX scan, and treatment is recommended • acure Risk Assessment Tool RX) score can help ident which patients ae most lkely to benet om osteopoosis treatment bisphosphonate theapy s st ine therapy r postmenopausal osteopoosis treatment and prevention • A 25-hydroxyitamin D evel between 30 and 40 ng/mL (75-100 nmo!/L is d eemed suffcient r bone health most expert groups recommend screening all goups at least once r evidence o defciency since .S inci dence is 30% to 60% of the population, howeve , it shoud not be a serial, recuing screening test
Paget Disease of Bone aget disease of bone is characterized by rapid and chaotic bone remodeling leading to disorganized bone microarchitec ture Ths disease more commonly aects persons ofEuropea n descent during the sixh decade with a prevaence of 3% to 10% n the elderly. aramyxovirus infecion of oseoclasic precursors is thought to be one possible cause, although about 15% o peope wth aget disease have a mily member with the disease. aget dsease appears to be inherited in an autoso mal domnant manner with ncomplete penetrance Clinical Presentation
The most common clnical manifestaion is asymptomatic elevated serum aaline phosphaase levels only 30% of patients have symptoms at diagnosis In some patients the dysnctional bone srucure creates expansion in the bone leadin to an, swelin, and warmt ones o t aial sel eton are most fequently afected namely the pelvis (70%, femur (55%), lumbar spine (53% skul (42% and tibia (30%) As a result patiens tend to have headache sensorineural hearing loss, and bowing of the long bones (Fige 16). The abnormal bone growth may aso lead to nerve impngement causing pain or neurologic defcits Rarely, patients can develop increased vascular shunting to bones with resultant rghtsided heart ilure, cellular transrmation to osteosar coma and hypercalcemia of immobilzaion
Bibliography
Bibliography
FIGURE 16. Radiograph showing Paget disease of bone in he le ateal iba of a 71-year-o woman. Noe e aneior boe, corica ikening and boe elargeme as ompae wi he ormal adogap o e ig Te log-sandg Page disease resule i a lef eg a was 25 c (1 i) sorter tha e rigt
Diagnosis The diagnosis of Paget disease should be suspeced n asymp omac paiens wth an solaed elevaton of akaline phos phaase wihou evidence of liver disease. In hese paiens he mos sensiive tes is a nuclear bone scan which wl deec areas of increased meaboic acivt Plain films of these areas should be obained o den pahognomonic pageic lesons such as cal oseoysis wih coarsenng of he rabecuar paern and cortical hickening. n sympomatic paens with bone pain, plain films of painu areas may be he iniial imagng test, alhough many expers recommend a baseline bone scan once he diagnosis is confirmed prior to iniiang reamen. Treatment The man herapies r Page disease of bone are the nirogen conaining bisphosphonae medicaions (alendronae pamdronate, rsedronae and zoedronic acid). he main ndicaions r aniresorpive herapy are (1) pain caused by he increased meaboic aciviy; 2) panned surgery at site of pageic bone disease and (3) hypercalcema due to muliple aected sites There is no evid ence ha antiresorpive herapy is benecial in asympomaic patens These medicaions are ideal because hey suppress he rapd bone urnover hat s characterisic of Page dsease. Decreases in alaine phos phaase can be noed wihin 10 to 14 days aer he iniiaton o herapy wih a nadr reached in 3 to 6 monhs NSA!Ds and anineuropahic medicaions can also be used r pan conro in hese patiens. For paiens wih pseudofacures orthope dic stabilzaion may be required KY PONTS
• he mos common clinical maniesaion of Page dis s s sym v s phae levels • he main herapy r Page disease of bone is he nirogen-conaining bisphosphonae medicaions (aendronae pamidronae risedronae, and zole dronic acid)
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Barber RL Mais A Randall RW Daniels G istner RW Ryan KJ Insln smlaes androgen acculatio n ncubaons of ovaran stoma obaned fo women wi hyperandrogenism J Cln Endocrnol Meab. 986 May62(5):90410 [PMI: 351465 Belvisi L Bobel , Sroni L Doldi N Oganspecc atoimmniy n patients wh premaue ovarian ire. Endocrinol nves. 993 Dec6():88992 PMID: 8144865 de Moraes Ruesen M Blizzard RM GacaBunel R, Jones GS. Atomuniy and ovaran ure A Obset Gynecol. 1972 Mar12(5)693703 [ PMID: 455032 Fernde-Balsels MM Muad M Lane M e al. Clnical review 1 Adverse eects of testoserone terpy n adut en a sysematc evew an d ea analysis J Cl Edocrnol Meab 200 un95(6):256075 [PMID: 20525906] Hoe A Schoemaker J Drehage HA Preate ovaran re and ovaran atoimnity En docr Rev 99 eb;8():1034 PMD: 9034788 Kaman R CastacaneVD Pemature ovaran ilre assocated wi auo me polyglandua syndome pahophysioogica mechaniss and fte fert J Woens ea (Lach) 2003 un12(5):53-20 [PMD: 12869299] Kong M, efcoate ghty-si cases of Addso's dsease C Endocinol (Ox. 994 Dec4(6):7576 [PMD 788961] egro RS, Banhart HX Scaff W e al Cooperative Mltcener Repodcve Medcine Nework Clophene merin, or bo ifetty n the poycystic ovay syndome N ngl Med 2007 Feb 8356(6):55-66. [PMD: 17287476 Mgnot M Scoemaker J leingeld M Rao BR Dexhage HA Pematre ovaan ure : The associaon wih atoimunty Eu J Obste Gynecol Reprod Bo 989 Jan30(1):5966 PMID: 2647538] Moncayo-Naveda H, Moncayo R Benz R Wolf A Lauizen C Ogan-specc antibodes against ovay in paets wth systemic upus eytematosus A Obste Gyneco. 1989 May;60(5 Pt 1)1227-9 PMD: 2729399] Pymae SR Matej LA Jones R Fredl K Inbion of se ooe-bindng globuln prducion in te human epaoa (Hep G2) ce lne by isuin and prolactin J Clin ndocol Meab. 988 Sep;67(3)4604 PMD: 2842359] Ryan MM Jones R Myashenia gavis and prematre ovaran lue Musce Nerve 2004 Au30(2):23-3 [PMID: 15266640] Vigen R O'Doel CI Barn A et al Associaion of testoseoe theapy wth moraty, myocardal nrction, and sroke in men wih low testos eone leves AMA 203 No 6310():82936. ram in: JAMA 204 Mar 531(9):967 PMD: 24193080 Cu d AlAzem H Khan AA. Hypoparayoidism Best Pac Res Clin ndocinol Metab 202 Aug26(4):51722. PMID: 22863393 Bscoff erar H A Wilet WC Oav E J et a A pooled analysis of viamn D dose reqiremens fo acre prevention N ngl J Med. 2012 Jl 5367(1):409. [PMD 22762317] Hck MF Vitami D deficecy N ngl J Med 2007 J 19357(3)26681 [PMD: 7634462] lck MF, Biney N Bschof errar HA e al Evauaon teaten and peventon of vamn D decency: an Endocne Socety clnca pracce guideline Cli n docrino Metab 2011 ul96():1930 [PMID 21646368] Macocci C Cetani Pmay hypepaathyrodsm N Engl J Med 201 Dec 22365(25)2389-97 PMID: 22187986] nstue o Medcne. Deta y Reference nakes r Cac and Vitamn D. Wasington, DC: National Academy Pess, 200. Naonal Osteopoross Foundation Clincan's Guide to Peveton and reatment of Oseopooss Washington, DC: Natonal Oseopoosis Fondaon 204. Rason SH Page's disease of he bone. N ngl J Med. 203 eb 14368(7):64450 [PMID: 23406029] Shama O Hypecacea in ga nuoatos dsordes: a cncal review C Opn Plm Med 2000 Sep6(5):4427 [PMD 0958237 Shobac D Hypopathyodism N Engl J Med. 2008 Jl 24359(4:391403 [PMD: 1865055] Wolpowtz D Gichres BA The vtan D qestons: how much do yo need and ow sould yo ge i? A Acad Dermato 2006 Feb542):30117. [PMD: 1644306
Endocrinology and Metabolism Self-Assessment Test is self assessment test contains one-best-answer mutipechoice questions. Pease read these directions caefuy bere answering the questions. Answers, criiques and bibiographies immediatey ow these mutipechoice questions he American Coege o hysicians is accredited by the Accreditation Counci r Continuing Medica Education (ACCME) to provide continuing medica education r physicians e Ameican Coege of Physicians designates MKSAP 17 Endocrinolog and Metabolism fr a maximum of4 AMA PRA Category 1 TM _ Physicians shoud caim ony the credit commensurate with the extent of their partici pation in the activity
Earn "Instantaneous CME Credits Online int subscibes can ente thei answes onine to ean CME credits instantaneousy You can submit your answers using onine answe sheets that ae povided at mksapacponineorg where a ecord o your MKSA 7 credits wi be avaiabe To earn CME credits you need to answer a of the questions in a test and earn a score of at east 50% corect number of correct answers divided by the tota number of questions Take any of the fowing approaches: � Use the printed answer sheet at the back of this book to record your answers Go to mksap.acponineorg access the appropriate onine answer sheet, transcribe your answers and submit your test instantaneous CE credits. here is no additiona fee fr this service � Go to mksapacponine.org access the appropriate onine answer sheet directy enter your answers, and submit you test f instantaneous CME credits. ere is no additiona fee fr this sevice � ay a $5 pocessing ee pe answer sheet and submit the printed answer sheet at the back of ths book by mai or fx as instructed on the answer sheet. Make sure you cacuate your score and x the answer sheet to 25352799 or mai the answer sheet to Member and Customer Service Ameican Coege of Physicians 90 N Independence Ma West Phiadephia PA 906572 using the courtesy enveope provided in your KSAP 7 sipcase You wi need your 0-digit order number and 8-digit ACP ID number which are printed on your packing sip Pease aow to 6 weeks r your score report to be emaied back to you Be sue to incude your emai address r a response If you do not have a O-digit order number and 8-digit ACP ID number or f you need hep creatig a username and passwod to access the MKSA 7 onine answer sheets go to mksapacponine.org or emai custsev@acponieorg. CME credit is avaiabe om the pubication date of December 3 205 unti December 3 208 You may submit your answer sheets a any time during this period.
73
Direcons Each of the numbered items s llowed by letered answers. Select the
ONE letered answer that s BES n each case.
Item 1
Item 3
A 23yeaod woman s evauaed because of a week hs ory of papaons. She aso repos some hea noerance and md anxey during he as several weeks, bu she oth erwse fees wel. She is n the rs rmeser of an otherwse uncompcaed rs pegnancy. He ony medcaton s a prenaa vamn. On physca examnaon she is afebe, bood pres sue s 0/72 mm Hg pulse rae s 05/mn and resp raon rae s 3/min. BM! s 20. e skn s warm and mos. ere s no proposs o d ag Examnaon of he neck shows a dusey enarged hyrod wh an audble bru ove boh obes. Cardopumonary and abdomna examnaons are unremarkable Neuroogc examna ton eveas a ne resng remor of he hands and brsk reexes.
A 31-year-old woman is evaluated owng he recen dscovery tha she s pregnan a approxmaey 0 weeks' gesaton. Medca hstory s sgncan r a poacnoma dagnosed 2 years ago durng an evauaon fr amenor rhea A the me of dagnoss, her serum proacn eve was 84 ng/mL (84 µg/L), and a 4-cm puary adenoma exending above he sea was deeced on MRI wihou evdence o mass eec. She was treaed wh bromocrp tne wth reun o regular menses. She dsconnued he bromocrpne when she und tha she was pregnan. She s cuenty wihou sympoms. She does no have new or severe headache. Medca history s otherwse unre markabe and her ony curren medicaon is a prenaa mulviamn On physca examinaton, va sgns are norma. Vsua eds are ful o confontaon and he remander o her examnaon s norma
Laboto studies:
yrod-smuaing hormone Fee hyroxne (T ) Toa rodohyonine (T} hyrod-smuatng mmunoglobun index 4
<0008 µU/m (0.008 mU/) 5.5 ng/dL (709 pmo/) 400 ng/d (6.2 nmo/) 4.5 (norma <.3)
ich of he owing is the most appopiae t reamen?
(A) (B) (C) (D)
Mehimazoe Propyhouac Radoacve odine hyrodecomy
Item 2
A 34-yeaod man s evauaed esodc palptaons o 8 monhs duraon e palptatons as 5 o 0 mnutes and hen resove spontaneousy. ey are usualy assocaed wh sweang and anxey. Medca hisory s sgncan r hyrodecomy r meduay hyrod carcnoma dagnosed a 2 years of age. Hs her has aso undergone hyrodec omy r meduary hyod cancer. Hs ony medcaton s levohyroxne On physcal examnaon blood pessure s 64/ 92 mm Hg puse rae s 06/mn and respraon rae s 2/ mn. Auscuaon of he hear reveas a regua achycadia whou murmus. he emander of his examnaon is unremarkabe. aboraory sudes show a 24-hour urne exceon of caechoamnes of 30 µg/m 2/24 h (832 nmol/m/24 h) and meanephrnes of 3400 µg/24 h (7238 nmo/24 h). In addition o the presenting diagnosis, which of e low n soers s s pa en os kely o deveop?
(A) (B) (C) (D)
nsunoma Neurobroma Prmary hyperparahyrodsm Proacnoma
Which of he owing is the most appopriae nex sep in managemen?
(A) (B) (C) (D)
Check serum proacn eve orma visua ed estng Repea tuary R Restar bromocrpne
Item 4
A 48-yea-od woman returns r a ow-up vs fr man agemen of ype dabees meus. She epors dong we snce he as vs. Overa she beeves tha mos of her bood gucose eves are a goa, bu s concerned abou occa sona episodes of hypergycema occuring n he morning bere breaks. She eas a bedme snack every ngh ha s no covered wh meame nsun. Revew of her bood gucose og demonsrates monng sng bood gucose vaues rom 80 o 90 mg/d (4.4-0.5 mmol/). Her oher premea and bedme vaues range om 00 to 20 mg/d (5.56.7 mmo/) She execses wo o hree tmes per week in the evening. edca hisory s sgncant r hyperen son and hyperpdema Medcaons are nsun gargne nsuln spro, ram pr simvasan, and asprn. On physcal examnaton, bood pressure s 130/72 mm Hg and puse rae s 67/mn. BM! s 24. he remander of he examinaon is unremarkabe. Resuls of aboraory sudes show a hemoglobn A eve o 6.9% and serum creainne eve of .0 mg/d (88.4 µmo/) Serum eecroyes are noma. 1
c
Which of the owing is he mos appropiae managen o s an's oasona sn ypelycema
(A) (B) (C) (D) (E)
Add nsuln spro at bedtme Add metrmin Increase nsun gargne dose Measure 3 AM blood gucose eve Contnue curren regmen 75
Self-Assessment Test
Item 5
A 70-year-od woman is seen r llow-up evauaton r possible Cushing syndrome. She presented with new-onset diabetes meltus and a 9.1-kg (20-lb) weight gain over the last 6 months Medical hstory is otherwse unremarkabe, and she s currently takng no medcations and has had no exposure to exogenous glucocorticoids in the past year. On physical examination blood pressure is 160/90 mm Hg, pulse rate is 80/mn, and respration rate is 12/ min BM s 30 Facial plethora , central obesity, and bilat eral supracavicular t pads are noted ere are viola ceous abdominal striae measuring 1 cm wde and mutipe ecchymoses on the extremties Initial laboatoy studies show a serum cortisol leve of 9 µg/d (248.4 nmolL} lowing a 1-mg dose of dexameth asone the night bere, and a 24-hour urine fee cortisol eve that is greter than 3 tmes the upper limit of normal, which is conmed on a second measurement. A plasma adrenocorticotropic hormone (ACTH) level is undetectable Which of the llowing is the most appropriate diaostic test to perorm next?
(A) (B) (C) (D)
CT scan of the adrenal glands nferior petrosal sinus sampng Late night salivary cortisol measurement MR of the pitutary gland
Item 6
A 44-year-old man s evaluated r management of type 2 diabetes mellitus He was dagnosed with diabees 6 months ago after being admtted to the hospital with diabetic keto acidosis He was discharged om he hospital on a basal and preprandal insun regimen. Medcations are regular insulin bere meas and neutral protamne Hagedorn (NPH) insulin at bedtime He competed dabetes education and nutrition casses and has been adherent with liestye modicatons His nsun doses have been decreased graduay over the ast 4 to 5 months. His most recent hemoglobn A level is 6.7% Blood glucose values om his log book average 130 mg/dL (72 mmol!L) On physca examination, temperature is 37.2 ° (990 °F) blood pressure s 128/68 mm Hg and pulse rate is 72/mn BM is 30 His physical examinaton s unremakable. Laboratory studies at the time o hospita amission:
Glucose, f sting Antbody to glutamc acd decarboxylase 65 (GAD-65) Antibody to slet antigen ( C-peptide, sting
825 mg/dL (45.8 mmol/L egative Negatve 0.5 ng/mL (016 nmol!L) Normal ange: 083. ng/mL (02603 nmol!L)
Whch o the lowing is the most appropriate next step in his management?
(A) Dscontinue current insulin regmen initate sidng scae insuin (B) Discontinue nsulin initiate metfmn 76
(C) Repeat measurement of antibodies to glutamc acd decarboxyase 65 and islet antigen 2 (D) Repeat measurement o stng C-peptide and glucose eves tem 7
ye od n s ed n h ency e n e 'ws h y ·· cd s y wiu wg s d ld hehes e s ys bu ng s see S e e de bgn e st is s e ye e sin n his g ey bee blu d eegency te is ed sy s sinn ogss el ysunc n lss b the s yes O ys ei emerure s ( ) bl esse s 6/92 g se is 0/ n sn is / M s 8 He s ss sn i his l y in th u qs hs ig ey e ls s e y ss Oh s c eng n sesn xeies e r s s seec g o he e shws u puy mh u y MI shws - iy ss w n ehg ss coesses he tc hs d e e eus snus Ater administering high-dose gluc ocorticoids , whic h o the llowing is the most appropriate immediate management?
(A ( (C (D
ssess ity e n n es g nssphen decei W rn exel be din
tem 8
A 42-yea-old woman s evaluated during an annual physical examinaton. She fees well She has no perti nent personal or f mily medical history, and she takes no medcations. On physical examination, vital signs are normal Pal paton of the thyroid reveals a possible nodule in the right obe that is not mobile with swallowing. he remander of the gland is unremarkable and there is no palpabe cervical lymphadenopathy. Other physcal examination ndngs are normal Laboratory studies reveal a serum thyroid-stimulatng hormone level of7 µUmL (.7 mU/L) u w -m nodule with nternal microcaccations Wich o the owing is the most appropriate next s tep in management?
(A) (B) (C) () (E)
CT wth contrast of the neck Fine-needle aspiration of the nodule Levothyroxine therapy Measurement of serum thyroglobuln eve yrid scan with technetium
C
Self-Assessment Test
Item 9
An 18-year-old woman is evaluaed r primary amenor rhea. Her cogniive function is normal, and she is no sex ually active Her persona and miy medical hisory is unremarkable She aes no medicaions On physical examination, emperaure is 36 °C (970 °F), blood pressure is 110/70 mm Hg, pulse rae is 7/min, and respiraion rae is 16/min; BM! is 20 Her heigh is 147 cm (58 in) Physical examinaion and secondary sex characer istics are normal, wih Tanner sage IV breas and pubic hair developmen Pregnancy esing is negative On subsequen lab oraory sudies esradiol level was undeecable serum folliclesimulaing hormone level is 7 mU/mL (7 U/L}, and serum lueinizing hormone level is 46 mU/mL (46 U/L} Which o h owig i h o appopia aag ?
(A) (B) (C) (D)
Iniiae esrogen and progesin herapy Measure serum proacin Measure hyroid-simulaing hormone Perrm piuiary MR
Item 10
A 32-year-old man is evaluaed r a 1-wee hisory of severe nec pain He also has hea inolerance papiaions and insomnia Medical hisory is signican only r a vira pper respiraory rac infecion 3 wees ago He taes no medicaions On physica examinaion, he appears anxious and is sweaing here is no proposis or id lag Examinaion of the thyroid reveals a normal-sized gland ha is very ender to palpaion here are no hyroid nodules he hear rae is regular bu achycardic e lungs are clear Laboaoy ud:
hyroid-simulaing hormone Free hyroxine (T.) Toal riiodohyronine (T) hyroid-simulating immunoglobulin index 4Hour radioacive iodine upae
<0008 µU/mL (0008 mU/L} 3 ngdL (413 pmo/L 310 ngdL (48 nmol/L} <13 (normal <13) 5% (low)
Which o h owig i h o appropia a?
(A) (B) (C) (D}
Mehimazole Meoprolol Propylhiouracil Radioacive iodine
twice Her las mensrual period was 4 monhs ago She also notes low libido nd dyspareunia She has no had weigh changes, constipation hair oss or hirsuism, or sin changes Her medical hisoy is signican r primay hypothy roidism and bipolar disorder Medicaions are levothyrox ine, lihium and risperidone She repors tha she has been stabe on hese medicaions fr a few years and feels well She plans o discuss her medicaions wih her psychiaris prior o pregnancy On physical examination bood pressure is 118/72 mm Hg and pulse rae is 82/min BM! is 24 e hyroid is normal isual elds are inac Laboaoy ud
Folicle-stimulaing hormone Lueinizing hormone Prolactin yroid-simuaing hormone
3 mU/mL (13 U/L} 20 mU/mL (20 UL) 10 ng/mL (102 µg/L} 11 µU/mL (11 mU/L}
Which o h owg i h o iky cau o h hyppoaciia?
(A) (B) (C) (D)
Hypohyroidism Lihium Piuiay adenoma Risperidone
Item 2
A 55-year-old woman is evaluaed r a new-paien visi Medical histoy is signican r an eating disorder Alhough she has maintained a normal weigh r the past 20 years, she noes ha prior o ha ime her weigh would lucuae in a range correaing with BM!s of 17 to 19 She has oherwise been healhy and currenly feels wel She is posmenopausal and a neversmoer Family hisoy is signican r posmenopausal oseoporosis in her moher Her medicaions are over-he-couner calcium and viamin D supplemens On physica examination, emperaure is 363 ° (973 °F} blood pressure is 137/81 mm Hg, pulse rae is 76/min and respiraion rae is 1/min BM! is 1 She has mild horacic yphosis bu no seetal enderness e remainder of he examinaion is unremarable Results of laboraory sudies are signican r a serum calcium level of 91 mg/dL (23 mmol/L} and 25-hydroxyvi amin D level of 40 ng/mL (998 nmol/L} hyroid funcion sudies are normal Dual-energy x-ray absorpiomery (DEXA) scan shows T-scores of 1.8 in he femoral nec and 19 in he lumbar spine Tenyear acure ris using the Fracure Ris Assess men Tool (FRX) is 69% r major oseoporoic acure and 07% r hip acure Plain radiographs of he spine show no evidence of compression acure
tem 1
o ow o roa aa o h pa?
A 30yearold woman is evaluaed for amenorrhea She and her husband are interesed in pregnancy in he nex year and hey are concerned ha hey will no be able o conceive Her menses became irregular abou 2 years ago In he pas monhs, she has had menses
(A) (B) (C) (D)
Begin raloxifene Repea DEXA scan in 2 years Repace calcium wih cholecalcifero Star bisphosphonae herapy 77
Self-Assessment Test
Item 13
- ICU ' b e O 88 ° (8 / . / · e -z O - U U ( o 8 W g s s s s s ( (B ( (
E G e e
°
°
g g? A) B) C) D)
Parathyroid sestamibi scan Refe or parathyoidectomy Switch to vtamin 3 cholecacfeol) Tissue transglutaminase antibody testing
Item 16
Item 4
A 43-yearold man s evaluated duing a low-up visit r management of type 1 dabetes mellitus. He was diagnosed at 1 years of age and has mulipe chronic complaions rom his diabetes, including end-stage kidney disease requiring hemodiaysis, gastroparesis, equent hypoglycemia with hypogycemic unawaeness, painl periphera neuopathy, and proliferative retnopathy e patient uses an insulin pump and a contnuous glucose monitoing system to man age his dabetes. He is adherent with his regimen and per ms multpe ngerstck blood gucose measurements with values rangng from 65 to 250 mg/d 36-139 mmol/L) Hs most recent hemoglobin A evel is 7.5% 1
weekly 6 weeks ago. Medical histoy is signicant fr vit iligo and chronic tigue Medcatons are vitamin 2 and calcium carbonate n physca examnation tempeature is 36. C 96.9 F), blood pressure s 132/71 mm Hg pulse rate is 3/min and espiration rate is 12/min. BM! s 9 he remainde of he examnation is unremarkable. : Calcum 9.1 mg/dL (23 mmol/L) Ceatinine 09 mgd (796 µmol/L) Parathyroid homone 10 pg/mL 01 ng/L) 25-Hydoxyvitamin 7 ng/m (175 nmol/) after 6 weeks 24Hour urine calcium 150 mg/24 h (3. mmol/24 h)
c
g g ? A) Ater nsuln pump settings to attain a hemoglobin A go of less than .0% B) Ater nsulin pump settngs to decrease the insuin doses C) Discontinue the insuln pump, start subcutaneous insulin injections (D) Stat gabapentn r treatment of painful periphera neuropathy
c
A 54-year-od woman s evauated because of ftgue. Although she lows a daly 400-kcal diet and exercises 3 to 4 nights per week fr 30 minutes, she has gained 2.3 kg 5.0 lb) n the last month. She has hypercholesterol emia reuirng statin therapy. Her mother was dagnosed with hypothyoidism shortly after the birh of her last child n physical exaination blood pressue is145/90 Hg pulse rate s 0/min, and BM is 25 he skin is dy he thyrod is dly enlarged with a disely nodular textue No discrete thyroid nodules are palpated Reexes are norma. : hyoid-stmulating hormone 65 µ/mL 6.5 m/L) (TSH) Free thyroxine 09 ng/dL 116 pmol/L) yoid peroxidase antbody Postive Similar resuts r SH and T were obtained 4 months 4
ago
W g g? (A) (B) (C) (D)
ntiate evothyroxine therapy Measure thyroid-stimulatng immunoglobulins Repeat serum TSH measurement in 12 months Schedule thyroid radioactive iodne uptake and scan
tem 5
Item 17
A 55-yearold woman is seen in low-up ow bone mass and vitamin D deciency. Cortcal bone tinning was noted on radiographs of her right anke flowing a ll 3 months ago. Subsequent evauation ncuded a dual-energy x-ray absoptometr (DXA) scan showing osteopenia Her serum 25-hydroxyvtamin D evel is 4 ng/mL (0 nmol/L). She was stated on 50000 of vitamin D (ergocalciferol)
A 74-year-old woman is evaluated fr a diagnosis of pmay hyeparathyrodism made after an elevated seum calcium leve was incidental dscoveed on laboatory studies She has no symptoms assocated with hypercacemia Medical histoy is signcnt hperension and chonic kdn disease er only medication s amlodpine She has never smoked.
2
78
Self-Assessment Test
On physical examnation, temperate is 36.8 ° (98.3 °F) blood pressure s 34/87 mm Hg puse rate is 92/min and respiration rate is 4/min. BM! is 27 he remainder of her examination s unremarkable Laboatory sudes: Calcium Creatnine Parathyroid hormone Estimated glomerular ltraton rate
13 mg/dL (28 mmol/L) 3 mg/dL (14.9 µmolL) 6 pg/mL (76 ng/L) 40 mL/min/.3 m2
Dual-energy x-ray absorptiomety (DXA) scan shows a T-score of - 3 in he right femoral neck. Her racure Rsk Assessment Tool (RAX) score indicaes a 2.1% 0-year probabiity of hip acture and 7% 0-year probablty of any acture. Wich of the llowing is the most appropiae herapy to ecommend to ths patient?
(A) (B) (C) (D)
Alendronate Cnacalcet Parathyroidectomy Clnical observaton
hot ushes and tigue. She has noted galactorrhea She began having headaches 2 years ago. In addiion she notes blurry eriphera vison. e rest of her medcal hisoy s unremarkable. She takes no medicaions On physical examinaton blood pressure is 2/72 mm Hg and pulse rate is 68/min. BMI is 2. White miky substance is expressed om her breasts bilaterally Ocular movements and cranal neve s are intact. here are no stig maa of Cushing dsease or acromegaly Laboatoy studies: Cortisol 8 afte 1 mg of dexamethasone he night before Estradol ollicle-stimulating hormone Luteinizing hormone Prolactn yroid-stimulating hormone
6 µg/dL (44.6 nmol/L)
<32 pg/mL (7.4 pmol/L) m/mL (. U/L) 0.8 mU/mL (0.8 U/L) 472 ng/mL (472 µg/L) . µ/mL ( mUL)
MR shows a 2.4-cm pituitay tumor that elevates he oic chiasm and surrounds the left carotid artery Wch of he llowing is he most appopiate t eatment?
Item 18
A 74-year-old woman is evauated because of newonset anxety and insomnia. or the last 6 weeks she has been waking up muliple times each nigh She does not have heat ntoerance change in bowel habts palpitations or dyspnea on exertion She takes no medicaions. On physca examnation blood pressure is 25/68 m Hg and pulse rate is 89/min. BM! i s 8. here is no oosis or id lag. Examination of the thyroid reveals a 5-cm rm nodule in the left lobe that moves upward wih swalowing. A ne resing hand tremor is present biaterally Laboratory studies reveal a serum thyroid-stimulat ng hormone level of 0.05 µU/mL (0.05 mU/L) a serum free thyroxine (T,) level of 2.9 ng/dL (3.4 pmo/L) and a serum total triodothyronine (T leve of 250 ng/dL (3.8 nmo/L). Ultrasound of the neck shows two thyroid nodules a .5-cm nodule in the righ lobe and a 2.0-cm nodule in the left lobe. Wch of the llowng is the most app ropiae next sep in managemen?
(A) ine-needle aspiration of boh thyroid nodules (B) Initiation of methimazole (C) Radioacive iodine (123 ) uptake and scan of the hy roid (D) Total thyrodecomy
(A) (B) (C) (D)
Cabegoine Octeotide Radiaion Surgery
tem 20
e-o o eue i e eege er e ee o o' ee mea ss Se fo ouoe i sig ee. Oe o e og ee a ee l onet sos e e deeoe oe ds ago ad oig as go Se ee ue o oee qd o o os e a ou eda ito is sigic e es ete eie d o eico e aii sio ge e leoie os e a ose o e o a 8 ou o i eo e eee 7 °C oo eue s / g a se e i /i. Se s se u ose ucos ee e e ec se Ca e o ee o u e ce is e o su io o o se d eeess o o i oe o oe ·ee s o eo o ee e o c eog es oo sie e ei
Item 9
Whih of the owing s the mos kely cause o pa' ard a a?
A 34-year-od woman is evaluated r amenorrhea head ache and ftigue. She reports that from the time of menarche until 2.5 years ago he menses were regular and predictable Two and a half years ago her menses became irregular and hen stopped completely 6 monhs ago She has had a few
) CJ )
Cee e oge oi S oc 79
C
Self-Assessment Test
Item 21
A 38year-od woman is evaluated because of a 3-week history of palpitations She notes that her heart "races at nigh and aer minma exetion. She aso repor: ·�? intoerance but has no change n bowe habits or menses. On physical examination he paent is restless and has pressured speech. Temperature is 36.8 ° (982 °) blood pessure is 30/60 mm Hg pulse ate in /min, and respiration ate is 2min. Her skin is warm and moist and a blateral hand tremor is present. ere is no proptosis or lid lag. he thyroid is enlarged without nodules or bruits. Serum thyoid-stimulatng hormone level is 0.08 µU/ (0.08 mU/), and the serum fee thyroxine (T ) evel is 7 ng/d (29 pmol/).
with a round ce. She has terminal hairs on her chin, uppe ip, chest, and back Mild cial acne central obesity, and a few wide purple striae on the back of he ams are also noted She has supraclavicular t. Her skn has psorac pau es. Musce strenth in the upper and lower extremities is 4/5 Wich of the llowing is the most ikely diagnosis?
(A) (B) (C) ()
Adrenocortcal cacnoma Cushng disease Ectopic adrenocorticotropic hormone production atrogenic Cushing syndrome
4
Which of the lowing is the most appopriate net step in management?
(A) (B) (C) (D)
Measue serum tiiodothyronine (T) level Measure seum thyroid peroxidase antbody iter Repeat thyroid uncon tests in 6 weeks Schedule ultrasound o the neck
Item 22
A 34-yea-old woman is evaluated a diagnosis of hyper cacemia ater presentng to the emergency deparment 3 days ago treatment of a kidney stone. She presened with severe right lank pain wih nausea and vomitin A 2-mm kidney stone was idenied n he right ureter by utraso nography that passed sponaneously; mulpe addiional ntrarenal cacicaions were noted to be present. abora tory studies at that time showed normal kidney unction and a serum cacium level of 5 mg/d (2.9 mmol/). Med ical histoy is othewise sinican r hypertenson and sacoidoss. Her only medicaion is hydrochloothiazide. On physica examiation tempeature is 368 °C (982 °F) blood pessure is 38/87 mm H, puse rate s 89/min, and respiaion rate is 2 BM! is 32 he remander of he exam inaon is unemarkabe. aboaoy studies are signicant a parathyroid hormone eve of 4 pg/m (4 ng/) Wich of the llowing is most likely responsibe r causing this patient's hercalcemia?
(A) (B) (C) (D)
Calcium-sensing receptor mutation Elevated ,25dhydroxyviamin D eves 25Hydroxyvitamin D level hiazide-induced renal cacium eabsorpton
3
A 40yearod woman is evauated r amenorrhea of 4 monhs' duration She has had weight gan cial hai alopeca and debilitating tigue. Her medica histoy is signicant r psoasis. She seems to be gainin weight n her ce abdomen and neck She also bruises easily Her ony medcation is cobeaso r psoriass. On physica examinaton temperatue is 376 °C (997 °F) blood pressure is 48/90 mm Hg, pulse rate s 88/ min and respiation rate s 2/min. BM! s 38. She s obese 80
Item 24
woan is ed in een dp n a disia poyhi n n nnn in 5 (9b wih lss oer e ps onh h s h nsn ehy over he as 2 hos e isy an his nemaabe Sh s n icains n hs exinaion ear is 37.5 °C (99.5 °) l ss s 98/5111 ls ae s / in n sin e is 30/in BMI s 7 She is ehar i wi d s ebne hpnea n tachy i Chs austin is oinal ination sws s i neess nd nol bowe sns h s n en eness rin wih aain Laboatory stdes:
i oy n ss PC Cnn rys S11 Pssi Ci n Gs t
7 /L (7 /) /L ( 0/L) 75 111 (8 a 3 dL (9 mL) 30 q/ (3011L) 30 q (31/) 99 q/ (99 L) 9 q/L (9 1111/L /L (3 l/) 8 /L (0.89 /L
Inns 9Y san is iniatd thruh a cenr ens he n raio shws sins hyada 0/in Chs ih s n Which o the owing is the most appropriate next step n the management?
( (C (
inis nens eaxn nns oassi od inise inens soi bicne In nnos nsn r
Item 25
A 65year-old woman is evaluated llowing a ecent dag noss of osteoporosis discovered on a screening dual-enery xray absortiometry (DEXA) scan tha showed Tscores of 2.5 at the femora neck and 2.7 a the hip Ovea she
C
Self-Assessment Tes
feels well although she notes a 5-cm (2-in loss of heght over the past 15 years and a 2.3-kg (5-lb weght oss over the last yea. She s postmenopausal. Medcal istory s unremakabe and she is a neve-smoker. Family history is negative r osteopoross or nontraumatic fractures. She takes no medications. On physica examination, temperature is 36.8 ° (982 ) blood pressure s 144/68 mm Hg pulse rate s 92/ min, and espiration rate is 14/mn. BM! is 22. Te remander of the examination is unremarkable. Laboatory studies are sgncant r a normal basc metaboic proe and complete bood c ount Serum calcium is 9.5 mg/dL (24 mmol/L) and serum phosphous is 3.8 mg/ dL (1.2 mmol/L). Seum 25-hydroxyvitamin D eve is 32 ng/ dL (9.9 nmol/L). ch of the llowing tests is indicated prio to initiation ofphamacoogic theapy?
(A) (B) (C (D)
Serum and urine makers of bone turnover Serum estradiol level Serum parathyroid hormone leve Serum thyroid-stimulating hormone leve
Item 26
A 24-yea-old woman is evaluated for excessive men strual bleedng. She was recently diagnosed with polycys tic ovary syndrome during an evauaton for hirsutism Menarche occurred at age 11 years and she has always had irreguar menses occurring approximately every 60 days oweve, her periods over te past year have been associated with heavy bleedng that is inceasingly both ersome. Medical history s othewise unremarkable and she takes no medications She currently does not desire fertiity. On physical examination, she s afebrile Blood pres sure is 0/0 mm Hg pulse rate is 8/min and respiration rate is 14/min BM! is 32 Excess terminal hair growth s present on the upper lip chin and chest Te physical examnaton is otherwise normal. A urine pregnancy test s negative. hch of the llowing is the most appropiate theapy r this patient?
(A) (B (C) (D)
Combned oral contraceptive pils Levonogestrel intrauteine system Metrmin Perodic progestin withdrawal
Item 27
A 55-year-old man is evaluated r abdonal lness and nausea of 2 weeks' duration. He has no vomiting or fever One mont ago he was diagnosed with type 2 iabetes meitus. e reports an unintentional weigt oss o g ( lb) over the past month generalized weakness and poor appetite Metrmin is his ony medication. On physical examinaton, blood pressue is 158/90 mm Hg and pulse rate is 90/min. BM is 29. s fce is round and red. A dorsocervical fat pa is present. His abdomen is disended but nontende. Violaceous
striae measuing 8 to 12 mm wide are noted on his upper arms and abdomen. Thee s+ blatera lower extremity edema. Mutiple ecchymoses and acanthoss nigricans are present Laboatoy studies: Adrenocortcotropic 5 pg/mL (1 pmol/L) homone 24-our urine cortiso excretion nita measurement 280 g/24 (776 nmol/2 h) Repeat measurement 300 µg/24 h (826 nmol/24 h Cortisol serum 46 µg/dL (1269.6 nmol/L) Urine Catecholamines 40 µg/m 2/24 h (2364 nmo/m/ 24 h Metanephrines 1000 µg/24 h (5070 nmo/24 h) C scan of the abdomen with and wtout contrast eveals a 56-cm eterogeneous right adenal mass with fcal areas of calcications and hemorrage The density of the mass is Hounsed units and te contrast washout at 10 minutes is 20% hch ofthe owing is the most appropiate net step in the management ofthis patients adrenal mass?
(A (B (C (D)
Chemotherapy Fine-needle bopsy Radation theapy Surgcal excision
Item 28
i uu < I i 7 ( 7 I <e . j a i ( / / / q/ : / Q W " x ostc tes to vauae s pate's yocalceia?
( C (
- I l M 81
C
Self-Assessment Test
Item 29
A 52-yea-old woman presents fr llowup evaluation after being diagnosed with type 2 dabetes mellitus 6 weeks ago Her inital hemoglobin A 1c leve was 80% Management at ths tme is with listyle modcatons. She has woked closely wih a diabetes educator and a nuritonst since her dagnosis. She has lost 32 kg 7 lb by making changes to her det ad actvity level. Revew of her blood glucose og fr he past 2 weeks shows pepandial blood glucose values in he 150 to 160 mg/dL 8.38.9 mmol/L ) range and several -hou postprandal bood glucose values of 90 to 200 mg/dL (10.51. molL ). Her only other medcal problem is hyperension r which she takes isinopil. On physical examnation blood pressure is 125/70 mm Hg and pulse rate is 74/mn. BMI is 28. ee is no evidence of dabetc retnopathy She has nomal onolaent and vbratory sensaton n he extremites Except r her blood glucose parameters, basic labo atory sudes obtaned at the ime of her iniial dagnosis were normal In addition to continuing liestyle modications, which of the lowing is the most appopriate management this patients diabetes?
(A (B (C D
niiate dapaglozn ntate glpzide Initate etmn Intiate staglipin
A 28-yea-old man is evaluated fr fatigue and erectile dysfunction His symptoms have been pogessive over the past year. He noes decreased lbido and eports loss of morning erecions. He also feels tired has dculty concentrating and noes diuse jont aches He believes he has less strength and has had o decrease his level of exercse Medical histoy s unremarkable He had norma pubery and norma growth. He takes no medications On physical examiaon temperaue is 374 ° (993 °F blood pressure is 108/72 mm Hg, pulse rate is 68/in and respiraton rae s 4/in. BM! s 23 Te ive edge is pal pable 4 cm beow he costa magn. The penis is norma, and the eses are normal volume but sof and eely moble withou masses Visual elds ae inact. Laboratoy studies:
30 U/L 3.0 U/L ) 22 U/L 22 U/L 12 ng/ (1 µg/L) 178 /dL 2 nol/L 162 ng/dL 56 nol/L ) 2.3 U/L 2.3 U/L
Pituiary MRI is normal Wich o the lowing is the most appopiate next step in management?
A Begn testoseone replacement therapy (B Karyotyping 82
Item 31
A 59-yea-od man is evauated hypercalcema. He was recenly diagnosed with multiple myeloma He does not have anoexa, nausea, constipation poydipsia, polyuria or confusion. Medcal history is oherwise unremarkabe and he takes no medications On physical examinaton, temperature s 36.4 °C ( 975 °F) bood pressure is 134/80 mm Hg pulse rate is 80/ min and respiaon rae s 12/min. BM! is 30. Te remainder of his physical examination is nomal, and no weakness is noed on neurologic examination Serum calcium level is 108 mg/dL 2.7 mol/L ). Wich o the lowing is the most appopiate next aboatoy test evaluating this patient's hypecalcemia?
( A) (B) C) D)
25-Dihydroxyviamn D level Ionized calcium evel Paathyod hormone level Parathyoid homonerelated protein level
Item 32
Item 30
Folice-stmulatng hormone Luteinzing hormone Prolactn oeo total 8 AM) estosteone total 8 , repeated TIyrod-stiuating hormone
C) Serum ferritin leve and transferrin saturation D esticular ultrasound
A 37-yea-old man s evaluaed r a 2yea hisoy of low ibido, loss of morning eections tigue, and decreasing muscle mass His medical history is otherwse unremark able. He akes no medications. On physical examnation vtal signs are normal BM is 35 The remainder of the examination, incuding genital examinaton, s nomal. aboatoy studies:
Folicle-stimulaing hormone uteinizing hormone Prolactin Morning testosterone total Conrmaoy morning testoserone (otal Thyroidstimuating hormone
12 mU/ 2 /L ) 10 mU/L 10 U/L Normal 148 ng/dL (5.1 no/L 37 ng/dL (4. nmol/L Normal
A pituitary MRI s normal Bee initiating therapy this patient which o the lowing should be detemined?
A B (C (D )
Bone minera density Desie r fertlity Fasing plasma glucose eve Scrota utrasound
Item 33
- n alu u -ee l . l ' ' : l v uq <
C
Self-Assessment Test
C a G CONT.
wh dy z: he day h ch c ha O ° (00 7/ 11 e / 0/ " w j [ uy h d- y Laboratory stdies:
y c d- hy )
0 00µ X 0'/ ) <000 µ/ (000 ) 7 /_ 7 )
Which of the lowing i the most ikely diagoss?
() () ) )
E c P hy ·
Item 34
A 39-year-old man is seen r a follow-up examinaion. hree months ago he underwent an organ-sparng pro cedure r squamous cel carcinoma of the throat As part of his sugery his thyoid and all u paathyroid glands were removed. He was started on 1,25-dihdroxyvitamin D (calcitriol) and supplemental calcium carbonate lowing surgey. He subsequently competed a course of concu rent cisplatinbased chemotheapy and radiation therapy without signcant compications and currently eels well with no new signs or symptoms. Medica hstoy is oth erwse unremarkable except fr a 25-pack-year smoking history; he discontinued obacco use a he time o diag noss. Medications are calciriol calcium carbonate and evothyroxne On physical examination temperature is 37. °C (98.6 °F), bood pressure is 125/84 mm Hg, puse rae is 85/min and respiration rate is 12/mn. BM! is 2. Well-healed surgical incisions are noted on he anterior neck e remander o the examination s unemarkable. Lortory tue
Cacium Creatinine 1,25Dihydroxyvtamin D -ou ine lium
85 mg/dL (2 mmoL) 8 mg/dL (7.7 mo/L) Wthin therapeutic range 7 m/ (. mmol/ h)
hih of the llog he ot pproprate gemet of th pte' poturgl liu therpy
(A) Check 25-hydroxyvitamin D level (B) Check parathyroid hormone level
(C) Coninue current treatment regimen (D) Decrease calcium supplemenation tem 35
A 4-year-old man wth tpe 1 diabetes meltus presents to the oce. He seeks advce on his diabees management as he ntensies his exercise rotne in prepaaion r partc ipation in a 1-K race. He reports prolonged hypoglycemia durng ntense exercise, despte eating a meal prior to the activiy. His insuin egien i s insulin gargne and insulin gluisine. Hs most recent hemogobin A level was 7.%. hh of the owig i the ot pproprte gee of thi ptet' hypoglyea o the y ht he exee
(A) Decrease meal-ime insuin glulisine dose prior to exercise, continue nsuln glagine dose (B) Discontinue insulin glargne contnue nsuln glulis ine dose (C) Increase meal-tme protein prio o exercise, continue current insulin doses (D) Swich insuln guisine to a sliding-scale regimen, coninue nsuln glargine dose em 6
A 54-year-od man s evauaed because of tigue He aso notes constipaton and cold ntoerance Medica story is signicant r tonsilar squamous cel cacnoma treated with raiation 3 years ago. here s no mily hsto of thyroid disorders. On phsical examinaton, the skn is dy Mld per obita edema is presen e thyroid s of norma sie and wthout nodules. Reexes are delayed. Laboratory sudies show a hemogobin eve of g/dL 11 g/L), a serm sodum evel o 129 mq/L (129 mmol/L), and a serum thyroid-stimulatng hormone (TSH) eve of 1.4 µU/mL (1.4 mU/L). Whh of the llog the o pproprite ext ep geet
(A) (B) (C) (D)
Free thyroxine (T measurement Repeat TSH easuremen in 4 weeks hyroid scintigraphy hyroid ultrasound
em 7
A 24-year-od woman is evaluated hypercalcemia nci dentay discovered on aboraory studies perrmed r another ndication. She reports o hypercalcemiarelated symptoms. Medical histoy is signicant fr gastoesopha geal relux disease and menstual migraine. Famiy hisory s oale or a rote wo as a calcium polem. ei cations ae omepraole and sumatriptan as needed. On physical eanaon empeatue s 36.2 °C (97. °F) blood pressure is 17/68 mm Hg, pulse rate is 73/min, and respiraion rate s 1/min. BM! is . Chest, hear, and abdominal examnatons are norma as is the remainder of her examnation 83
Self-Assessment Test
Laboratory studies are sgnicant r a serum calcium evel of .2 mg/dL (2.8 mmol!L), parathyroid hormone level of 55 pg/mL (55 ng/L) ad 25-hydroxyitamin D level of 35 g/mL (874 mol!L). Kidney and thyroid uctio studes are orma.
Whch of the lowng is the most approprate next step n managemen? (A) (B) (C) (D)
Bone densitometry Measuremet of urine cacium ad creatinine levels Parathyroid sestamibi scan Refrral r parathyroidectomy
oo owg ow-do oigh o o Sb g oooi hoo . A ot CT web 7- gh a o o o g 0
Which o he owig s he mot appopiae peioperaive maagement A ) C)
oop hooo oop ot oope op o o
Item 38
A 25-year-old woman wth type 1 diabetes mellitus is eval uated r recet-oset glycemic luctuations without symp tomatic hypoglycemia She was diagosed with diabetes 7 years ago. Her hemoglobin A1 levels sice diagoss have ranged rom 64% to 7.3% with the most recent value at 7.3%. She reports eating a carbohydrate-consistent diet a each meal wh little varation her selection of meals or sacks. She started a new job severa moths ago but continues her daly exercise routie a d sleep schedule. She has no othr medicl probems or symptoms Her diabetes treatment regime is insuli glargie on ce daily ad insuln lispro three times daily. Physical examiation ndings and vita signs are nor mal. Estimate glomerular ltration rate serum creatiine level nd urie albumi-creatiie ratio are normal. Her blood glucose values rom the previous week are show beow c
Blood gucose values: Lunch Breakast (mg/dL (mg/dL mmo/L) [mmol!L]) 24 (69) 0 (6.) 5 (6.4) 7 (65) 08 (6.0) 0 (5.6) 26 (7.0)
90 (0.5) 9 (5.) 8 (6.5) 7 (7.0) 0 (5.6) (6.2) 87 (0.4)
Dinner (mg/dL mmolL])
Bedtme (mg/dL molL)
09 (6.) 2 (62) 2 (6.2) 204 (.3) 22 (6.8) 06 (5.9) 02 (5.7)
20 (.6) 26 (7.0) 26 (7.0) 0 (6) 4 (63) 72 (4.0) 96 (0.9)
Item 40
A 62-year-od man is evauated r right leg pai. he pa has developed progressively over the past 6 months and worses with prolonged activity such as playing golf Med ica history is unremarkable and he takes o medications On physica examnation temperature is 36.3 °C (97.3 F) blood pressure is 28/67 mm Hg pulse rate s 73/min and respiraton rate is 0/mi. BM is 29 here is o pain to palpatio over the femora region ad he has normal rage of motio. Laboratory studies are sgnicant r a serum akaie phosphatase leve of 200 U/L ad serum calcium eve of 90 mg/dL (2.3 mmol!L). Plai radiograph of the right femur is shown
Whch of he owing s he mos key cause of the luctuatng glycemc conrol? (A) (B) (D)
Antibodies to exogenous isuin Gastroparesis Iq appropriate isuln timng
Item 39
Which of the owng s the most appopate next step in managemen?
o o g ot o hto. gh g gz s. g boro aio dos oo o o o
(A) (B) (C) (D)
C A 0-o o d o h ot f
84
Atiresorptive therapy Boe biopsy Evaluation fr mutipe myeoma Ciica observation
Self-Assessment Test
Item 41
Item 43
A 29-year-old woma is evaluated during her s prenaal visit She fees wel edical history is signica only hypothyroidism, r whch she has take levothyoxne, 100 µg/d r the last years. Her oly other medication s a preatal vitamin. O physical examinatio she s afebrile. Blood pres sure is 98/72 mm Hg puse rate is 88/min, and espiration rate is 2/min. he thyroid is of normal sze and wthout odules ere s o cervical ymhadeopahy Cardio vascular ad ulmoary examiatios ae uremarkale. Abdomial examinatio reveas orma bowel sounds he uterus is not palpable. Laboratoy studies show a serum thyroidsiulang hormoe evel of .6 µU/mL (.6 mU/) ad a serum toal thyoxie (T ) level of 45 µg/dL 58 nmol/L)
A 44-year-od woman is evauated fr weght gai muscle weakness, and metaboic sydrome She has hirsutism but also notes hair loss on her head. She has bee ameorrheic r 2 years. edical histoy is signicat r hyperlipdemia type 2 dabees meltus hyertension ad obesiy. Medications are aovastatin, memin, and isinopri. On physical examiaon blood pressue is 156/92 mm Hg ad pulse rate is 78/mi B! is 42. She has a cushingoid apeaance ace, ad moderate hirsutsm aectig the chi upper lp beasts, ac ad chest ere ae several wide vio aceous strae across the adome and he back o her arms.
4
Which of the owing is the most appoprate eatme nt o hs paen's hypohy oidsm?
A) (B) (C) (D)
Coninue levothyroxie dose Decease levothyroxne dose Discontinue levothyroxie cease levothyoxie dose
Laboraoy studes
Adenocorticotropic hormoe (ACTH) Corsol 8 afte 1 mg o dexamehasoe the ight bere 24- Hour urine cortiso excretion ital measuement Repeat measuremet
52 pg/mL (114 pmol/L) 5.2 µg/dL (14.5 nmol/L)
124 µg/24 h (41.7 nmol/24 h) 98 µg/24 h (2700 mol/24 h)
ltapetrosal sius samplig denties a pituitary micoadenoma as the source o the high ACTH level Item 42
A 6yerod m i evlued in e oi eve ou o nuse igdede nd d don a e uderwe uolied eil orc vve replaeen 3 days ao e had ee do wel posop eaivey ui e developmen o hi en sypo edil history sna oly r ypoyrodis Med iction re hepeui unactioned heri levoy oe. nd asneeded oycodone O pyl eanon ee s 7 C (990 °F bood resse 80/0 use e 0/in ad reio ae i 8/ BMI i 6 Emion o e che ows len d dy s woud Crdac einion reve eul acyr di ad echanc S ee i no w aio o he adoe o loe ck ige aion i noa Laboraoy sudies:
eogoin Leuoyte coun Acived l obopsin ie Creinine Sodiu ou Corio do
73 g/ 73 g/ 90 /d 90 / pooeivel 000/ 0'/ 70 0 g/d 88 o/ 30 q/ 30 ol/) 60 q/ (60 o/ < d o/
Whch o he owng s the most appopriate test to per rm next?
A 8-mg dexamethasone suppressio est B) 2-ou urie free catechoamine ad metaephrine easuremet (C Dualeergy x-ray absorptioery scan (D) PTsca tem 44
8-yod wo i eig dsrged o the oal i dnos o uoiune drenais Medc isoy i orwe unerkle d she ws on o edicos rio o dso On hyial enaion eerure is 370 °C (986 F ood eure i 0/80 g pule re i 80/in nd eron ae i /in MI s Icreased kin pgme on i oed over he eeno ue o e etree ieraly e reder o" r einion oa Wich o e owing is he mos approp riate ong -tem medicaion regmen th is paient
A B C
eeoe once dy Fudooe 00 g oe daiy ydooone g hree ies dily redion mg oe diy nd udocorisoe
Whic o te owing is he mos ikely diagnosis
A J (C (
Auoiune dreni era denl hemorrhae Oiedued adrenl iuiency Piury apopley
Item 45
A 78-year-od woman is evaluaed f a -week hstory of unintentioal weight loss, ight sweats ad eck swellig. She has moe recey also had diculy swallowig solid 85
363
Self-Assessment Test
fods and positiona shortness of breah She does not have hoarseness palpitations or change in bowel habits. Prior to he development o these symptoms, she had been in her usual stae of health wit h no illnesses. She has hypothyroid sm and has been akng levothyroxine r 40 years wth a stabe dose r he pas 10 years On physcal examation temperaure is 36.9 ° (98.4 °F), bood pressre s 40/88 mm Hg, puse rate is 75/min, and respiration rae is 12/min. e thyroid is symmerically enlarged, rm, and xed. ere is no thyroid bri. CT scan of the neck is shown
Wc of te llowng is te most appropriate management of tis patient?
(A) (B) (C) (D) (E)
Refer r parahyroidectomy Start alendronate Start cactonin Start cinacalcet Sart vtamn D3 cholecalcferol)
Item 47
yr-ol n s ated o he os r evion ' n ch pan hstoy s n o y 2 t e coonay ay s, hye tnon n yeriidea a s bs as oe h d xr . ohr on spn etooo aovstt b iroyern s eeed s ni a o vl r 0 o 20 /L (94 o ess o o oraoy ti norm Wic of te llowing s te most appopate teatmet ts atiet's abetes we osptaze?
() () () )
r nu z t ga in
tem 48
Whic of te lowing is te most likely dagnoss?
(A) (B) (C) D)
Graves disease Papllary thyroid cancer Primary hyrod lymphoma Sbacute thyroidtis
Item 46
A 6-yearold man is evaated r a recent diagnosis of primary hyperparathyroidism afer an eevated serum cal cim leve was incidentally deteced on aboratory testing Medcal history is sgnicant only r hypertension, and his only medcaton is rampril. On physical examinaton emperatre is 35.8 °C (96.4 °F), blood pressure is 120/68 mm Hg, plse rae s 62/in and respiration rate is 14/in. BM! is 32. e remainder of his examinaton is unremarkabe Laboratory studes: Calcim Creatnine aratyrod hormone 25Hydroxyviamin D Estmaed gomerular ltration rate
0.9 mg/dL 27 mmolL) 0 9 mg/dL (79.6 µmo/L) pg/m ( ng/) 9 ng/mL (7 nmolL) >60 mLmin/1.73 m2
A dualenergy x-ray absorptometry DEXA) scan shows T-scores of 1.3 in the right emora neck, 1.0 in the lumbar spine and 1.4 n the nondomnant rearm Frac tre Risk Assessment Tool (FRAX) score indcates a 13% risk o major osteoporoic fractre and a 1 .9% rsk o hp acure over he next 10 years 86
A 43-yarold woman is evauatd r progressiv wight gan over the past 2 years. Her previos weig h was 2.6 kg (160 lb) b has steadiy risen to he curren weight of 106.6 kg (235 lb). She notes a sligh increase in her appetite bt minimal change in her ifestyle or activity leve She has ried to ose weight wth increased exercise and ntrtional counseling but without signcant rests. More recently she repors having tro uble sleeping and decreased exercse tolerance wth activtes such as walkng up steps Medcal history is signicant r impaired fsting glucose hyper tension, and hyperlipidemia. Medicaions are hydrochlo rothiaide and atorvastatn. She has not been prescribed glucocoricoids or had glucocortcoid joint injections On physical examination temperatre is37.2 °C (990 °F), blood pressur is 136/86 mm Hg, pse rate is 88/min, and respiration rate s 12/min BM! is 38. She has rounded cies, thin hair mild hirsutism, and prominent t deposition in the dorsocervical and spraclaviclar areas. Hr skin i s thn, and she bruses easily, although sriae are no t presen. Her examnation is oherwse nremarkable. aboratory stdies are signicant r a fsting plasma g mg/ ( mm/) an nm y roidstimlating hormone level ic of te llowing is te most appropriate next step in evaluation?
(A) () (C) (D) (E)
Adrenocortcotropic hormone measremen 1-mg dexamethasone sppression test 8mg dexaehasone supprssion tst Pititary MRI Serm corisol measrement
C
Self-Assessment Test
Item 49
tem 51
A SO-year-old man undegoes follow-up evalua tion for type 2 diabetes mellitus. His daily log demon strates aveage bood glucose evels of 120 t o 150 mg/dL (6.78.3 mmolL, with hypoglycemia in the 50 mg/ dL (2.8 mmol/L ) range noted once o twice per week wthout a discernible pattern. He s unable to deect the hypoglycemia The patient has a medical hstoy of dabetc ret inopahy chronc kidney dsease peripheal neuop athy, hypertension hypelipidema, obstructive seep apnea on bilevel positive airway pressue ) gastro esophagea reflux disease and oseoathrtis in both knees He repots ntoerance o stenuous exercise due to knee pain. He s able to walk 15 minutes daly He has worked closely with a nuttionist resuling in a 0 kg 11-lb weight loss over 1 year whch has plateaued recently. Medicaions ae insulin glargine, insulin aspart lis inopri cavedilol pantopazole, aspirn, and atovas atin n physcal examination bood pressure is 140/ 90 mm Hg and puse rae is 65/min B! s 37 Bilateral proliferative retinopathy s present ere are no carotid buits or cardiac murmurs Bilatera oss of monolament and vibratoy sensation on the feet and decreased ankle relexes are noted. he remainder of the examnation is norma Resuls of aboratory studies show hemoglobn A1 level of 8.2% and serum creatinne level of 17 mg/dL (150.3 µmol/L
A 64-yea-od man with type 2 diabetes melitus and sage 4 chonic kidney disease is evaluated r continued glycemc management He s llowed closely by the nephology ser vice in prepaaon r impending hemodialysis with initi ation o erythropoietin herapy within he last 3 months His average sting and preprandia blood gucose values are in the 145 to 190 mg/dL (80-10.5 mmol/L range He does not have hypoglycemia. His insulin regimen conssts of nsulin detemir at bedtme and insuln glulsine bere meals His most ecent hemoglobin A 1 value has deceased om 7.5% to 6.2%
e
Which of the lowing is the mos appopriate teatment of his patient?
(A (B (C) (D
Bariatic surgery Increase insuin Initate mermin Initate pamlintide
Item 50
A 47-year-old woman is evaluated r an incdenaly ds covered right adrenal mass n physical examination blood pessure is 120/80 mm Hg in both arms and pulse rate is 84min he abdomen s nontender and here are no papable masses he remain de of the examnation is unremarkable Noncontrast CT of the abdomen demonsrates a 3.2-cm well-cicumscribed, partialy cystic ight adrenal leson wih a density of 30 Hounseld units. A owdose dexa mehasone suppression test is negaive r evdence of cor tisol hypesecretion.
Whch of the lowing is the most appopriate management his paient's diabetes?
(A (B (C) (D
Coninue curren heapy Decease insuln detemi dose Discontnue preprandial nsuln glulsine Measue postpranda glucose level
tem 52
A 34yeaold woman is evaluated hirsutism and acne that began 4 months ago he aso eports that her voice has become deeper Her menstrual perods have emained regula occurring evey 28 days he has one son 5 yeas of age. he epors that her pregnancy was uncomplicated and she had no diculty conceiving he had a tubal ligation fllowing the brth of her child he has a sister with polycystic ovay syndome. he akes no medcations n physical examination, blood pessure is 140/84 mm Hg and pulse rate is 62/min BM! is 21 he has hyperpig mented erminal hais on the chin neck abdomen and lower back and comedones and pustues on he face and upper back here s ontotempoal hair loss he remain der of he examnation is unremarkable. Laboaory studies:
Cortsol fee urine Dehydroepiandrosteone sule Proactin Testosterone
26 µg/24 h 716 nmol/24 h 82 µg/mL (221 µmol/L ) 8 ng/mL 8 µg/ 96 ng/dL (33 nmol/L )
Which of the llowing is the most appropiae diagnostic est to pem next?
(A B C D)
Abdomina CT scan Low-dose dexamehasone suppression test Pevic ultrasound Pituiay MRI
Wich of the llowing is the mos appropiae next sep in managemen
Item 53
(A (B (C D (E
A 27-year-od woman is evauated management o he ype 1 diabees mellitus. he was dagnosed 10 yeas ago he has no known complications om her diabetes he eats a healthy diet and exercses an average o 60 minutes per day in the evening he takes nsulin glagine and insulin aspa. he is adheent wih her insuln egimen and checks he blood
Adenalecomy CT-guided ranscutaneous biopsy Plasma aldosterone to plasma renin atio Plasma free meanephrnes No additonal testing is indicated
87
Self-Assessment Self-Assessm ent Test
gucose level three to ve times pe day. Her average bood gucose vaue is 125 mg/dL (69 (6 9 mmo/L), with sting gucose vaues rangng om 80 to 150 mg/dL (44-83 mmo/L) She rouiney measures her 2-hour postpranda gucose vaues and hey are consistenty less than 150 mg/dL (83 mmol/L) She has sevea overnigh blood glucose values anging fom 90 to 140 mg/dL (5078 molL) Her hemoglobin A c vaues ove he last 6 onhs have been 73% o 75% She is dscour aged that he hemogobin A values rema above 0% Laboratory studies incuding creainne and compee bood count are normal 1
c
Wih of the lowing s he most appoprae managemen of her her elevated hemoglob A1 evel?
(A) (B) (C) (D)
Begn coninuous glucose glucose moniong Increase exercse Increase insuin aspat Increase insuin glagine
Item 54
A 25yearod woman s evaluated aer a recen diagnosis o poycystc ovay syndrome She is conceed about hisut ism and rregular menses She has no desie to be pregnant a his ime She takes no medcaions On physica examinaton she s aebrile Bood pres sue s 10/60 mm Hg puse ae is 68/min and esprat ion rate is 16/mn; BM! is 37 Coase hair s noted on the chin jawne and periumbcal periumb cal area. he emande of her phys ca examination incudng pevc examnaton is nomal Wh of the owng is he most approprae appropr ae eament?
(A) (B) (C) (D)
Combined oral contraceptive pis Intermien pogesin wihdrawal Levonorgestrel Levonorges trel intrauterine system Spronoactone herap herapyy
erectons but epots ow libdo and occasiona erece dys unction durng intecourse He wakes once durng the ngh to uinate and drin water He esmates hat he uinates 5 to 8 times during the day which is unchanged Medica history s sgncan f tanssphenoida esecion o a craniophayngioma at age 18 years He has equired antero ptuitary horone epacement and des mopressn mopress n snce ha ime Medicatons are desmopressin hydrocorisone evothyroxine somatopin and testoster one enanthae On physica examnaton temperatue s 370 °C (986 ( 986 F) bood pressure is 118/64 mm Hg puse ate is 74/mn and espration rate s 14/min No orthostatic changes ae noted BM! is 24 ere are no cia changes suggestive o acromeg ay or Cushng syndome he hyrod s normal without goter or nodues Hair distibution and skin urgor ae norma ere s no gynecoastia or stae Norma penis and estcuar voume are noed Visua eds are intact on neurologic examinat examination ion Laboraory studies: Sodium 138 mEq/L (138 mmoL) nsunie gowh ctor 1 orma oactin 18 ng/m (18 µg/L) yrod-stimuatng hormone 08 µU/mL (08 /) hyroxne ( ee 07 ng/dL (90 pmo) estoserone (11 days ate 482 ng/dL (67 nmolL) njecon) ollow-up MR!s show no resdual umo Wh o he lowng is the mos appropriae management?
(A) (B) (C) (D) ()
Increase desmopessin Incease hydrocorisone Incease evothyoxine ncrease esosterone enanthate Stop somaropin
Item 55
Item 57
A 46year-old man s evauaed owing a diagnosis ofpheo of pheo chromocyoma e has no signs or symptoms at this ime Except r hypertenson his medcal hisoy is unremark abe Medcaions are isinop and hydochorothazide On physca examination bood pessue s 10/90 mm g and puse ate s 90/ 90 /mn he emainder of the physca examinaon is unevealng.
55-yea-od man is evauated owng a sceenng r type 2 diabetes melitus He is asymptomatc He has a his tory of hypetension and hypeipdemia ere is no history of anemia, iver dsease or kdney disease Medcatons are isnopri and rosuvastatin On physcal examination bood pressure s 123/ 76 mm g and puse rate is 2/min BM! is 28 he remainder of he examination s unemaable Laboratory studes Hematocrit 456 reatinine 10 mg/dL (884 mol) Gucose fasting 128 mg/d (7 mmo) emogobn A 5.6%
Whh of the the lowng s the most appoprate ne sep in managemen?
(A) (B) (C) (D)
Increase isinop isinop dosae Pem contrastenhanc contrastenhanced ed adrena CT can Stat phenoxybenam phenoxybenamne ne Sart popranool
Item 56
A 38-yea 38-yeaod od man wth panhypoptuitarsm panhypoptuitarsm s evauated evau ated worsening worseni ng tgue and weght gain over he past 3 months He s seeping 9 hours each night but he fees ired during he day and has decreased s usua exercse eve He has morning 88
Whh o he llowng s he most approprae dagnos est to perrm nex?
(A) () (C) (D)
Fastng pasma gucose Heogobin A Oal glucose toleance test Random bood glucose
Self-Assessment Self-Assessme nt Test
Item 58
A 34-year-old man is evaluated r a 2-year hstory of tgue, lo w libdo, and nfertlty. Hs mly hstory is nota ble fr a brother wth nfertl nfertlty. ty. Hs medcal hstoy s unre markable, and he takes no medication medications s On physcal examnation vtal signs are nomal. Hs height s 1956 cm (77 n) and hs weght s 86.2 kg (190 lb) Gental examnation reveals small, rm testes blateraly. Laboratory studes reveal a mong serum total tes tosterone level of 140 ng/d (4.9 nmol/} (whch was con rmed on repeat testing), a serum s erum fllcle-stmulatng hor mone evel of 24 mU/m (24 U/L}, and a serum utenzng hormonee eve of 18 mUm (18 U/L} Repeated semen hormon semen ana yses reveal aoospemia hich of the lowing is the most appropriate diagnostic test to perrm next?
(A) (B) (C) (D)
Kayotype MRI o the ptutary Scrota ultrasound Serum prolactn measurement
Item 59
An 84-year-old man s evaluated moderate tigue. He otherwse feels wel and does not have constpation cold intolerance weght gan or loss anxety tremo palpita tons, or dyspnea. Medca hstory is sgncant r hyper tenson, and hs only medicaton s feodpne On physcal examnaton, he s alert and orented. Blood pressure s 144/83 mm Hg; other vta sgns ae normal. he thyrod is not palpable Cadopulmonary examinaton s normal. Iere s no perphera perphera edema Neurologc examna ton s noncal and deep tendon reexes are normal Laboratory Laborator y studies:
Complete blood count Comprehensve metabolc prole yod-stmulatng yod-stmulat ng homone (TSH) Free thyroxine (T
Normal Normal 6.4 µU/mL (64 mU/} 13 ng/dL (16.8 pmol/L}
Wich of the owing is the most appropriate management?
(A) evothyoxne therapy (B) Measurement of serum total trodothyonne trodothyonne (T3) leve (C) Measurement of serum total T leve (D) Repeat TSH and free T measurement n 6 to 12 weeks 4
Item 60
A 62-year-old woman s evaluated r an ncdentaly ds covered eft adrena mass. Two weeks ago the patient was evaluated evaluat ed in the emergency department r duse abdom nal pain and vomtng. A CT scan was obtaned that was normal except fr the adrenal mass. Iee hous after pre sentaton to the emergency department the pan resoved spontaneously.
Her medcal hstory s sgnicant r det-controlled type 2 diabetes meltus dagnosed year ago and oste opoross dagnosed 4 years ago. Her only medcaton s alendronate. On physical examinaton tempeate s 37.0 °C (98.6 F}, blood pressure is 120/80 mm Hg, and pulse rate s 70/mn. BM! s 26 e emander o the physcal examnation is normal. aboratory evaluaton eveals a serum sodum eve of 139 mEq/L (139 mmol} and serum potassum level of 4.1 mEq/ (4.1 mmol/} e prevousy obtaned CT scan shows a 20cm wel-crcumscibed left adenal leson wth a density of Hounseld units In addition to screening tests r pheochromocytoma, which of the owing is the most appropriate diagnostic test to perrm net?
(A) Adrenal ven sampng (B) Lowdose dexaethasone suppresson test (C) Plasma renn renn actvty and aldosteone concentraton measureentt measureen () No uther testng Item 61
A 68-year-old man s seen n low-up r a ecent e cent dagno ss of acromegaly. He pesented wth chonc ftigue joint and back pan and an ncrease n hs shoe se over the past 2 years Medcal hstoy s sgncant r hypetension and type 2 dabetes melltus Current medcatons are lsnopril, etrmin and as-needed aetamnophen. On physcal examnaton blood pressure is 146/88 mm Hg and pulse rate s 90/mn. BM s 29. He has a promnent bow Macoglossa s present. Lung and heart examnatons are unremakable. Musculoskeletal examnaton reveals age hands and knees with bone swelng and crepitus Skin s thckened and there s excessve perspraton On neuroogc examinaton btemporal hemanopsa s noted. Laboratory studes are sgnicant an elevated serum nsulnke gowth ctor 1 level of 996 ng/mL (996 µg/} and serum prolacin leve of 4 ng/L (42 µg/L} MRI shows a 1.8-cm puitary macroadenoma that eevates the optc chiasm and appears to envelop the left carotd artery and nvade the left caveous snus Ie optc chiasm is midly atrophed Which of the owing is the most appropriate next step in therapy r this patient?
(A) (B) (C) (D) (E)
Dopamine agonst Gowth hormone eceptor blockade Somatostatin analogue Stereotactc radation therapy Tanssphenoda pitutary surgey
Item 62
A 47-year-od man s evaluated postopeatvely llowng thyrodectomy r paplary thyrod cancer. Preoperatve evaluaton showed no evdence of dstant metastatc dis ease, and he underwent total thyrodectomy wh cental 89
Self-Assessment Test
and le ateal neck dissections. The patent's medical is tory is otewise unemakabe On pysical examination, vital signs ae nomal. Te neck sugical sites ae cean and dy Te emande of te examination s unemakable The sugical patology eport eveals a 35-cm papilary tyoid cance in te left lobe of te tyroid and six maig nant lymp nodes out of 35 dissected Tere s evdence of minor extatyoidal extension and vascula invasion by te pimay tumo Which of the llowig is the most appropriate postopeative teatment?
(A) (B) (C) (D)
Doxoubicin cemoteapy Extenalbeam adoteapy Radoactve iodine teapy No additona teapy
Item 63
A 66yeaold man is evaluated n te oce afte being teated in te emergency department r an exacebation of cronic obstructive pumonary disease. Wle n te eme gency depatment e was noted to ave a random bood glucose level of 211 mg/dL (117 mmolL). His emogobn A was 78% at te time A epeat andom ngestick blood glucose level in oce is 204 mg/ mg /dL (1.3 mmol mmolL). he patient eports ecent polyuia and polydipsia. He as lost 6 kg (132 b) over te last 3 monts He a s cronic cronic epigastrc pan assocated wt loose oily stools due to conc panceattis He as a 20packyear istoy of tobacco use and po acool use oweve e does not cuently use aco o. Cuent medicatons ae enteiccoated panceatic enzymes vitamins totopium inaler, and an albuteol inale as needed. On pysical pysical examination, tempeature tempeature is 37.1 °C (988 ( 988 °F) ° F) blood pessue is 3075 mm Hg and pulse ate is 90/min BM! s 22 He H e as mild epigastic pain on palpaton witout ebound tendeess o guading Te rest o f is examination is unemakable Wich of the llowing is the most appopriate treatment hs diabetes?
xenatde (B) Glpzide (C) Insulin (D) Met Metfm fmn n
Which of the llowng s the most appropiate teatment?
(A) (B) (C) (D)
Clomipene citate In vto fetilzaton njectable gonadotopin Metmin
Item 65
A 64yeaod woman is seen f llowup evaluation wo weeks ago se was in a ca accident and an incidental ptu itay adenoma was fund on a cevical spine C scan Se as no esdual injuies om te ca accident. Se is oterwise ealty and takes no medicatons Se went toug menopause at age 5 Se as ngt sweats two to tee tmes pe mont and occasonal ot uses. hese ave impoved over te past decade and ae not botesome Se is not sexually actve Se as neve taken omone eplacement teapy Se as ad no cange in vsion, eadaces o galactorea. On pysca examinaton temperatue is 375 °C (995 °) bood pessue is 110/63 mm Hg puse ate is 82/min and espiration ate is 4/ 4 /mn BM is 26 ee is axilary and pubic air loss Visual elds ae intact Tee ae no ndngs suggestve o f Cusng sydrome o acomegaly. Laboatoy studies:
strado olclestimulating omone Luteinizng omone Prolacti yodstimuatingg omone yodstimuatin yoxne ( fee
<20 pg/mL (34 pmolL) 64 mUmL (64 U/) 32 mU/m (3.2 U/L) 53 ng/mL (53 µg/L) 32 µUmL (3.2 mU/L) 11 ng/dL (142 (14 2 pmolL)
ituitay MRI sows a mm adenoma in te anteior sela. e tumo is not invasive. It does not appoximate te optic casm he ptuitay stak is mdline. Wch of the owing is the most appopriate manage ment?
(A) (B) (C) (D)
Begn dopamne agonist Gamma knife stereotactic radiosugery Repeat testing in 12 monts monts anspenoda anspeno da resection
(A)
Item 64
A 34yeaod woman is evaluated because se and e male patner ave been tying to conceve 13 monts witout success Her medica istory is notable r a 6yea istoy of irregua menses and a ecent diagnosis of poycystc ovay syndome. He only medication is a penata vitamn On pyscal examinaton vital signs ae normal BM! is 36. erminal air growt on te cn uppe lip and sides of te ce is noted No evdence of abdominal or pevc masses clitoromegaly o galactoea is detected 90
tem 66
A 5yeaold man wit a 5yea istoy of type 2 diabe tes mellitus s evaluated r bilateal buing sensation in is feet for te ast 6 to 12 monts The sensation wosens a ngt mogobn v av man tan 70% te ast 2 yeas but wee betwee 80% and 9.0% bee impementing signcant lifestyle canges and tansitioning to insulin teapy fom metfmn te apy 2 yeas ago His medical isto istoy y includes coonary atey disease disease stdegee atioventicula block nonpoiferatve dia betic retnopaty ypetenson and ypelpidemia Medications are egua nsulin neuta protamine Hagedon (NPH) insuln aspiin metopolol atovastatin and lsinopril 1
c
Self-Assessment Test
On physical examnation ndngs are compatble with distal poyneuropathy Which of the lowing is the most appopriate management of ts patients neuopathy?
(A) (B) (C) (D)
Amitriptyline Duloxetine Nerve conduction study Vitamin B measurement 12
C A 72ye e h eey d Item 67
veg. H w e h e w het ees h n blod ve ee by mcy a ve w / ( / w ve g e ' v e whh h d g ev 85 /l (47 /L H y e th h d e n v uco Wh egey de h w vid o v h ee ve 8 / (4 /) w en. Te en · we el e v dh v he l ev we r h de w ay 7 hr y e H e y yere oe Md e bu y h d e Bl / u r 8 MI . e y r r by pe eb p n A e hyye ee o n l rl d �ydryye eve Wch of he llowng s e mos appopae diagn ostc saeg r this paien?
(A) Hylye w () - h yy e sy yy () lu le w hyly a h e yp yye (D) 7H wt ygy h yc hyyce tem 68
A 2-year-old woman is evaluaed r a 3-mont history f amenorrhea accompaned by cyclic pelvic pan. Preceding the onset of amenorrhea she ad a reent diaain a curettage to remove retained products o conception aer a rsttrmester spontaneous aborion er ersonal and fmiy medca history is unremarkable. She takes no med icatons On phyical examination, she is afebrile Bood pres sure is 110/60 mm g, pulse rate is 68/min and respiraton
rate s 6/mn. BM! i 24 elvc examination reveals a non tender moble uterus. Laboraory studies:
Estradiol Follcle-stimuating ormone Luenizing hormone Prlacin yroidstimuating hormone Ure human choronic gdotrop
<80 pg/mL (2936 pmol/L) 62 mU/mL (6.2 U/L) 4. m/mL (4.1 U/L) Normal Normal Negatve
Whch of he llowing is he most appopriae diagnostic es to perm next?
(A) (B) (C) (D)
MR of he ptuitary Pepheral karytype Progestn wthdrawal test ransvagnal ultrasond
Item 69
A 29-yearod woman comes to the oce fr a llow-up evalation She was diagnosed with type 2 diabetes mellitus 2 yeas ago. Her sting and premea blood glucose vaues range rom 120 to 150 mgdL (6.7-83 mmol/L) She has had o hypoglycemc events She has been adherent with her insuin regmen along with det and exercise modcations er hemoglobin A leve has decreased om 9.0% to 7.% over the last 2 months. She expresses fustration over the need r multple medicatons to treat her diabetes Medical histor s othewise nremarkable. Medcations are insulin glargine, nsuln aspart, and metrmin On physcal examnaton blood pressure is 120/72 mm g and pulse rate 80/min. BM is 27 e remainder o the examnation is norma. Hemoglobin A evel s currently 7.4%. Results of all other labratory stuies are normal Whch of the llowing is the most appropriate managemen of ths patien's diabees?
(A) (B) (C) (D)
Icreae insulin glargine dose Measure 3 blood glucose level Measure postprandia blood glucose eves Swtch metrmin to sitaglitin
tem 70
A 32yearold woman is evaluated r a 2-week hisor o egn body senation in her eyes. Despite ushing the eyes numerous ties wth saline, the sensation remains She also feels pressure behind her eyes. She is not pregnant. Medical htor s nremarkable. On hysical examination scleral injection and peri orba edea are present bilaeraly rigt worse han le Diploia is noted n latera gae ere is no lid lag or proptosis. e thyrid is dusely enlarged and a bruit is noted. Neuroogic examination discloses brk reexe and a bilatera hand tremor Laborator studes reveal a serum thyroid-timulatng hormone level of less than 0.008 µU/mL (0.008 mU/L) a 91
Self-Assessment Test
serum ee thyroxine (T) level of 4.5 ng/dL (580 pmol/, and a serum total triodothyronine (T leve o 365 ng/dL (56 nmo/L Whch of the lowing s the most appropriate next step n treatment?
A (B (C (D
Exteal-beam radiotherapy to the orbits Methmazoe Radioactive iodine otal thyroidectomy
Item 71
A 42-year-old man is evauated r resistant hypertension. He was dagnosed with hypertension at age 35 years and reports that his blood pressure has never been wel con troled He is taking his medications as prescribed He does not ave headaches chest pan paptations shortness of breath or symptoms of panc attack He has no history of cardiovascuar disease does not smoke and does not drink acoho Medications are lsinopril, amodpine hydrochlo rothiaide metoprolol an potassium chloride supplemen tation He is not takng any over-the-counter medications On physical examination bood pressure s 50/86 mm Hg an pulse rate is 65/mn BM! is 4 Examnation o the heart is sgnicant r an S1 but no murmurs e remainder o his examnation is unremarkable aboratory studies are signicant r a serum creati nine ev of 0 mg/dL (88.4 µmol /L stng plasma glu cose level o 8 mg/dL 45 mmol/L and serum potassium level o3 mEq/L (32 mmoL Whch of the owng s the most appopate next agnostc step?
(A (B (C (D
Dexamethasone suppression test Pasma aldosterone-plasma renin activity ratio Plasma metanephrines and cateholamines Renal artery Dopper low study
Item 72
A 65yearold man is evaluated because o painess neck swelng and diculty swallowng that has progressvely worsened over the ast year. He does not have hoarseness but he feels as though his voice is not as strong as t was n the past Medica history is signicant r multiple thyroid nodues. Fine-needle aspiration of three o the largest nod ules 5 years ago showed that al nodues were benign on cytologic examination. Medical history is otherwise une markabe and he takes no medications n hyial eamnation vita ign a noma ·e thyroid s diusey enlarged and mobile with swalowing He has cial ushing when raising hs hands above his head as shown (see top o next coumn No cervca lymphadenopathy s noted. Cardovascular and pulmonary examinatons are norma Reexes are nor ma and there s no visible tremor aboratoy studies show a serum thyroid-stimulating hormone SH level of 4.0 µU/m (4.0 m/L hyroid utrasound shows innumerable coaes cent nodules wth no suspicious sonographic eatures. 92
Iere is duse enlargement of the thyroid and the inerior edge of the gland cannot be visualied. CT scan shows substeal extension o the goiter in the let lobe with mild tracheal narrowing and tracheal devation to the right Wch o the lowing is the most approprate t eatment?
(A (B (C (D
Extealbeam radiotherapy Levothyroxine Radioactive iodine Iyroidectomy
tem 73
A 6-year-old woman s evaluated because she and her husband have been trying to conceive r 4 months with out success. Her husband thered a chld n a previous marriage. Her medcal history is notable r pelvic inam matory disease which was diagnosed and successlly treated at age 8 years. Her ony medication is a prenatal vitamin. Physcal examination ndings are unremarkabe Which o the llowng studes s most lkely to be dag nostic?
(A (B (C (D E
Diagnostic aparoscopy Hysterosalpingogram Peripheral karyotype o the patient Semen anaysis o the patent's husband ransvaginal ultrasound assessment o llicle count
tem 74
A 46-year-od man is evauated r a right ateral neck mass. He rst noted the mass while shavng weeks ago. He does not have hoarseness or dcuty swallowing Medcal hs tory is signicant only r hypertension. Hs ony medica tion is hydrochlorothiaide n physical examnation blood pressure is 65 /95 mm Hg pulse rate is 88/min and respiraton rate s /min. ere is a rm -cm mass in the right lateral neck and a mobile -cm right thyrod nodule.
Self-Assessment Test
: Calcium Creatinine hyroid-stmulating hormone
10.5 mg/dL 2.6 mmol 1.8 mg/dL 159.1 µmolL 4.8 µU/mL (4.8 mL
Utrasound o the neck reveal a hypoechoic thyoid nodule with mcrocacications measuring 1.6 cm ere is a 22cm mass with internal calcications in the area of the papable abnormality. Fine-needle aspiration of the thyroid nodule and the latera neck mass reveals medullary thyroid cance. RET testing is postive r a mutation in codon 634. W g g? A 18-luoo-deoxyglucose positron emision tomography scan B) Plasma ractionated metanephrine levels C) Serum parathyoid hormone evel (D otal thyroidectomy and ateral neck dissection
C Item 75
A 55y -o wom v eege eaen e ml u ve ve wek e y t e egly ou an er gy e e y w oe s ye g A e oy g hypeo e ly mc ho. O py eamo m eove Mucu memn ae y Tmeu i 36 °C (97 o u i 0/9 11 g u a /m n reo e / M! 2 ere due ol e plon h e o e e mkl Lboo de e em u ev o 4 Eq/ 4 m e 40 gL 36 m/L e e v 16 mg/ 4.4 µmol/ m v . mg/L (46 mmo/L Cohadoe i ou vou n al ae ted. W g r g A) C ()
Clo Ca oy Zoed id
Item 76
A 60-year-old man s evaluated during a rout ne fllowup examination. He has type 2 diabetes melitus. Review of hs blood glucose log demonsraes fsing blood gucose values anging from 120 to 160 mg/d 67-89 mmolL and variable 2hour postprandia blood glucose vaues
rangng fom 50 to 190 mg/dL (2.8105 mmol/L His over night blood glucose vaue ange om 120 to 140 mg/dL (6.7-78 mmol/L). He is unable to deect hypoglycemia he patent s concerned about hyperglycemia and he desires to reach a hemoglobn A evel of less than 7%. Medcal hisory is sgnicant r diabetic retinopathy periphera neuropathy hypertension, and hyperlpidemia Medcations are neutral potamine agedon NP insulin regular insulin losatan chlorthalidone metrmin rosu vastatin and aspirin On physical examnation bood pressure is 25/82 mm g and pulse rate s 80/min. BM s 24. Retnal examination demonstates nonproliferative retinopa thy. Hs ower extremities have dminished sensaton to a 10-g monoilament and vibration with a 128-Hz tuning k. emoglobin A eve i 72, and the esults of all other laboatory studies ae nomal. W g ' ? A B C) D)
Continue current insulin and metrmin dose Continue curren insuin, increase mermin dose Decrease meal-tme inuln, add pramlintide Decrease meal-tme inuln, continue metrmin
tem 77
A 28year-old woman i evaluated r a 6-month history of inrtility. In order to predct her fertie period, the patient has been using a home urinary luteinizing hormone (L kit. he ki can ideni an LH urge and therere predict ovulation and the opmal time r inercourse. er uri nary LH kit result has been onsisently positve but her pregnancy est reult cosistently negaive. She has been exercising recently in an attempt to lose weight. er med cal histoy is otherwise unremarkabe and she takes no medications On physical examiation vtal igns ae normal. BM is 38. Coarse teminal hairs are noted on the chn, neck, and anteor chest. Pevic examination i normal. Pelvic ultrasound reveals a thickened endometrium nd polycystic-appearing ovaries bilaterally. W g g? (A (B) (C (D)
Hypothyroidim Late-onset congenta adenal hyperplaia Polycystic ovary syndrome Prolactinoma
Item 78
A 72year-old woman is evaluated in ollow-up or oste oporosis Medical history is signicant fr a hip acture 5 year ago sustained ae a md a. vuon at t time incuded a dualenergy x-ray absorptomety (DXA) scan showing a let hip T-score of 2.8 and vertebral score o 2.7 She has been maintained on alendronate therapy snce that tme. Medical history is also signicant for hypetension Medcations are alendronate hydro chorothiazide alcium, and vitamin D. Family hitory 93
Self-Assessment Test
is sgncan for oseopoross n her mother, sster and maernal aunt She has a 35-packyear tobacco use hstory and contnues to smoe. On physcal examination, temperature s 36.9 ° (984 °F) bood pressure s 138/87 mm Hg, pulse rate s 89/min and respration rate is 12/mn. BM! is 28. She has marked thoracic kyphoss and increased central adposy. Laboratory studes show a serum cacium level of 86 mgd (22 mmol/L) and 25hydroxyvtamin D level o 44 ng/mL (098 nmol/L); dney functon sudes are normal Repea DEXA shows a stable bone mneral densty
On physical examnaton, her temperaure s 32 C (990 °F), bood pressure s 118/68 mm Hg pulse rate s 72/min, and respraton rate is 10/mn BM! s 28 Other wse, her physca examnation s unremarkable Laboratory studies: Human choronc gonadotropn Negave Prolactn 68 ng/mL (68 µgL) Iyroidstmulatng hormone 15 µU/m (15 m/L) yroxne (T4), ee 0.82 ng/dL (10.6 pmol/)
Which of the owing is the most appropiate treatment of this patient's osteoporosis?
(A) (B) (C) (D)
(A) (B) (C) (D)
Change o denosumab Change to terparatde Continue alendronate therapy Inate a drug holday
Item 79
A 55yearold man presens r llowup of a recent diag noss o hyperaldosteronsm. Medca and fmy hsory are unremarable. Medcatons are losartan, metoprool amlodpne and chorthadone. On physcal examinaton blood pressure s 150/90 mm Hg and pulse rate s 0/mn Ie rest of the examnaion s unremarkable. Addional studes incude a nonconras CT scan o he abdomen hat shows a 1.2cm homogeneous left adrenal lesion wth a densty o 5 Hounseld units. Adrenal ven sampng ndicates smar raos o aldosterone to cortso bilaeraly Which of the owig is the most appropriate theapy r this patient
(A) (B) (C) (D)
Bilaeral adrenalectomy Dexamehasone Left adrenalectomy Spronolactone
Item 80
A 24yearold woman s evauated or 3 months of galac torrhea worsenng fatgue and malase. She was wel 6 months ago and whout explanaton began eelng tred and ethargc. She has noted milk eang sponta neousy from her breasts. He r menses have been unpre dctabe She a a oml e m months ago bu then her nex cycle was delayed. Her as menstrual period was 6 weeks ago and she had excessve bleedng. She has stopped exercisng and has ganed 3.6 kg (8 lb). She also reports headaches that occur about 2 t o 3 mes per week. She has noted consti pation and breast enderness. She has no libdo which s a sgnfcan change. She took a home pregnancy test whch was negatve She has a hsory o depresson There is no amly hisory o puitary disease. Her only medcation s sertraline for depresson. 94
Which of the owing is the most appopriate management?
Begn cabergolne Begin levothyroxne Hold sertraline and retest Order ptuitary MI
tem 81
A 33yearod man s evaluated fr inferlty As part of hs evaluaton, azoosperma is dented on two sequential semen analyses. His medcal hstory s otherwse notable r chronc snustis. e akes no medcaons On physcal examnaon, vital sgns are normal. BM! s 24. here is no evdence of inguna herna A small ef sded varcocele s present tha emptes when the patien is recumben. Testcles are o normal se. Absence o he vas deferens s noed bateraly. Which o the owing is most likey responsibe r ts patients inertiity?
(A) (B) (C) (D) (E)
Anabolc seroid abuse Cystc bross Klinefeter syndrome Varicocele Y chromosome microdeletons
Item 82
A 22yearold woman s evaluated r ftgue and weght loss over the las 2 months She describes a ack of energy decreased appette, and an unntentonal 36kg (8b) weight oss Over the last week she has experenced nau sea and occasiona vomitng. She notes no other fcal symptoms She has no signcant medcal hsory. Famly history s remarkable r hypothyroidsm n her mother and type 1 diabees meltus n her brother. She takes no me. On physica examnaton temperature is normal blood pressure s 100/68 mm Hg, pulse rate is 90/mn and respration rate s 12/mn. BM! s 19. Hyperpgmentation s pronounced over he knuckles o he hands and elbows bilaeraly. e remainder of he physcal examinaon s unremarable. Laboratory evaluation demonsraes an 8 AM serum cortsol evel o µg/dL (55.2 nmol/L) a serum sodium eve of33 mE/L (133 mmo/L) and a serum poassum eve o 5.8 mE/L (58 mmol/L).
Self-Assessment Test
Which of the owng is the most approprate next step n management?
(A) Cosyntopin stimulation tes (B) Hydrocortisone and udocortsone (C) Plasma adenocoticotopic homone (ACTH) mea suemen (D) Prednisone Item 83
A 21-yea-old woman is evaluated management of type 1 diabetes. She was diagnosed 3 monhs ago afte pesenting to the emegency depatment with diabeic ketoacidosis He hemoglobin A 1e leve at the me o diagnosis was 15.2% She was discharged fom the hospital on a basal and pan dial insuin egimen with mino adjustments equired as an outpatient. He bood glucose log demonstates a ecent change maniesng as equent symptomatic episodes o both sting and postprandial hypoglycemia with bood gu cose evels anging fom to 65 mg/dL (283.6 mmolL}. Medcations ae insuin gagine and insulin aspat. On physical examination, bood pessue is 0/70 mm Hg and puse ate is 70min BM! is 19 he emande o the examinaion is unemakable Hemoglobin A level is 62% Which of the lowig is the most approprate management r ths patent's hypoglycemia?
(A) Decrease nsulin glargine decrease insuln aspart (B) Dase insulin glagine decease insuln aspat add pamlinide
(C) Discontinue insuln glagine change nsulin aspat to a slding-scale regimen (D) Discontinue nsulin glagne disconinue insulin aspat
Item 84
A 34-yea-old man s evaluated o a 1-yea histoy o decreased libido and sevee eectile dysfunction incuding absence o moning eections He and his femae pane would e to conceive. His medical hstory is ohewise unemakabe and he akes no medcatos. On physical examination vital signs ae noma. BM! is 27. Atophc estes are noted bilatealy. Laboratory studies: Follicle-stimulaing hormone Luteinzing homone Prolactin Moning testosterone (toal) yoid-stimulaing hormone
12 mU/mL (1.2 /L} 08 m/mL (0.8 /L} ng/mL ( µg/L} 120 ng/dL (4.2 nmol/L} Normal
MRI o the pituiay reveals a 08-cm anteo pituitay mass consistent wh an adenoma. Whch of the lowing s the most approprate treatment?
(A) (B) (C) (D)
Cabegoline Clomiphene ciate Sldenal Testosteone eplacement theapy
95
Answers and Critiques Item 1
Answer:
B
Educational Objecive: Trea hypehyroidism duing pegnancy.
his paient has hperhyoidism occurring durng pregnancy and should be treaed with propythiouracil (PTU) . Based on this patent's age and sex, the mos lk ely cause of her hyper thyoidism is Graves disease Clinical ndings supporting ths dagnoss are the diuse thyomega thyroid bit and elevated hyroid-simuating immunoglobuln index. Teat ment of hyperthyroidsm during pregnancy s ypcally with medical management and PTU aher han mehimazole is the dg of choice during the rst trmester Although rare methimazole has been associated with deveopment o aplasia cutis (absence of a poton of skin on the scap in a localed or widespread area and choanal atresia (bockage of the posteror nasal passage due to ied recanalizaton o the nasal ssae during fetal development when used in the st timester. Once organogeness is complete methimazoe can be substited PU Methimazole s typically the pre ferred agent in patients wth hyperhyodism because i has a longer intrathyroida hal life than PTU and usually can be adminstered once daily. Radoactive iodine is contraindicaed during pregnancy because t can cause destrucion of the fetal thyroid. 1yroidectomy is generally avoided duing pregnancy unless he hyperthyroidism cannot be controlled o the patient cannot tolerate either PU or methmazoe When needed surgery is typicaly permed during he second trmester if possble
roidism due to multiple gland hyperplasia requenty occurs in patients with MEN2A Patients with primary hyperparathy roidism may present with symptoms related to hypecalcemia ( polydipsia polyura and constipation) or the hyperparathy roidism may be und during an evaluaion r osteopoosis or nephlithiass Pheochmocytomas in MEN2A are usu ally benign and intraadrenal in ocaton but can be multple or blatera nsulinoma and polactnoma occur n mutipe endo cine neopasia type MEN) [n MEN one mutated allee of he MENl gene is usualy nheited and a somaic muta on in the other alele is ater acquired and results in the r mation of neopasia Ie most common endocrine disorder in MEN is pma hypeparahyroidism resulting om one o moe paahyroid adenomas. Neuroboma is not a clincal feature of MEN2A Neu robromas caf-aulait spots and pheochromocyoma are among the clinical feaures of the autosomal dominant dis order neurobromatosis type K POIN
• Medulay thyroid cancer pheochromocyoma and prmay hypepaathyoidism occur in patents wth multiple endocrine neoplasia type 2A (MEN2A Bibliogaphy Kap GW Noon A RET gn uaons gnoyp ad pnop) o upl docrn nolaa p and a edlay yoid cacnoa Cancr 201 Jul 1203):920 -31 PM 699901
KEY POINT
tem 3
• In pregnant patients with hypethyroidism popylth ouracil rather than methimazole should be used in the first trimester because of the teatogenic eects of ethimazole during thjs time
Educational Objecive: Teat poactinoma durig pegnacy
Biblogaphy Lazams JH. Manageent of hyptyroid in prnancy Edoc 01 Mar;45(2):90 - 4 [PMID: 274179]
Item 2
Answe:
C
Educatioa Objective: Diagose the mutipe edocrine neoplasia type 2 (MEN2) syndrome
m m hh roidism He has symptoms related to caecholamne excess rom a pheochomocytoma and has a personal and mily history of medullay thyoid cancer his is typcal of multi ple endocrine neoplasa ype 2A MEN2A resuting om a mutation n the potooncogene Primary hyperparathy-
Answer:
B
e paient should undergo rmal visual eld tesing During pregnancy there is conce that polactinomas can gow due to estogenic stimulation e risk of signicant growth depends on the sze of the prolactinoma pio to pregnanc With microadenomas (<0 mm) the risk s considered to be lo whereas the risk s highe with macoprolactinomas (�0 mm) Sgnicant expansion may cause vision loss by compressing the optic chiasm t is therere appropriate to obtain vsual eld testing during pregnancy in women with macoadenomas even without symptoms to diagnose vision eld loss (such as bitemporal hemianopsia that may be due im h wm ommended eve imester of pregnanc ecause this patient is in her st trimester and has a histoy of a macroadenoma visual ed tesing now is idicated It is no hepful to check he serum prolactin evel Pro lacin is normaly elevaed in pregnancy and can be greater 97
Answers and Critiques
than 200 ng/mL (00 µg/L). Additonally ths paient has a known proacinoma so her prolactn wl kely be eevated r both reasons Elevated prolactn itself is not necessarly harmful Prolactnomas cause concern when they cause hypogonadsm or mass eec n ths patent, an eevated prolactn level wl not change the reament plan because t s expected to be elevated and does not hep cari wheher the prolactnoma s causng harm. Rotne montorng of women wh prolacnomas wh MR during pregnancy s not ndcaed because the absolue risk of signcant enlargement of ptutary adenomas is low However MRI s ndcated n women wth a ptuary macroadenoma and abnormalities on vsual eld testng or change in headache possbly attrbable o expanson of the adenoma Bromocriptne s avoided n pregnancy when possbe because ts safety during gestaion has no been establshed although when a patent has symptoms of mass eec durng pregnanc bromocrptne may need to be restared How ever woud not be appopriate to esart dopamne agonst therapy in hs paten withou a clear ndcaton r treat ment such as an enargng ptutary adenoma KEY POINT
• Because prolactnomas may ncrease n sze n preg nant women and lead to loss of vson, cose cnca l montorng and rmal vsua eld testng should be perrmed during each rimeser
measuring the gucose level at 3 AM. edcaons that aect the overnght gucose level need to be decreased f he 3 A glucose level s low Medcaons that aect the overnght gucose should be ncreased or added f the 3 AM glucose evel s elevaed Fast-actng insun such as nsun lispro at bedtme ncreases he rsk of hypoglycema Metrmn wll decrease gluconeogeness from the lver and mprove sing hyperglycema However r smlar reasons, overnght hypoglycema must be excluded bere ths treaen could be safely ntated. ncreasng the nsulin glargne dose could aso worsen overnght hypoglycema f tha is the cause of the stng hyperglycema Despte the hemoglobn A 1 evel of less than 7%, the etolo of the paient's stng hyperglycema should be nvestgated Deecton of overnight hypogycema would necessate mmedate changes n her nsulin regmen or od intake regardless of her hemogobn A value. 0
KEY PONT
• Overnght bood glucose montorng can help detect hypoglycema or dawn phenomenon Bbograpy Cye P. Axeod L Gossma AB e a auao an managemet o ad hypogycc dsor a Edocn oc Cnica Pacc Guidene Ci Eocio Metab 2009 Ma:94309 28 [PMl 908855]
Bibliography Melmed S Casanueva F, Hofa AR. et a Dagosi a tratt of hypepoacima a Edoci oci cica acc gudi J C oco Meab 2011 eb:96(2 )273-88 [PMID 229699
Item 4
Answer:
D
Educational Objective: Manage overnight hypoglycemia.
his paent should measure her blood glucose level a 3 AM. he eolo of luctuatng stng gucose values n dabe es can be multctoral, ncludng overnght hypoglycema dawn phenomenon or nadequate insuln doses. To mantain normal bood glucose levels upon rsng, an eary morning physiologic release of catecholamnes cortisol and growh hormone occurs to stmulate endogenous glucose produc on from he lver. Overngh hypogycemia caused by over treatment of dabetes or prolonged eecs of recent physcal n n w -n n n ampl the release o catecholamnes corsol groh ho mone and glucagon o ncrease endogenous glucose produc ton whch can ead o hyperglycema Somo eec) With the dawn phenomenon sng hyperglycema occurs n the seting of nadequae basa nsuln coverage o mantan the endogenous glucose value wthin a norma range Food ntake n the evenng can aso contrbute to sting hypergycemia f it s nadequately covered with insun Overnght hypogy cema and the dawn phenomenon can be dsngushed by 98
Item 5
Answer
A
Educationa Obective Evauate the cause of Cushing syndrome
he most approprate dagnostic test to perform next s a CT scan of he adrenal glands s paten was suspected to have Cushng syndrome (CS based on pathognomonc clncal ndngs and s not takng exogenous glucocorcoids. Two screenng tests r CS are abnoral whch s adequate to estabsh the dagnoss he nex step n evaluaton s mea surement of the plasma adrenocortcoropic hormone (ACTH evel to derentiate be\een ACTHdependen and ACH-in dependent CS Wth ACTH-dependent causes the plasma ACTH s usually greater than 20 pg/mL (44 pmo!L) How ever he low plasma ACTH repoed n this patent is conss tent wth ACH-ndependent CS A CT scan of the abdomen to evauae he adrenal glands is therere ndcated because the n -npnn no and cacnomas of the adrenal cortex neo petrosal snus sampling and MRI o the ptuitary gland are used o conrm the presence of a corcoroph ade noma of the puary gand n ACTH-dependen CS whch s the most common cause of CS overal However nether is ndicated n ths patient because bochemcal testng has no revealed CTH-dependent CS he diagnoss of CS requres that at least wo rst line screenng tests be abnormal ncludng the low-dose
Answers and Citques
dexamethasone suppression test (LOST) (both standard and ovenight), 24-hour urine fee corsol UFC), o lae-ngh salivay corisol. is patient led to suppess corisol levels llowing an overnight LOS and had an elevated 24-hou C level conrmed by a repeat coecion herere measurement of ate night saivay corso is unnecessary because the diagnosis of CS has aread been establshed KEY POINT
• CT of the adrenal gands should be perormed in patients with ACTH-independent Cushing syndrome because adenomas and carcinomas of the adrena cor tex are common causes.
development of keoacidosis whch would requre estarting insuln herapy Determining auommunity, in conjunction wih beta cel function, is helpful n assessng whether a patien has he poenal to become nsuin-independent n the fuue. His auoantibodies wee negave at he time of his pesen tation and t is unlikely that these would now be positive. It is not necessay to eest antibodies in his setting KEY PONT
• Prior o switching om insuin to oa theapy n patients with ketossprone diabetes sting C-peptide and glucose levels should be checked.
Bibliogaphy
Biblogaphy
Nieman L Biler BM. Fdling JW. e al The dianosis of Cushing·s sydrome: a Endocie Sociey Clinica Pacce Gudee J Cin docio Mea 2008 May93(5):56-40 [PMID 183358]
Madoado MR. Onao M, Ceema . et a acos associaed w nsu li disconiuaon i subjecs wih keosis-proe diaees u peseved �-cel ucio Diae Med 5 ec():174-50 PMID: 640322
ltem6
Iem 7
Answer:
D
Educational Objective: Manage ketosis-pone type 2 dabetes meltus.
is patent should have a repeat measurement o st ng C-peptide and glcose levels e has keosisprone type 2 dabetes mellius. Paients with ketosisprone type 2 diabetes do not ful the cassic phenotype associated with autoimmune type 1 diabetes ese patents ae often older, overweght o obese, and of back or atino ethnc ty. Patients with new-onset eosis-prone diabetes requie nsuin therapy initial but might be able to be managed wth oral agents in the future. Pior o switchng om nsuin to oral therap his pancreatic bea-cell ncion shoud be assessed wth stng C-peptide and glucose mea suements Ketosis-prone type 2 diabetes is heteogeneous condition in that the presence of autoanibodes is variable acoss the population as is the degee of pancreaic bea cell uncton. His initial C-peptde evel in the seng o hype glycemia and dabetic keoacidosis is no an accurate indi cation of his panceatic uncton. Due to the toxic eects of proonged hyperglycema on the panceaic beta cells the sting C-peptide and gucose or a glucagon-stimuated C-peptide should be measured 7 to 1 days afer the coec tion of he acdosis in orde to better assess functon. I his repea stng C-peptde value s geaer than or eual to 1.0 ng/mL 033 nmol/L or his gucagon-stmulated C-peptide value is greater than or equa to 1.5 ng/mL (05 nmol!L his bea cel uncton is preserved A sliding-scale nsuln regimen that does no nclude basal insulin and does not begin insuin admnisraton unless the blood ucose eve is at o above a threshod level wil cause wde swings rom hperglcemia to hypoglyce ma and this is inappropriae treament Discontnuaton of his insulin and swiching to an oral agent such as metrmin could be atempted wih evdence of bea cell uncion preservation Cose low-up woud be necessary to monitor r worsening hyperglycemia or
Anse
C
C
Educatona Obective Teat pitutary apopexy
e e v v Gv ev e ee e e e u e ee e v v p e ' w · v e ' : W w v v v v > KEY POINT
• Patients with pituitary apoplexy and vsion loss should eceive immedate stress-dose glucocorticoids n aton o unergong urgent transspenoia pituitary decompression. Bibiogaphy Raaseaa S Vadepump M Badeweg S e al UK gidees the anageen o piuiay apoplexy C ndoco 0 a;74(:9 MD: 019] 99
Answers and Citiques
Item 8
Answer:
B
Educational Objective: Manage a soitary thyoid nodue. Fine-needle aspration (FNA) is the most appropriate next step n he evauation to determne whether this patient's thyroid noue s maignant or benign. She has aready had an utra sound examnaton Utrasonography is a sensitive means of identng nodus and povding further characterzaton of the nodues, which s more preictive o malignancy than size aone e utrasonographic features that are considered more suspcious r maignancy incude hypoechogenicty, mcro caccations, rreguar margins, and increased ntranodular Dopper o According to Amercan yoid Association gudenes, this patient with a hypoechoic nodue that is .5 cm shoud have an FNA to re out magnanc Nodular features are not readiy dented on CT, and this study has a ower sensitivy than ultrasonography r identing the presence o nodules CT o the neck woud therere not provide any additiona inrmation about this patient who has aready had an utrasound examination. In addition, CT woud expose ths patent to unnecessay rad aton. f a patient has a substea goter, CT is benecia r determining the extent of the goiter However this patient has no extenson of the thyroid nto the mediastnum Levothyoxine therapy to suppress growh of benign nod ues s no onger recon1ended Randomied cca trias have ied to show a sgcant eect on nodue voume. Adtion a, the requred dose can induce thyrotoxicoss, which is asso ciated wth signcant risk for cariovascuar compications Measurement of the serum thyrogobuin eve is reseved r patients who have had a tota thyrodectomy and is usefu as a tumor marker r detection of residua or recurrent thyroid cancer. In a patient with an ntact thyroid, serum thyroglobuin measurement is an insensitve and nonspecic means o testing r malignancy yrod scanning with technetium is unikey to be hepfu in ths patient. hyroid scanning is used to deter mine the nctiona status of the odue sotope scannng is most use in the seting of a nodue accompanied by a ow serum thyroidstimating hormone eve because toxic (or hyperunctoning) nodues ypicaly do not reure FA as the vast majorty are benign. is patent has a norma sem thyroid-stimuating hormone evel and is likey to have an ndetermnate resut ("cod or "warm) on thyroid scanning. KEY POINT
• ineneede aspration is the most appropriate next step in the management of a patient with a soid thy roid nodue measurng greater than cm on utra sonograph Biblogaphy American Thyid Assoain (AA) Guidees skf o hyroid Ndles and Dieretied hyrid Caner, per DS. hery GM Hg BR l vi Ami hyid oitin mn gdees fr pies with thyroid ndes nd direnid hyid er hyr 2009 :91167-24 Ertm i hyri 2010 A089 [PMI 1980577
100
Item 9
Answe:
A
Edcational Obective: Manage pimay amenohea e most approprate management is to initate estro gen and progestin therapy in this patient with primary amenorrhea Primary amenorrhea is dened as the ack o menses by age 6 years accompanied by a norma body har pattern and norma breast deveopment. Pregnancy must be ruled out in al patients wth primary amenor rhea Approximatey O% of patients wth primary amen orrhea have a chromosomal abnormaity Prmary ovarian insucency due to Turner syndrome a syndrome char acterized by short stature and the oss of a portion or a of one X chromosome, s one of the most common causes o primary amenorrhea. 1e diagnoss of Turner syn drome can be made on the basis of a karyotype, and this shoud be the next diagnostic test r this patient. Such a patient may aso have fragie X premutation; however, no cogniti ve impairment is typicay seen in this patient pop uation agnosing urner syndrome is critical because aected patients have a high er incidence of cardiovascuar disease, metaboc syndrome and thyroid dysfuncton. Patients wth Turner syndrome may have either primary or secodary amenorrhea and commony have normal secondary sexua characteristics e mechansm invoved appears to be eary licuar depletion, such that ovaries are devod of icles and oocytes. Serum evauations n these patients wil reveal ow estradio eves typcay below the detectabe eve in the assay) and markedy eevated gonadotropin eves s constelaton of nd ings is consistent with hypergonadotropic hypogonadsm Such patients shoud receive hormone repacement ther apy wth estrogen and cycic progestn to prevent endo metria hyperpasia, osteoporosis, and other seuelae of hypoestrogenism. A pituitary proactinoma causes secondary amenor rhea through direct inhibition o gonadotropinreeasing hormone secreton by proactin. Because this patient has eevated evels of gonadotropins, nether a ptuitary MR nor a prolactin measurement is necessay Both hypothyroidism and hyperthyroidism aso cause seconday amenorrhea Hypothyroidsm resuts in ncreased eves of thyrotropnreeasng hormone through negative feedback, and this hormone in turn, stimuates proactin secretion and suppresses gonadotopin secretion Hyper thyrodism can cause rapid weight oss, whch is known to cause functiona hypothaamc amenorrhea. Since this patient has eevated gonadotropin eves and no sgns of hyperthyroidism thyroidstimulatng hormone measure ment s not needed. KEY PONT
• atients with primary amenorrhea associated with hypergonadotropc hypogonadism shoud receive hormone therapy with estrogen to prev ent endome tria hypepasia and osteoporosis and cycic progestn to prevet endometria hyperpasia.
Answers and Citiques
Biblogaphy Cordts EB, Chistofolin OM Dos Santos AA inco . rbos CP Geneti aspets o pemue ovn ilu e: a itee revie Arh Gyneo ste 201 Mr283(3):635-43 [MI: 880]
Item 10
Answer:
B
Educatonal Objectve: Treat subacute thyrodts.
AP-blocker, such as meopoo is he most appopiate teat ment his patient with thyrotoxicosis who has subacute ganuomatous (de Quevain) thyoiditis based on the ow adioactive iodne uptake (RAJU) and he pain thyoid on examination. An anteceden even, in his case a via i ness, destoys the thyoid ices and igges the reease of pemed thyoid homones into the boodsteam ceatng the thyotoxic phase Duing ths phase the eease o thyoid homones ceases esuting n a ow RAJU as seen in this patient P-Bockes ae benecia n he thyooxic phase to bock the adenegic eects of the high cicuating thyoid homone eves Teatment o subacute thyroditis is othe wise typicay supporive with NSAIDs pain as needed In patients with severe pan gucocoticoids may occasionay be used. Bocking uthe eease o hyoid hormones with a thionamide (eithe methimazoe o popythiouaci) is ine ective because the hyod has aeady eeased pemed thyoid homone ino the boodsteam and is currenty not pducing o seceting additiona thyoxine Administation o adioactive iodine teamen o he hypethyoidism is aso neective because this patients thyoid is not cuenty takng n iodne as evidenced by the ow uptake on his thyoid scan More importany, adoac tive iodine wi not teat this patient's undeying problem o damaged thyoid ices and eease o permed hyoid homone into the boodstream KEY POINT
KEY POINT
• Antipsychotic agents bock dopamine and decease inhibition o poactin eease at the pituita causing hypepoactinemia Bibliogaphy Memed Csnueva Hfmn AR et al Dagnoss nd teen o hyepolanemi: an Endorine oiey ni re guidelne J Cn Endorinol Meab 20 Fe96(2273-88 [MD: 229699!
tem 12
Answe
B
ducationa Objectve Manage ow bone mass
• eatment o subacute ganuomatous (de Quevain) thyoiditis ypicay is suppotive with NSAIDs and occasionay gucocoticoids sevee pain; P-bockes ae benecia in he thyotoxic phase to bock the adenegic eects o the high cicuating thyid homone eves Bblogaphy Sweeney L Sewrt C Giode DY Thyroidiis: n negred ph Am F hysan 01 Se 906:3899 [MI: 13
Item 11
hypeproacinemia bu shoud ony be done unde the supe vision of a psychiatrist. 1e patiens ispeidone shoud not be disconinued uness he psychiatist is consuted Hypothyodism can cause hypeproactinemia when unconted but he hypothyroidism is we reated She has no symptoms of hypohyoidism and he thyoid unc tion tests ae nomal so unconoed hypothyoidsm is not the cause o he hypeprolacinema Antipsychotic agents cause hypeproactinemia by bocking dopamine, but ihium does not cause hypepo actnemia Ahough he patient has a ikey expanation he hypeplactinemia a poactnoma is si possibe Rspei done can cause poacin eves above 200 ng/mL (200 µg/L), so he eve o 02 ng/mL (02 µg/L) is not uneasonabe Remeasung the pactin eve owing discontnuation o the dug is ecommended bee uthe evauaton a pituitay adenoma he patients psychiarist shoud be consuted bere withhodng he ispeidone testing. A patient with hypeproactinemia wihou a cea seconday o dug-induced cause shoud be assessed by an imaging study (peeraby, RI of the pitutay gand) to a excude pituitary esion
Answe:
D
ducatona Objectve Dagnose ypeproactinemia e y n npy gen
Hypepoactinemia is a known sde eect o antipsychotic agents, and this patients hypepoactinema is ikey due to rispeidone Antipsychotics bock dopamine and decease inhibition o poactin eease at the pituitay causing hyper poacinemia Stopping the medicaon can evese he
A epeat dua-ene x-ay absoptiomey (DEXA) scan shoud be epeated in 2 yeas in his patent wih ow bone mass and eaivey o 0-yea ace risk he Factue Rsk Assessment oo (FRAX cacuato denes the 0-yea ractue isk patients with T scoes in the 0 to - 2 anges e FRAX cacuator (wsheacuk/RAX) inco poaes mutpe isk ctos incuding sex actue hsto emoa neck bone mnea densit gucocotcod use smok ing BM!, age and acoho intake to detemine pojected ac ue isk. I the sk o maor oseopootic actue is geae han or equa to 20% o the risk of hip acue is greate than o equa to 3% then he patients benet rom theapy exceeds he isk, and she shoud be oeed treatment Because o he h bd h d md u k during the time o deveopment o peak bon e mass she is at inceased risk ow bone mass o osteoposis and is there oe an appopae candidate eay screening He DEXA scan shows ow bone mass Spine m shows no evidence o actre Additonay he cacum and vitamin D eves ae noma. Contnuing iestye activities (such as maximizing 10
Answers and Critiques
weightbeaing exercise and avoidance of obacco or excessive alcohol) in addition to cacium and vtamin D supplementation is appropiate management of thi paient Raoxfene is a electve estrogen receptor modulator (SERM) that s a treament opton r women with osteoporosis because it has been shown to incease bone minera densit and reduce the risk of vertebal (but not nonvee bral) ractures. However raoxfene is aso associated with an increased sk of homboembolc events and vasomotor symptom here is limited data suppoing use of alxiene or oher SRMs r treating patents with ow one mass, athough some guidelnes recommend consideng treatment n patients wth low bone mass and 0year facture risk determined by the FRAX calculator of geater han or equa to 20% a major oseoporotic racue o greate than or equal o 3% r ip fracure. Raloxifene would therere not be appropriae theapy for thi patient Choecacfeol (D, a metaboite of vitamn D s com mony used to supplemen low serum vitamn D levels in patients with viamn D deciency his patien has noma serum vitamn D levels; theere there is no indcaon r treamen wth vtamin D metaboles. Bisphophonates are consideed rstline therapy r osteopoross, athough they ae not used rounely in women wth ow bone mass. Smila to the use f SRM therapy gudeines ecommend consideation of treamen wth a bisphsphonate r low bone mass only f there is 0year actue risk determined by the RAX caculator of greaer than or eual o 0% fo a major osteopooic fracure or geaer than or equa o 3% r hip fracture. KEY POINT
• reatment r low bone mass in postmenopausa women involves lifesyle modfication (maximizing weightbearing exercise and avoidance of tobacco or excessive alcoho) and vitamin D and calcium supplementation the need r pharmacologic therapy is based on the 0year etimated acture risk (:20% r a major osteoporotic acture or 3 r hip acture)
du ue ines i n e eum to idhonine T ee e em t iimu r nd erum ee thie T ee my l dece he e inrese n ei ! pte ee e reu ten idiushe ee wth n I pothdism n t oe cnLe ei bu ee he cnc pur w e ee nd o u T 1 nd � ee n dpe epone he crtc e t e te bdys metim d hreby id rve o e ue i ness i pien de n e ny deie nn un Ge diee 1e chdi d eer re e e eut of s eere ncn I he w o epeecg thod storm i eum I nd T3 ees woul m liey e aaed wh e w e T ccet i e o cmmo cue hpoi i id Phc emino dn ca icue reuce l empeue dtc yerte n enrged hi g and rdcrd po ad d n bte rene d deed ece p deep tedn eee ie w hmot thditi e w nd T ee and eeted i ptient' w T eve copte w Hhmoto thidt paient uniey to hae ucue tyrd ed on he mn o e nes Althu e nctn ud hve triggeed desucion f the hri the sube ue eee o preored tyid hre in e erum hud eu in ee f eum 4 ee in th e he the diee whc nt net wth he id i hs e KEY POIN
• nless there is a song suspicion o a n underlying thyroid disorder that may be contributing to a patiens cinical indings thyroid nction tests should not be perrmed during criical illness because test results are highly likely to be abnormal Bibliography
Bibliography Kng JM. Carke BL Sadhu N Osteopooss evenion, screein and emen: eew Womens Heal 2014 u3(7):563-72 [PMI 247668]
Fawel A onhyodl ilness syndroe C rr Opn Endoinol Dbees Oes 203 O204884 M: 397778]
Item 14
C
Item 13
Answer:
A
Edcaal Objectve: Dagnose euthyrod sik syndrme.
i pie· c e e wi euod i d c nnhyial ine drme U ee i tn uspicn n undein d drdr my e ctruti t ptient' cinic ind s id uctn e hu t e pemed duing ii i In opite ptient peci ons as h pi erbe ee hd uc te u re ie e e deiio h y 102
B
duatona Obetve Libeaze yem tarets n a patient wth mutpe diabeti ompiations and advaned movasua dsease
1e most appropriate next step n management of this patient s o decrease the rsk of hypoglycem by decreasing the insulin dose deliveed by the pump. is patient has had type diabees r 25 years with subsequent development of advanced microvascula disease. Hs frequent hypoglcemic events and hypogycemic unawaeness incease the risk of morbidiy and mortalty fom recurrent hypoglycemia that may occu with stringent glycemic goas. Glyceic goals should be individualied to account
Answers and Critques
r patient-specic ctors, such as age and comorbdites. he American Diabetes Association suggests a hemoglo bn A goal of ess than 8.0% n patients with a decreased life expectancy history of severe hypoglycemia multipe comorbidities, or advanced microvascular or macrovascular disease e less stringent hemoglobin A goal should be impemented to avoid recurrent hypoglycemia; however the goal may need to be increased above 8.0% if it cannot be achieved safel Altering the pump settngs to deliver more insulin to attain a hemoglobin A goal of less than 7.0% will increase his isk of hypoglycemia. His hemoglobn A goal should be liberalized to avod hypogycemia. e risk of hypoglycemia can be educed wth lower insulin doses delivered by either an insuin pump or sub cutaneous injections. Snce the patient is aready using an insulin pump alteration of his insulin pump settings to deliver less insuin should occur next. Gabapentin r treatment of his painul peripheral neu ropathy is approprate, but avodance of recurrent hypogly cemia s the most serious issue that needs to be addressed next due to the associated increased risk of morbidiy and mortali 1
e
1
e
e
e
KEV POINT
• A less strngent hemoglobin A goal is appoprate r persons with diabetes mellitus with a decreased life expectanc, hstory of severe hypoglycemia multiple comorbidities or advanced icrovascular or macro vascuar disease 1
e
Bblography American Dabetes Associaion. (6) Glycemc argets I: Sandads of Medical Care in Diabees-015 Diabees Care 0 Jan38 Supp S33 40 [PMD: 23770
Item 15
Answer:
D
Educational Objectve: Detemne causes of vitamn D defcency.
is patient with reactory vitamin D decency despite aressive attempts at repletion, shoud be screened for celiac disease. e ct that supplementation with a theapeutic dose of vtamin D has iled to replete her body stores shoud raise concern for a malabsorption disorder. Based on her his tory of another autoimmune disorder (vitligo) ower ange M! and nonspecic signs and symptoms such as tigue, subclinical celiac disease would be a reasonable cause o her malabsoption. Celiac disease may present with classic symptoms of diarhea overt malabsoption, and weight loss bu ma al in a mild rm and ma ar undetected snce patients have ony nonspecc symptoms and subclinical alabsorpton. If this patient tests positve r celiac disease, removing gluten om her diet will impove her intestinal lnng and impove absorption of vitamin D. Even with therap patients wth malabsoption will likely requre increased doses of vitamin D supplementation.
Paathyroid imaging wth a sestamibi scan is not indi cated because the patient does not have primay hyper parathyroidism. He parathyroid hormone level is elevated as an approprate physiologic response to her markedy low vitami D eves. Once her vitamin D levels are su cient (>30 ng/dL [75 nmoL]), he parathyroid hormone level shoud be emeasured to ensure that it has returned to the noma range. e parathyoid hormone leve should be remeasured n approximately 4 weeks. Referra r paathyroidectomy would also not be ndi cated in this patent without an established dagnosis of primay hyperparathyoidism. A person he age wth noma diet and mnima sun exposure shoud require about 000 U daily of vitamin D to mantain adeuate vitamin D stores e choice to use chole calcferol versus ergocalcfeo is often based on the evel of vitamin D dect. Since the ergocalciferol is more readily available in the 50000 U m and has a shorter half life, it is ecommended when a patient's vitamin D level is less than 0 ng/m (25 nmol/L) Choecalcferol s often used when the level is between 20 and 30 ng/m (50-75 nmol/) or r maintenance and therere would not be ideal to replete this patient. Cinica discretion can be used r levels between 0 and 20 ng/mL (25-50 nmolL) Although vtamin (choecalcfer) is a reasonable option r treatment of vitamin D decienc, as mentioned above cholecalciferol is best used mantenance of vita min D levels or repletion when the 25-hydroxyvitamin D level is between 20 ng/mL (50 nmol/) and 30 ng/mL (75 nmo/) Neither rm of repletion, however wil be eective in the presence of signcant malabsorpton. 3
KEV POIN
• Wen vitamn D repeton eorts l, secondary causes, such as malabsorption, should be considered. Bibigraphy Tvko A DGiacoo D Gee H, Lewhl B Viam D sats and con coman aoimmnity i ceac disese J Gasroeeol. 203 l(:59. MID: 23328299]
Item 16
Answe:
A
Educationa Obectve: Treat subclinical hypothyoidsm
he most appropiate next step in management is to initiate levothyoxine theap. hs patient has subclincal hypothy oidism with a mild elevation o the seum thyroid-stimulat ing hormone (TSH) eve and normal serum ee thyroxine (T evel Her mily history o hypothyoidism and her thyoid eoda abod o ra eod po gression to overt thyoid ilure. ln patients wth a mild serum S eevation (between the upper mit of norma and 0 µ/ m [10 mU/L), beginning levothyoxine theapy is reasonable if symptoms suggestive of hypothyroidism are present. yroid-stimulating immunoglobulins (TSs) are highly associated with Graves disease. When the diagnosis of 103
Answers and Citques
Graves disease cannot be made clinically in a paen wih hyperthyroidism, measuremen of he serum level of hese anibodies is recommended especally i radioacive iodine upake studies are no avalable or if radioac ve odne expo sure is conraindicaed as n pregnancy and breasfeedng. his paien does no have hyperthyroidism and hese ess are herere not indicaed Repeaing a serum TSH measuremen in this paien was reasonable since up o 30% of paens with an iniialy abnormal serum TSH level wil have a normalizaion of his value upon reesng. Since his paien has persisent elevaion of TSH and sympoms ha may be aribuabe o hypohyroidsm waing 12 monhs bere iniiaing herapy is no approprae A radioacive iodine upake (RAJU) scan s reserved r patens wih hypethyroidism Paiens with Gaves disease ypically have an eevaed RAJU. Conversel n paiens wih hyroidis or exposure to exogenous hyroid hormone he RAJU will be ow (<5%) despie biochemical hyperhyroid ism Obaining a hyoid RAJ in his paien is no indcaed KEY POINT
• Levohyroxine herapy is reasonable in a paien wh subclinical hypohyoidism and sympoms suggesive of hypohyroidism Biblography Grber JR. Cabin RH. Ghrib et l; Aercn Associio of Clincl Endocnologss nd Americn Thyrod Associon Tskorce on pohodsm in Aduls Clinc pcice udelnes r pohod is n dus cosposored b he Amerc Assocon o Clncl Endocnooss nd e Aecn hod Assoco Endoc Pc 2012 Nov-Oec:18(6)988-1028 E n Endoc Pc 013 Jn Feb;9(175 [PMID 23246686]
Item 17
Answer:
C
Educatoal Objectve: Define sugica indcatos for pmay hypepaathyrodism. he mos appropriae reamen recommendaion r his patien is parathyroidecom She has prmay hypepara hyroidism as shown by her elevaed serum calcium and parahyroid hormone evels She also has evidence of kidney compromise wih an eevaed creainine level and decreased esimaed glomeuar lraion rae (eGFR). Impaired kid ney funcon (dened as eGFR <60 m/min/173 m 2 , 24-h urine calcium >400 mg/24 h [10 mmol/24 h], o he presence of nephrolhiasis or nephrocalcinosis by radiogaph ulra ond o i n indiion gi een ohype parahyroidism n oherwse asympomaic paents Oher ndicaions r surgery in asympomatic patiens include age younger han 50 years; a serum calcium level greaer than or equa o 1 mgd (025 mmol/) above upper limi of nor mal; a -score of -25 or worse a he lumbar spine otal hip femoral neck or disal radius: or n those n whom medca surveillance is neiher desred nor possibe Paiens wih hese indcaions are considered o have he highes poentia benet rom surgery.
104
A bisphosphonate such as aendronae would no be he reamen of choice r his paien as she does no have oseoporosis nor does she mee Fracure Risk Assess men Tool (FRAX) crieria r therap e FRAX calcuaor denes he 10-year racure risk r patients wth T scores in he - 10 o 25 range he FRAX calculaor (w wwshef ac.uk/FRAX) incorporaes mulipe rsk cors incuding gender acure hiso femoral neck bone mineral dn siy gucocoricoid usage smoking, BM! age and alcohol inake o deermine pojeced racure risk f he risk of major osteoporoc acure is greaer han or equal o 20% or he risk of hip acture s greaer han or equa o 3% he paien's bene om herapy exceeds he risk and she should be oered reatmen Addionally bisphosphonaes should be used wi h cauion in paiens wih compromsed kidney funcion. f he paien declines surgica inerventon a cac mimeic agent such as cinacalce would be an appropriae herapy. Cinacalce has recenly been FDA approved as an alernaive r paiens unable or unwiling o undergo paa hyroidecom Cinacalce owers calcium levels by simula ing he calcium-sensing recepors of he parahyroid glands and inhbiing parahyroid hormon e secreion However, i is expensive and has muliple drug neracions which make i less desiable in his paien ecause his paien s considered o be a increased rsk of complicaions due o unreated hypercalcemia cinical observaon alone would no be appropriae. KEY POIN
• D ecreased esimaed glomeruar filaion rae <60 m/min/13 m 2) is an indicaion r surgical ea men of primay hypepaahyroidism in oherwise asympomaic persons. Bibography Blezki J, nd ML Esel R Siverer SJ Udesmn R Mrcocc C e l Gudeines he Mneen of Aspoic Prim peprhodism Smmr Semen ro he orh Inernion Worshop Cin Endocrio Meb 099(0569 MI 2562665
Item 18
Answe
C
Educatioal Objectve: Evaluate a toxc thyroid odue Perrming a radioacive iodine ( 123) upake and scan is he most appropriae managemen for his paien who mos likely has a oxic nodule or nodules as he cause r her mil d ypeyoidm. ine mupe node ee denied on ulrasound i s imporan o ascerain which of the nodules are auonomous as he likelihood of maignancy in such lesions is very lo. Perrming a hyroid scan will hep iden i wheher one or more of he nodules is responsible r her hyroid ncion abnormaliies A hyroid scan will also deermine if ne-neede aspi raion s indicaed elsewhere in he gland Nodues ideni ed as auonomously funcionng or "ho) do no require ne-neede aspiraion whereas nodues ha are either cold
Answers and Critiques
or "warm (of mar upake o the uronding non-noduar hyrod tue) may requre cyoogc evauaon. T paent may umatey benet om mehazoe theapy, but nce her hyperhyodm md ae o wa o ntae medca heapy un aer he thyrod can perrmed n paent h a reaer deree of thyoox co bennng methmazoe o ower he thyrod hormone eve por o perrmng addtona etng reaonabe. Once the horone eve are nearng he noma range the honamde hod be whhed r s day pror o he hyod can. f the paent und to have toxc nodu e or mulpe oxc nodue, urca remova a reaonabe reatment approach, pacuary f here are compreve ymptom fm the goer Snce th condered an eectve proce dure admnteng ow-doe methmazoe o normaze of her hyrod hormone eve oud be advbe po to urgery KEY POINT
• Perrmng a adoactve odne (123 thyrod uptake nd can the mo approprae nta managemen r a patent who ha d hypehyodm mo key cued by a oxc nodue or ndue Bibliography Jameson JL Miniizing unneceay sugey r thyd noule. N En J Med 2012 Aug 23:367(8)765 - [PMID 2273167
Item 19
Answer:
A
Educational Objective: Treat a macroprolactinoma.
The paen ha a macopoactnoma, whch be eaed wh a dopane agon uch a cabegone he mo com mon caue f hypepoacnema a proacnoma hch a bengn adenoa Mcropoactnoma are e han 0 mm n dameer and mcoproacnoma ae 0 m geater n dameer. Proactnoma are he mot common type of ecetoy putay adenoma. e paent or caung gncant ma eec ncudn compreon of h opc cham nvaon n the cavernou nu econday hypo hyodm and key owh hormone decency; however even wh thee compcaton, the macoproacnoma be treated wth medcon nead of urgery A dopamne agon can cau a apd decreae n the eum proacn eve and hrnkage of he prolacnoa More peccay n a many a 90% o paen can normaze proacin eve revere hypogonadm and hrnk mor by a eat 50% Becaue o hee rapd decreae n tumor ze dopamne agon can be ued a rtne hp even n paten w d va ed de a a via ai n hreaened by rapd proreon o he 1mor or recen umor hemorrhage Octreode ued to trea acromegay bu t ha no roe n the rtne treamen of poacnoma Medca heapy preferred over urgey and adaton r the reatment of proactna Stereoactc urgey a
pecc knd o rdaon herapy wod be condered n a paen wth a tumor ha reactoy o medca herapy and ncompeey reecabe Becaue th paen ha a proacnoa he reatmen of choce a dopamne gon, no urery here an exceen chnce ha he poacnoma l epond o cab ergone, and he paen can avod ugery. KEY POINT
• Dopane agont, uch a cabergone, are frtne herapy r ymptomatc paten wth proacnoma Bblography Meed S Caanueva F, Homan AR et a iagni an teate of yepoaineia n Enine iety lina racice guidelie Cn Elc Metab 2 eb962273-88 MD 2296991]
Item 20
Answer:
B
Educational Objective Diagnose hypoglycemia in a patient with diabetes mellitus taking a sulfonylurea.
Hpyi s h ky au hi pen d n su I pi kng sunyr r db h dvp dhydi uch h pn wih drd r k in jni h naua and vom ng pd kdny pru ay d ard phr ckcs d n d rk o hpyc red nng s h dio d n car hyd nk hh nyuras very cv nhperm n mo n hv rlaivy h vs n nvn . Hwevr h rn prdip hypci c p h her yc mdon pricury h kdn unn i pr d. Gyd prcur hs nr h hn h nea nd u cndd s n d pn h Ber C di h hud vd r ud wih o p hh h ok gprd Lh 24 h b her prn h red s. sh dhdd hu pnin h c- h u cg r v huh pin h d a ncd rk r hs cdvr da h p d no h ca n ng ceevcr cidn nd srke n cn cue aed n u vhn s h riv ha ie aow n d dn o pn ing e o ev e o vohyi wd hr no ikey d r iis us u u chn. i c s unu nd h cn iy scd h s u ucuk ypto rd vs r n picy ocad wh mn u he d ud ikey o be th ae h pin' ss ch. 105
C
Answers and Crtiques
tem 22
KEY POINT
• Sunyureas with ong haf-lives, such as gimepir ide may ead to acute kidney injur y and hypogyce mia in oder persons with diabetes meitus. Biblioraphy American Dibts Assoiao. (7) Apoahe lo gycem eatmn In: Standard of Medica Care in Diabts-2015. Diabtes Care 20 Jan38 Su :S-8 [PMD 25537707]
Answer:
Item 21
A
Educational Objectve: Evaluate trodothyronine (T 3) hypehyrodism.
e seum triiodothyronine (T) eve shoud be measured next. is patient exhibts sgns and symptoms of hyperthy roidism Even though the avaiabe aboratoy data are consis en wth subcinica hypehyroidsm the diagnosic evau ation is no compee unt the T eve is checked. Athough rare an eevated T eve and a norma seum ee thyoxine (T eve may be present in patients with hypethyoidism. Measurement of the T concentation shoud therere be obtained in a patiens suspected of having hyrotoxicoss Measurement of he T eve is not ndicaed in patients wih hypothyroidsm because the T concenration is conserved and may reman wihin he norma range even in patients with signicant hypothyoidism Measuring the hyrod peroxdase (PO antibody titer wi not provide additiona inrmation abou this paient Determining PO antibody status is hepfu in paients wth a mdy eevated se thyrodstimuating hormone (TSH eve and is assocated wih Hashimoto thyroiditis and future risk of deveoping permanent hypothyoidism. owever this patient demonstates signs and symptoms consistent with hypethyroidism Repeaing he thyroid functon tests (TFTs in 6 weeks may be appropriate if the tota or free T eve is und to be norma. If the T is norma the patient has subcinica hyperthyroidism and repeating the TTs may be indicated t o determine if the abnormaty is transient or permanent Utrasound of the neck is appropriae or the eva uation of this patient if a nodue is suspected owever, hs patien's difusey enarged thyroid gand is not suggestive of noduar disease n addition even if he physica examination were suggestive of noduar ds ease t he st se wod be vauaion of the unctiona hyroid status 3
3
3
3
3
3
3
EY PON
• Most patients with thyrotoxicosis wi have eevations of both fee thyroxine (T ) and triiodothyronine (T) but isoated T eevation is rare. 4
Bbography Vada B a SH iagnosi nd managemen o hotoxiosis M 204 Aug 239:g5128 [M 516390 106
Answer:
B
Educationa Objecve Diagnose hypercacema in a patent with sarcoidosis.
his patient most ikey has hypercacemia due to increased 125dihydroxyvitamin D eves She has an eevated ca cum eve with a ow paathyod hormone eve indicaing non-paathyroid hormone (PTmediated hypercacema. he dierentia diagnosis of nonPT-mediated hypercace ma incudes cancer-reaed hypercacemia caused by oseo yic esions of bone hmoray mediated by tumor-secreted parathyroid hormone-reated proen (PTHrP or ganuoma ous dseases such as sarcoidosis n granuomatous diseases the hydroxyase in diseaseassocated macrophages actvey convets 25-hydroxyitamin D to the highy active 1,25dhydoxyvitamin D metabote he increased eves of active viamin D ead to increased absorption of cacium n the gut promoion of increased bone resorpion of cacum and decreased cacium and phosphate excretion by the kidne. evated serum cacium can be due to a mutaon in the Gcouped protein caciumsensing receptor (C gene hese receptors are n he parathyroid gands and the kid neys. he sensor mutation resuts in a shif upward in the "norma range of cacium tha the recepor recognizes resutng in a midy eevated serum cacium eve (usuay <11.0 mg/dL [27 mmo] and high norma or midy ee vaed PT eve unike this patient whose PTH eve was ow 25ydroxyvitamin D s he major circuating rm of vitamin D and is minimay metaboiay active eative to 125dhdroxyviamin D eves in this patient are ikey o be ow due to excessive conversion to the 125dihydoxytamin D rm and woud not identi the key mechanism of hypercacemia in this patient. Hydrochorothiazide a thazide diuretic reduces bood voume by acting on the kidneys to reduce sodium (Na reab sorpton in the dista convoued tubue hiazides increase the reabsorpton of cacium in the dista convouted tubue by heir acton on a Na cacium co-transporter owever any ncrease n cacium caused by thaides is mid and rarey reduces the PTH eve beow he ower ange of norma. +
+
EY PONT
• Granuomatous diseases such as sarcoidosis, cause hypercacemia through increase !--hydroxyation activity that increases 25-dihydrovtamin D eves and cacium reabsorption Bbogaph Shama O Ha mia in grnma dirder a nia revew On um Med 2000 Se65:27 MD: 10958237]
tem 23
Answe
D
Educatona Objective Diagnose Cushng syndrome from exogenous glucococods
he paient has iatrogenic ushing syndrome caused by use of topica gucocorticoids in the treatment of
Answers and Citiques
psoiasis. Cushing syndome presents simila ly wheher is due to a piuitay adenoma (Cushing disease), adrenal tumor cortiso poducion, ectopic adenocoricotropc hormone producion, or excessve use of glucocoticoids. Her presentation would be consistent with any of these diagnoses; howeve, she s on high-potency topical gu cocorticoids so this alone explains her symptoms and presenaion. Exogenous gucocotcod use as a cause of Cushing syndrome is common whereas he othe causes are rare.
KEY OIN
• During the intial management of diabetic etoacido sis, hypoalema shold be corrected bere initiation of intravenous insulin therapy to avoid signicant wosening of the seum potassum levels that could cause cardiac arhthmias. Bibiogaphy Ws J In e cnc Diac koacidosis An nrn Md 00 Jan 552(:C!- MID 008266]
KEY POINT
• The most common cause oCushing syndrome s an elevated evel of cotisol resulti ng fom both endoge nous and exogenous exposure to glucococods. Biblogaphy Neman LK Blr M, Fndling J et al Th diagoss of Cushng's sy droe: an Edocrn Socity cncal pracce gdl. J Cl n docrio Meab 2008 May;93(5)156-40 [PMD 833580
C Item 24
Answer:
B
Edcational Objective: Treat a patient ith diabetic ketoacidosis.
s pe s diabetc ketocdoss OKA d lo seum potssum evel so potassum chlode soud be dms teed. he pet soud be mg dequate ue bee dmjstato o potassum eplcemet. Lo poassum stoes e body need oeco po o ion o nsu teapy to vod cadic ytmas Potassum coide soud be dded to ec e o veous uds o mna the sem poassum eve te 4.0 o 5.0 mEq/L 0-50 mmol nge wth te coiued use o ntve ous nsu 1ep Aboc tepy s o aated t ts me e mid leuocytoss upo peseno s mos ikely eed o stess fom OK he nctous pocess. l dd to e ces dogph s omal. Sodum bicbote povdes o dded beet e the ei bood pH s gete ha 69 d may be sso cated w hm. A 20 systemic eve ud th bcboae dmsaon woseed keoemi Sevel studes ud hge potssum equemets i ptes ecevg bcbone Studes cde und poss be associao beee bcabote tepy nd ceebl edema Dung te etme o OKA to o suli teapy and coeco o acdoss l s e exacel lul potssum bac to e taceul spce. Sg ct oseg o h hyp okalemi oed peseto oud ocu i ts s o coeced to seum poassum level hghe ha 33 Eq/L 3.3 mo/L po o i ion o suln heapy whch coud ed o he devel opmet o ahyhmas Isu epy be sey taed once the seum possum eve s geate t 33 mq/ 33 mmo
tem 25
Answe:
D
Edcational Objective: Identify secondary cases of bone oss pio to initiating bisphosphonate theapy Checng this patient's seum thyod-stimulating homone (SH level would be he mos appopiate test o obtain prior o initation ophamacologic therapy. Although oseo porosis in posmenopausal women is most commonly asso caed with nonmodiable is ctors such as age, sex menopausal status height, and buld t is always important to assess possible secondary causes of bone loss tha mgh be amenable to treatment paticulay if there is clin cal suspcon in a specic patient. Appopiae aboratoy testing mos patients with ne y diagnosed osteoporosis incudes complete blood count maignancy complete metabolic pole r calcium eves and idney function TH 5-hydroxyvtamn and urne cacium (screening r hypercaciuria most of which wee nomal in hs patient. Howeve his paens hisory of uninenonal weight loss ove the pas yea may be he ony sympom of hypehy odsm which coud be conibuting to he osteopoosis and would be mportant o reat n addition o therapy dected towad he oseopoosis. eee, measung this patients SH level would be appopiae prior to satng herapy r oseopoosis. Both seum and uine maers of bone tunover mea sue colagen beadon poducts and othe cemicals eeased om osteoclasts and osteoblasts as part of bone meabolism. Howeve they ae no commonly used n mos paients wih osteopoosis pma ily because thee is signi ican variability in the deent measues in an individual patent o between deren patents mang standad zation o resuts dcult eee hei use s typically imed to eseach sengs o n managemen of specic paients who have iled to espond to usual theapy r oseopoosis. ee s evidence hat estogen is eective peven tion and possibly eatment oseopoosis, although the sgct oseletal iss associed wth this heapy have ed to its not being used in vo of bisphosphonates. As hs paent is postmenopausal and has o clincal sug gestion of excess esadiol secetion and bsphosphonate heapy ould be consdeed pefeable o estrogen despite seum levels esing estradol woud not be indicated in hs patient. 107
Answers and Ctiques
Hyperparathyrodsm should always be consdered as a possible secondary cause of bone loss However, snce this patent had normal calcium and 25-hydroxyvitamn D leves, hyperparathyrodsm would be hghly unlikely and checkng a parathyrod hormone evel would not be ndcated.
KEY POIN
• In women with poycystc ovary syndrome, heavy menstual bleedng, and hrsutsm who do not desre fertl, estrogen-progestn oral contraceptve pls are rstlne therapy to provde endometral protecton and suppress androgen producton
KEY POINT
• stng r secondary causes of bone loss s appropr ate bee begnnng pharmacologc theapy r newly dagnosed osteopoross
Bbloaphy Leg RS, Aslaa SA a DA e al oce Soce Dagoss a eae o poycysc ovary ye a ocie Sociey c cal pacce gelie J li ociol eb 03 Dec98(2)45592 D: 2411290
Bibliography Hudec SM. Camcho PM econry cses of osteoposis Enocr act 203;19:20-8 [MI: 86949]
Item 26
Answer:
A
Educational Objectve: Manage heavy menstrua bleeding caused by polycystic ovary syndome. Ths patent wth polycystc ovary syndrome (PCOS) wth heavy men strua beedng and hrsut sm shoud b e treated wth combined estrogen-progestn oral contra ceptve pils atients wth COS reman in a stagnant lcular stage resultng in unopposed estradol secreton from smal ovarian lcles causng proliferation of the endometrum in the absence of progesterone secreton from a corpus uteum This predsposes patients to endo metra hyperplasa and heavy menstrua bleedng as a result of anovulatory bleedng lntraovaran androgen producton s also ncreased n COS resutng n the hyperandrogenism and hrsutsm assocated with the disorder strogen-progestn ora contraceptve pls are first-lne therapy r the menstrual rreguartes and hrsutsm assocated wth COS Ths therapy prevents unopposed estrogen-induced prolferaton o the endo metrium and suppresses the excess androgen producton assocate d with COS hs would be approprate therapy to treat both ssues n ths patent who does not curre ntly desire fertty Progestn therapy alone, ether through perodc pro gestn wthdrawal or use of a pogesterone-elutng ntauter ne devce wll provide endometral protecton and treat ths patent's menstrual irregularity However progestn therapy alone does not suppress androgen producton and would not treat this patents hrsutsm Metrmn has several vorabe metaboc effects n patens wh COS incudng nceased nsuln sen stvity and reduced serum free testosterone However, t has been shown to be less efectve than oral contracep tves r improvng the menstrual patern and reducng serum androgens t also does not provde endometral protecton and is consdeed a secondne therapy patents wth COS wth signfcant menstrual rreg ulartes and hrsutism who are unable to tolerate oral contraceptve pls
108
Item 27
Answer:
D
Educational Objective Teat adrenocoical carcinoma. Adrenocortcal carcnoma (ACC s the most lkely cause of ths patents Cushng syndrome, and surgcal excison s the most approprate management e patent has cassc clnca manestatons of Cushng syndrome (CS) and the 24-hour urne cortsol s markedly elevated on repeated measure ments lasma adrenocorcotropic homone (ACT s sup pressed consstent with an ACTHndependent cause he imaging characteristcs of ACC nclude a arge mass with irreguar borders or shape, calccaton hgh aenuaton (hgh Honseld unts on CT and delay n contrast medium washout (less than % at 10 mnutes ndngs al present in ths patient e treatment of ACC depends on the extent of ds ease at presentaton Surgcal removal aer appoprate o chemca assessment remans the best opton especally n patents wth early dsease Even after apparent complete resecton, adjuvant therapy wth mtotane a known adrenal cytotoxc drg may be benecal Treatment wth mto tane s recommended r patents wth persstent dsease and others wth known metastases and s assocated with objectve remssons n approximately 25% of patients he man ctors mting the use of mtotane nclude nausea vomtng ethar and neurologc sde eects xperence wth other cytotoxc chemotherapy s lmted but has usu aly een neectve A poorer prognoss s assocated wth advanced stages of the dsease the presence of metastass at diagnoss an older age and cortsol hypersecreton by the tumor n patents wthout clincally evdent dsease after ntal surger the median survval rate s 60% at years Fne-needle bopsy cannot dstngush a bengn ade noma om a carcnoma and s not used in the evauation of ACC t is sometmes used to dstingush ACC from meta statc dsease ts use n this patent is both unnecessary and napproprate Radaton therapy s not used as the prncpa ntal reatment n ACC; however t may e used as adjuvant the apy ater surgery to prevent tumor recurrence Radaton therapy can aso be used to treat areas of metastass such as to the bones or bran
Answers and Critques
Bibiogaphy
KEY PONT
• Surgica removal aer appropriate biochemica assessment is the most appropriate treatment r adrenocortical carcinoma, especially in patiens with early disease. Bibliogaphy Berrti A, Baudn E Geldeblom H et a Adenal cace: ESMO Clical Practice dees dagoss eatmet ad lw-up. An Ocl 2012;23 Sppl 7vi3-38 [MD: 2299746]
c Item 28
Answer:
D
Edcational Objective: Dagnose hypomagnesemia as a case of hypocacemia.
Ts aen's agnesu eve soud be eked He as a vey ow au evel a s ey onung o s na ndings of euousness usce aby and eeo adiog canges e sugges aoo ause and is o aun eve suggess anuon key due o s cron aoo nae as a ay soue o aoes Mag nesu deeny s oon n esons o abuse aoo Fueoe e as ad daea sevea days c aso deee s agnesu soes s aen's o au eve soud oe aayod oone (PI) seeon o he oec e yocaea oweve deeased eves o agnesu a eease of PIH; eves n aens sgnan agnesu deeny ae ee o o na aey n e noa ange Low agnesu eves ae aso associaed essane o PI avy a e eve o one ue onung o yocaea ·1eee aens yoaea and yoagnesea s ua o o e e agnesu eve o a eas 2 g / [083 oL]) as s u o ncease alu eves un s s done 25Dydoxyvan D as a so a e and s easueen ony ees e ave eves o van D Sne ave eves end o vaae requeny based on edae need s eve oud no e dagnosay e l -Hydoxyvan D eves ave a onge a and heee oe auaey ee e oa body soes o vain D easung 4o une au exeon n s aen oud no be dagnosay eu as sgnan unay oss o au s unoon and e une au eve n s aen woud be exeed o be due o o ensaoy dney eenon o au Ceng e onzed au eve s naed n sengs were anoa seu oen bndng o au s ossbe s es s no needed n s syoa aen o as no suggeson o exessve oen bndng o au KEY POINT
• ow serum magnesium leves impair parathyroid ho mone secreton and reuire repetion bee serm calcium levels may be corrected.
Shack D yppaardsm. N Eng J Med. 008 J 2359(4)39-403. [M 865055
Item 29
Answe:
C
Edcational Obective Manage early type 2 diabees mels
Te most appropriate managemen r this patient is to initiate metmin The patient s early in her diabetes disease course without evidence o microvascular dis ease or otherwise healhy adults meeting these crieria he Ameican Diabetes Association recomends a eo globin A 1c eve o ess than 70% preprandia glucose vaues o 70 to 0 mgd .97.2 mo/, and to 2ou postprandial gucose vaues o less than 0 mgd 0 mmol. Because the patent as not met these goals a phamacologic agent should be added at his time. ie sye ecommendations consisting o increased hysical actvty, dietary modicaions and weight loss i B is eevated ae he initial st step in treating diabetes Wen liestye modcaions i to eet glycec goas withn 6 ees metrmin s the ecomended rstline ther ay o be sated in conjunction with continued liestyle modations gycei goas ae not met ate months o liesyle odicatons and etrmin use additional agents shoud be added o te egimen every monhs unt glucose goals ae me. Dapaglilozn a sod umglucose tanspoter2 SG 2 nhbtor increases excretion o glucose tough te kdney. is a second-ine agen that soud be used ater iestyle modicatons and metrmin i to reac glyce mc goas Te sulnylurea gliizide simulates insuin secretion o the ancea bea es. Ts agen coud mprove the aients posrandia hyperglycemia but it may also nduce weight gain in a patient actively woring on weight oss Gipzde s a secondne agent ha should e used ate liestyle modcations and metrmin i to each gycemic goals. Sitagliptin a dipeptidy peptidase- DPP inhib to improves glycemic conrol by s lowing gastric emp yng and suppressing gucagon secetion s aso con sidered a secondine agent ha migt be onsideed i iestyle odications and etmn i o each glyce c goas KY PONT
• or most patients with type 2 dabees mellits, lie style modcations and metrmin therapy are the most appropiate initia eamens. Bibliogaphy Ameca iaees Assciao 7 Appoaces t glcec teatment. In: Sadards of Medcal ae n Diaetes05. iaetes Cae. 05 an38 Suppl :S-8 [MD: 5537707
109
Answers and Critiques
Item 30
Answer:
C
Educational Objective: Identify hemochomatosis as a cause of hypogonadotropic hypogonadism. The paen has a clncal hstoy suspcous r hemochro matosis and should be rhe evauaed by measuring serum ransfern sauraon and errn levels. e paen has hypogonadism based on hs clincal sympoms o deceased bdo and erece dysnction, assocaed wth a ow morn ing serum tesosterone level. A hypogonadoropc eolo is ndcated by his low luenzng and lcle-smulang hormone levels. Causes of hypogonadoropic hypogonadism nclude nltatve diseases such as hemochromaoss, sar coidosis cance metasac to he putar and ymphoma. Piuiary tumors that mpa gonadoropn unction may also be a cause. s patient has several clncal ndings suggestve of possble hemochromatosis ncludng a repor of arhalgia and hepaomegay on physca examnaon. eree he next step n evaluaion of this paen's hypo gonadoropc hypogonadsm s measurement o serum fe rn evel and ransferrin satuation to evaluae r possbe hemochromaoss. e cause of hypogonadsm mus be evauaed pror o the initiaon of tesoserone replacemen esoserone heapy is stared wthou tesng r hemochromaoss the dagnoss may be missed. Although geneic disorders such as Klnefele syn drome (47XY) may cause hypogonadsm, patients wh this syndrome have hypegonadotopic hypogonadsm wih elevaed luenng and lcle-smulang hormone values unlike hs patien. Therere, kayoyping is not indcaed. A tescuar ulrasound is used to evaluae he cause of prmary esticula ilure and s no ndcaed in he eval uaon o hypogonadotopc hypogonadsm. is paent's low gonadoropin levels ndcae eher a hypohalamc or puay dsoder nsead of escular dsease. Alhough hemochromatosis may also drecly aec escular nc ton n addon o s cenral hypogonadal eec tescula ultasound s no helpul in esablshing he dagnoss of hemochromatosis as a cause o hypogonadsm. KEY POINT
• Paens wh sympoms of hypogonadoopc hypo gonadsm should have serum ransfern sauraon and erriin concenraon levels measured to denti hemochromaoss pror o iniang any heap. Biblogaphy Bacon BR, Adm PC Kowdley V et al Digosis ad mgemen of hemocromosis: 20 Pcice guideies by h e Amerc Associao he Stdy of Live Diseses. Hepoo 20:54(1):38-43 [MID 212290]
tem 31
Answer
B
Educationa Objective: Diagnose pseudohypercalcemia. s paiens ionied calcium evel should be checed Hs oal cacium level is elevaed but he is whou clea 110
symptoms associaed wh hypecalcema. Approxmaely 0% o 45% of he calcum n serum s bound o poen princpaly albumn although he physiologcally acve rm o cacium s n an ionzed (or ee) state In mos paens wh relaively normal seum albumn eves the toa calcum usually accuraey elecs the ionzed calcum fracon. However in clinical settngs whee ncreased pro en bindng of cacum may occur, he serum otal calcum level may be elevated whou a rise in he acual seum oned cacum concenraion. is may occur n paens wh hypealbuminura as may occu in hose who are seveey dehydraed and in paens wh a paraproen capable of bindng calcium (such as occasonally occurs n some paens wh mulple myeloma. is phenomenon s somemes emed pseudohypercacema or cious hypercalcema). f presen a noma onized calcum leve may ndcae tha he elevaed oa cacium leves are due to excessive proein bndng and potenay eminate the need r urhe evaluaon r hypecacema. Measung he 125-dhydoxyviamin D leve s usel n urther assessing patens wih nonparahyrod homone (PH)mediaed hypercalcema o assess r excess vita mn D producton PH testing s ndcaed n paens wih hypercalcemia to deenate between PH-medaed and nonPH-mediaed hypecalcema. e hypecacema assocated wh muple myeloma is caused prmary by umor-nduced osteocas-medaed bone esorpton due o cyoknes reeased by myeloma cels and s not PH-medaed or due to exessve vamn lev els Measurement of PH evel and 25-dhydroxyviamn levels may be indicated as pa of ths patient's evaluaon only afer rue hypercalcema has been estabshed. Parathyod hormonerelaed proen (PHrP level measuement s usefu n evauang paens wih non PH-mediaed hypercalcemia but would no be ndicaed as a next sudy n hs paen n whom pseudohypecalcema has no been excuded. KEY PON
n paens wh condons n whch ncreased po en bindng of calcum may occur such as hperal bumnema or parapotenema an arcally ee vaed oal serum calcium level must be excluded. Biblogapy lines GA Mechansms and eme of hypercalcem of mgancy Op Edocol abees Oes 01 ec;86):46 MI: 1897]
tem 32
Answer
B
Educationa Obective: Manage andogen therapy in the seing o hypogonadism Bee intating herapy r his paient wih hypogonad ism his desre for feliy should be explored. esoser one replacemen theapy can be assocated wh decreased spemaogeness and nertly. Exogenous esoserone
Answers and Critques
suppresses both ypotalamc gonadotropnreleasing ho mone and ptuitary llclestimulating hormone and luten zing hormone (LH) producton resulting in depetion of intratesticular testosterone. e eect is suppression of spermatogenesis so pronounced that testosterone replacement therapy has been studied as a mae hormonal contraceptive Based on Endocrine Socety guidelnes men with hypogo nadism should be treated wth exogenous testosterone when tey ave consistent signs and symptoms of hypogonadism and low serum testosterone levels. Symptomatic men may report reduced libido, erectile dysfunction, mood changes rritabiit tigue, or memory loss Although tis patients symptoms would likely be mproved with exogenous administration of androgen, repacement theapy may aso result in infertilty due to oligospermia. Patients wth hypogonadism wo desre fetiity may requre treatment with human coronc gonadotropin (HCG). HCG has LHlike activity and stimulates te production of intratesticuar testosterone resuting in the hgh concentrations reuired r nduction and maintenance of spermatogeness. Asymptomatic men with ow serum testosterone levels may experience decreased bone mineral density and osteoporosis. Hormone replacement therapy wil decrease te risk o osteoporosis. A bone mineral density measuement prior to the nitiaton o hormone eplacement therapy is not needed Male hypogonadism is associated with increased visceral t and nsulin esistance and hormone replacement terapy impoves tese metaboc parametes here is n o recommendation that hypogonada patients initiating hormone replacement therapy be screened r diabetes mel litus with sting plasma glucose measurement or oter testing A 200 systematic review of ypogonadal men receving testosterone therapy und no evdence of ncreased risk o prostate cancer when compared wth the pacebo/ noninterention group. e Endocrne Sociey guidelne on testosterone repacement terapy recommends a digital rec tal examination and prostatespecic antigen (PSA) level determination at 3 and 6 months lowing te intiation of replacement therap Continued regular screenng is recom mended r men older tan 40 years of age wit a baseline PSA leve greater than 6 ng/m (6 µg) Scrotal ultrasound is unnecessary prior to intiation of testosterone therapy; a clnica testicular examination to ule out abnormaities or a testicular mass is sucient KEY POINT
• ror to initiaton of testosterone terapy r hypogonadism te desire r fertility sould be ascer taned because exogenous testosterone replacement terapy may result in oligospermia and infertili. Bibliography Samplasi MK. Loa Y Wo ng K, Lo KC Gober ED Ja KA Testoserone use n the mae nfery popuaton: pescrbng paes and eects on semen a hoona pameers Ferti te 2014 an01():64-9 [PMI: 209]
Item 33
Answer:
C
D
Educaional Objectve: Diagnoe thyoid storm.
'! 1 1 . t 1 os n n · : ue g e e je n o Te eo o e e \ T ( g eu g n n p �e ee p n n e onte t o e e n e l I n e et t t pe ot e a ep b d s n ue p t g t s h i nn a p pn 1
KY PON
• n patients with underying Graves disease tyrod storm may be precipitated by te iodine content und in contrast media. Bibliography KlboGwiezznska Waosy L ho emegences Me in Norh m 02 M96(2:385-0 PM: 22443982
e 34
Answer
D
ducaional Obectve Manage postsgical hypoparahyrodsm
his paent wthout parathyod function should be advsed to decrease s calcum supplementation ntake. n patients without parathyoid unction, stimulation of the kidney to convert 25hydroxyvitamin D (from the liver) nto te active 111
Answers and Citiques
form, 25- dhydroxyvtamn D (calcitrol) s lost as is the sgnal o nse reabsorpton of calcum n the kdney n the dstal convoluted ubule and oop of Hene. As a resut both cactriol and calcum suppementaton must be pr�d as was done n ths patent However wthout reabsorpon o cacum by the kdne oal cacium wl be absobed and passed through the kdney, resultng n hghe levels o urine calcum than n patients wth norma parathyrod hormone eves. In montorng calcum status n hypoparathyod patients the recommended goal shoud be a 24hour urne calcum leve o less than 300 mg/24 hours (75 mmol/24 h) wth a concomitan serum calcum level in he low normal ange (8.08.5 mg/dL [2.02 mmol!]). f the une cacum evels are supassed t s approprae to decrease the calcium intake rst; in patens wth serum calcium levels greater than 8.5 mg/dL (2 mmolL) and urine calcum greate than 300 mg/24 hos ( mmol/2 h) concurrent decreases n boh calcum supplementation and calctro are ndcated. Athough 25hydroxyvitamn D levels are the best ind cator o tota body vamn D stores n patents wth normal paahyroid unction, would not be helpful r herapeutc decisonmakng n hs patent as he lack of PTH requres treatmen wth actvated (125dhydroxy) vtamn D. In hs paten 25dhydroxyvtain D evels measured concur rently wth the serum and urne calcum leves are he most appoprate ndcators o therapeutc eect. Remova o the parathyrod glands does not alow the PT leve o be used to monitor appropateness o therapy It would be expected to be ow o undetecable n ths patent who has had esecton of hs parathyrod glands and chemo herapy and radation It woud be napproprate o contnue the curren egimen gven the elevated 24hour urne calcum levels Pesstenty elevated levels coud lead to nephrothasis o nephrocalcnoss. KEY POINT
• he urne and serum calcu goas are derent n patients with hypoparathyrodsm the urne cacum goal s ess than 300 mg/24 hours (75 mmo/24 h) and serum calcum goal s between 8.0 and 85 g/dL (22. mmo) n these patents Bblography
rapdactng nsuln beore ntensve exercse Snce the dua ton of acion o nsuln glulsne can exend up to 4 hours cov eng the meal consumption prio to exercse wth a smaler dose of nsulin glulsine can educe the rsk o hypoglycemia n the seing o ntense or prolonged execse Dscontnuaton o nsuln glargne n a patent wth type diabetes wl ead to hyperglycemia i the rapdacting nsulin sn't adjusted to provde basa nsulin coverage he hypergycema and nsuln decency that develop n the absence o basal nsuln couped wth the stress assocated wth exercse wl lead to an ncrease n he release of coun terregulatory homones In this scenaio there may no be sucient nsuln o decease lpolyss and subsequen oxidaton of free ty acds his could ead to diabetc keoacdoss. he mealtme isuln prior to exercise should be decreased however modcaion o he det wth ncrease n carbohydrates, aher than protein can also hep avod exercseinduced hypoglycemia Consumpton o 5 to 30 gams of cabohydrates pror to exercise and/or a snack with complex carbohydrates afte prolonged execse can help mtgate the rsk o hypogycea Cabohydrates especialy smple ones, can rapdly provde glucose to he boodstream and maxme glycogen soes n the liver hat can be uil ed r uel duing exercse. he dgestion time proten s proonged compared with cabohydrates thus povding a sower source o ener durng exercse A sldngscale regmen o insulin glulsine is a reacve management pan gucose conrol. In ths scenaro t is possbe tha the patien could have an increased rsk of hyperglycema or hypoglycema pror to duing or aer exercse secondary to nsucent or excessve doses o insu ln rom the sldng-scale egmen KEY PON
Because exercse can ncrease gucose utlaton by the musces reducng the doses o mealtme nsuln n a paient wth dabetes elis w decrease the rsk of hypoglycema wth ntense or proonged exercse Bibography Ameran Diabtes Association () Fondations o cae ecaton nur tion phsical actvi, smong essation pschosoca ca and im nzaon In Standas o Mdial Cae in aees-05 ias ar 2015 Jan3 Sp S030 M 25537702
Khan MS. Waguespack SG H M Mdial managemnt of ostsrgca hyoarahoism Endocr Pact 201 Ma -Ap:7 Sppl 118-25 [M 11347]
em 36 Item 35
Answer:
A
Educational Objective: Manage execise-induced hypoglycemia.
s patent should decrease hs mealtime nsuin glulsne dose pror to exercse and connue his nsun glargne. Exer cse ca ncrease gucose utiizaon by the musces whch can nduce hypogycemia n the setng of exogenous nsuln. hs patient consumes a meal and admnsters insuln gusne a 112
Aswe
A
Educatonal Objective Diagnose central hypothyoidism
Measurement o the serum ee thyroxne (T evel s the most approprate next step n management r ths patent who has clnca evidence o hypothyrodsm (tgue con stipaton cold intolerance dry skin, delayed relexes, ane ma and md hyponatrea) bu has had radaton to he base o the skull ncludng he ptutary gland Although measurement of thyrodstmulatng homone (SH) s the
Answers and Critiques
most accurae relecion of hyroid saus in paiens wh an inac hypohalac-piuiary-hyroid hypohalac-piuiary-hyroid axis, i is not a reiable measure of hyroid function in paiens n whom here is loss of hypohalamic-piuiay functon such as seen in his paien. His low-normal TSH in he conex of clincal hypo hyroidism suggess possible central hypohyroidism, and measuremen of he circulatng leve of hyrod hormone he ee serum T 4, would herere be a more accurae ndicaion of his hyroid saus. Repeatng he TSH measuremen would no be appro priae in his paien wh signs and sympoms of hypohy roidism, as unreaed hypohyroidism eads o increased cardiovascular morbidiy and morali. In additon, because of likely cenral hypohyroidism, the TSH level woud remain an inaccurae ndicator of thyroid funcion. yroid scingraphy s unlikely o distinguish the source of he hypohyroidism, as paiens wih primary or secondary hypohyrodism have decreased radioacive upake. yroid scanning is mos helpul in eucidaing he cause of hyper thyroidism thyroidism Ultrasound of he neck is normal in paiens wih cen ral hypehyroidism and would be unikely o provde any addiional inrmaion abou his patien's hyroid saus
KEY PONT
• Measuremen of 24hour urine calcium and creatinine creatin ine leves wil disinguish disinguish beween pr imary hyperparahyroidism and milial hypocalciuric hypercalcemia. Bibliography
KEY POINT
• When cena hypothroidism is suspeced, measure men of he seum ee hroxine (T 4) level is essenial. Bibliography Persani L Clnical eview: Cenal hypothydism: pahogeni, dagnosc, nd hepeic chalenges . J Clin Endocrino Meab 202Se;7(9):3068 8. [PMID 2285142]
Item 37
rarely associaed wh hypercacemia and herere does no require heapy o lower seum cacium evels. Screening other mily members r he disorder is indicaed. Bone densiomery is not indicaed in his age group in he absence of fagiiy actures or oher risk cor s such as ong -erm high-dose glucocoricoid glucocoricoid use or primary hyper parahyoidism. A parahyroid sesamb scan is a very usel nuclear imaging sudy r localizaion of o f adenomas in patens wih primay hyperparahyrodism or parathyroid cancer. How How ever primary hyperparathyroidism has no been conrmed in this paient wih suspcon r FHH making ths sudy premaure. e need r surgical reatmen rea tmen in his paien has also not been esabished. esabished. herere surgical referra r parathy roidecomy would no be appropriae.
Answer:
B
Educatonal Objectve: Dagnose famia hypocalciuc hypecacema.
is paen's urine calcium and creainne levels shoud be measured. Her laboraory values are conssen wih hyper calcemia, and her parahyrod hormone level s oward he upper end of he normal range. n her age goup and wh a mily member wih a suspicous hisoy, is impoan o disinguish beween primay hyperpaahyrodism and miial hypocalciuric hypercalcemia (FHH. he disinc ion beeen primary hyperparahyroidism and FHH can be made by a 24-hour urne collecion r calcum and cre ainine which wl esab esablish lish he amoun of kidney calcum excreon and wil alow evaluaton of he calciumcrea nine raio. Toa urine calcum of less han 200 mg/24 h (5 mmol/24 h and a cacium-creainne cacium-creainne ratio less han 0.01 are hihly susiv of milal hypocalciuric hypercalcema FHH results om a muaion n a specic calcium-sens ing receptor in he parahyroids and kidneys and resuls in an upward shi in he range of calcum and PTH leadng o these clinical ndings. Alhough a rare ent, makng his diagnosis is cucia because i may preven unnecessary parahyroidecomy r he paient. e course of FHH is
Shinall MC J, Dah KM Booe T Deeniaing ilial hypocalcic hypecaceia fom riary hyperparhyrodis Endocr Pr 203 JulAg4)60 [PMID: 345644
Item 38
Answer
D
Educatonal Obective Evauate timng of pranda nsuln n a patent with dabetes meltus
e mismach of iming of insuln aminisration o od ntake wh meals possibly relaed to he me demands of her new job, is he mos ikey explanaion r he erraic glycec luctuations noed on his paiens blood glucose og e adequacy of her nocurnal longacng insuln s releced in her near-goal pre-breast blood glucose levels. However, he major luctuaons occurring around mealimes are bes expained by nconsisent use of her immediaeac ng insulin relave o od inake. Meal coverage wih insuln should mimic he physiologc paern seen wih endogenous nsulin secreed om pancreatic bea cells Adminisaion of mmediate-acting insulns should herere ideally occur jus prior o or a he time of he meal consumpion consumpion Because of he rapid onse of action wih hese agens shiing he im ing of admnisaion awa awayy om hs physiologic paern may result in he bood gucose lucuaions seen in his paien An impotan aspec of o f dabees educaion is helping paiens paien s understand the acions of heir prescribed insuln regimen and the impoance of imn issues when using hem. hem . Anibodies can develop in response o exposure o exogenous insulin; however, these anibodies are rarely clinically signican and woud no adequaely explain he blood glucose patern seen n hs paien. Gasroparesis can cause erraic blood glucose values due o eher rapid ransi or delayed empying of od wihn he 13
Answers and Critques
he bone lesions o multiple myeoma are primarily osteolytic, in which case urher evaluation r hat diagnosis with a serum and urine proein electrophoresis would be appropriate. However his patien's radiographic ndings are not consistent wth a diagnosis of multiple myeloma and rther evaluation r this disorder would therere not be indicaed indicaed.. Most patiens with Paget disease of bone are asymptomatic and are identied ony by eevated serum akaline phosphatase levels detected on laboratoy studies obtained r other reasons. In many patients wih mild disease clinical obsevation wihout initiation initiation of therapy is appropriae However in this patient with symptomatic disease in a critical weightbearing skeleta area cinical obsevaion without treatment woud no be appropriate KEY POINT
• Treamen of Paget disease of bone with antiresorptive antiresorptive agents is indicated in symptomatic patients those with elevated calcium levels or patients patien ts with involve ment of skeletal areas at high risk of complications including actures. Biblography
KY PONT
• On conrmation conrmation o pregnancy in a patient taking levothyroxine serum thyroidstimulating hormone should be checked to determine the need r levothyroxine dose adjusment Bbliography Sagao- Gree A Aaovich \ Aexaner e a America Tyo SagaoAssocaion Taskre on Trod Disease Dug regnancy ad ostparm Gdelnes of e Amecan yo Assocato o te diagnosis ad anageen of yo disease g regnancy and osatu Tyroid 20 Oc2008-25 [MI 2787128
Iem 42
Raston SH Page's disease ofte oft e bone. N Engl J Me 2013 Feb 4:368(7) 6650 [M 230029]
Item 41
proteins protein s he increased thyroid hormone requiremens of the fetus also contribute o this change in serum T levels. In this paient with a serum TSH TS H value above 2.5 µU/mL (25 mU/L) during he rst trimester he dose of levothyroxine needs to be increased rather than decreased or discontinued he serum TSH level should be rechecked in weeks to ensure that the dose adjusment coninues o be adequate. Likewise yroid function tests shoud be repeaed a east once during each trimester to ensre that additional adjustments in he evothyroxine evothyroxine dose are not needed.
Answer:
D
Educational Objectve: Teat hypothyoidsm in pregancy.
is pregnant patien's levothyroine dose shold be increased to ower he serum thyroidsimulating hormone. aternal thyoid hormone production typicaly increases by 30% to 50% during pregnancy; therere, in pregnant patients patients requiring levothyroxine supplementaion the replacemen dose usually needs to be increased to provide adequate thy roxine (T4) r the neuologic developmen o the fets. e combination of this patient's elevaed thyroidstimuating hormone (TSH level and low total 1 level sugges that her levothyroxine dose should be increased. During pregnanc the physioogic changes in thyroid hormone levels include a reduction in the seum TSH leve and an increase in the serum toal T1 level his change in the serm TSH level is paly due to he rise in the serum human chorionic chorionic gonadotropin gonadotropin (HCG) level both hormones share sequence homolo in their subuni. s the serum HCG H CG level rises with progression progression o pregnanc the hormone can bind to the TS ecepors reslting in a reduction in serum TSH levels. Consequently, the normal reference range for serum TSH during pregnancy shis to a ower vaue rom o U/m m/} prepregnancy to 0.03 to 2.5 µU/mL (0032 mU/) during the rst trimeser dditionall the serum total T 4 level rises ld above the normal nonpregnant reference range. Par of this increase is due to the higher leves of estrogen associated wih pregnanc which cause an increase in serm total protein levels, incuding serum thyoid hormonebinding
Ans An swer wer
B
Educational Objecte Objecte Dagnose the cause of adrenal faure
ti l ll n Wh nl e e l l A l l R h h h n n B n n l : i A z 6 6 8 n \ A e t e l y n 15
Answers and Critiques
C CONT.
h 1 o o o op mc o ow o hpoooop hpooa m poi oo o eo e e ·1e o o v ho ope (ooo) o e o poopve p o y h pohmp pooop hpoo wo o o pe wh hpm e eooo e o p pop om e hmoh o h p m e c hoh h p mh o oo he oe o hve hh o v e whh omo p popex Be py pope e o wo o e h ypeem KEY POINT
• Patients it biateral adrenal errage tyically resent wit clinical features f acute crtisl and aldsene decienc, including gastrintestinal disturbance, letar eakness ytensin, sck, yglyceia and electlyte ibalances suc as ynatreia and yerkaleia
Measurng 24u urie fee caeclamine a eta nerine levels uld be used t screen r hechrcyma. If tis aent ad an adrena adena, se ud certainly need be screened ecrcyta rir t sgery but se des n ave a knon adrenal lesin Her syts and crbidities are exlaned by er diagnsis f Cushing disease ad se as n secic signs r syts that reuire a evauati r ecrcyta. A PET scan is nt necessay or indcated in te evaluatn f Cusng syndre Cusng disease is caused by a tuitary adena and is nt aignant. Cu sing synde due t ectc ACTH ductin s ften caused by a cancer. PET scan ay be indicated t ty t lcalize e surce f ectic ACTH, but te surce f te excessive ACTH is aready kn t be f a ituitary adena KEY POINT
• Paients ith yerctislis suld have a screening dualener xray absotiey scan because tey are at a igh risk f sterss and acture Bblography Neman LK le BMK Fnng JW t a Th dagnoss o Cusng' yn om: an Enocrn Socty clncal pactce gudlne Cl Enocrnol Metab 2008 May9(5526-0 MID: 18480
Bibography Rosenberge LH. Smth PW, Sawyr G et a Blateral adrenal mohag: the urcognizd cas ofemoynamc colap aocatd wh hpa n-uc thromocyopena Crt Car Md 20 Apr;39(4)8338 [MI: 2122799]
Item 43
Answer:
C
Educational Objective: Evauate a patient with a new diagnosis of hypecoisoism for osteopoosis.
is atie ith ely diagnsed yercrtisis s at ig risk r stess and acture, ad a screening dualene xay absietry DEXA scan is indicated. e ecanis f stesis n ates wi Cusing synde is reated t deceased intestnal calciu abs tin decreased bne rain, iceased bne restn and decreased enal calcu reabsin Patients ith l be densty shuld be cnsdered r bissnae teatent t reduce the risk f acture. A 8 dexaehasne suressin est can be used t el lcaize e surce f adrencortictric rne ACTH i a atient it Cusing syndre. Paients it with a suessed ctisl level In caisn aents it ecic ACTH rductin d nt esnd t 8 f dexaehasne and ther crtisl levels reai elevated. Hever, this test assciated wit a nuber f lsesitive results. e 8g dexaetase suressin test is nt indicated r tis atient because se has already ad a e denitive test ntraersal sinus salig has bete sesitivity and secicty en ceted by a skiled iner veinal radoogist. 116
Iem 44
Answer:
D
Educational Obective Manage pimary adenal faiure
he mo ppope me h oe me o h pe' pmr e wo e p eoe 5 m o y ocoo 005 m oe pm e e here e he po o he homoe o he re oe ae heore q oh ooro a meooco ree Bee he o oe phoo epceme o ppopte oe p h coco o v h 5 m e oe a phoo epme oe o on o e m ee oce a obo wh uoooe whh h mo pe meraococo popee hoo peme oe o oooe re 5 o 2 m pe a eehsoe pma a ooo co e e he ooo poo o comto epeme herp wh a meococo ch oooe. oweve mehoe aoe wo o ppope hep pm aeal e e o Focooe oe ao pprope e wo o pove oco epcem ocooe h bo cooo mocoo ppe wh pm ooo c phyoo epeme ose o 2 o 2 wo o hee e oe o oe ove 50 m hy oe h eqe eoo o o ow o e s mooheap oweve eme wh hoooe 0 m hee me oe o pvde
C
Answers and Critiques
C uphysg u gucc cud e u p ue
CONT
tgec Cushg yde f d g te s ets wth y u qu guccc m pysgc s e ess upp epy ct u gey ude c ee yc e f yct qu) te ss e ug w g s s) uuy 45 75 g/y j j ge u c es u 5 g/ y gdu pe fw u h
KEY PONT
Primay thyroid ymphoma most oten occurs in elerly wome with underlying hypothyroidism; the typical presentation includes rapidy enlarging goiter weigh loss and night sweats, and imaging reveals a difusely enlarge thyroid. Bibliography i HC an Kim t al Pmary hyr lyma CT fng E Ral 003 n;46(3):33-9 [MI: 27587
KEY POINT
• Patients with prima adrenal iure reuire both gucocorticoid and mineraocorcoid replacement in physiologic doses.
Item 46
Answer
E
Educatona Oective Treat primary hyperparathyroidism d concomitant vitamin D deficency
Bibliography Nea Nieman L Adrenal insucicy: ol, agn an tatme C Opn Ecr Dab Obe. 201 Jn17(3)217-23PMID 235886]
Item 45
C ae ypcaly a patchy intrate wth minima lymphade opathy Tis pent's image reveals mae iuse enarge met of the thyoi ad she dd no have a history of prior iness
Answer:
C
Edcatonal Objectve: Dagnose prmary thyrod ymphoma. he patet has prmay thyroi ymphoma which ost oen occurs eey women with a ong-sanding histoy of Hashimoto thyroiits Te cnica pesentatio s ypicaly oe of api onset (weeks) of an eargig goter with wegh loss and nigh sweas. The iagosis is ade by bopsy of the thyroid wth ow comety. reatment typicaly ivoves chemotherapy and/or radiaion herapy Tyroidectoy s usualy no eee. C scn of the neck, athe tha ultasound was orere in ths paet because f he compressve syp toms an positiona breathing issues C sca aows visua zati of he eaged thyro gla ad assessmen of he patecy of the achea In this image, the "doughnut sig can be seen whereby he enlarge thyro extends behid an competely encicles he trachea New-onset Graves isease s uey to occur n a patient of this age patculaly with her og-stading his tory of hypothyoidism Futhermre there is no bi or oher cinica sig of Graves isease ad he hyroegaly associae with Gaves isease s no acute n oset This pae is unkey to have papilary hyrod cance, as these tuors ypicay gow vey slwly i cotas to u g , is tpcay diusely earged as see on this C scan Rathe a stict noule and poeially cocomiant cevi ca lymphaenopathy woud be epected Subacute (e Quervain) thyroitis is assocated with acute onset of anterior neck pain. t is picaly seen low ig a vira iness in the preceng mohs. The changes on
e mst apprpiae reatment of hs patent s t replete his vtamin deciecy with a supplement such as viamin D 3 (chlecalcifeo) He hs pimay hypepaathyoidism as shown by hs elevated seum calcium an parahyoi hor moe leves Hwever, thee is a hgh pevalence f cocurrent vtami D eciency and insucency in paiets with pi ry hypepaahyrois an ow levels of 25-hydoxyvi tam ca smulate paahyri hrme secretion in -adenoatous glnds. Because of his measurement of viain evels shou be orered as part of the evauaton of pimay hyperparathyrosm and repleion should be po vided if ietied. In these patets, it is portat to eplace her vitami D o a level of at east 30 ngdL (5 no/L) Ae this level is eached the patient shoul be paced on a viamin D osage to maina tht vaue. The choice to use chlecalcifeo versus ergocalciro is oten based on the level of vtami D eciec. Since egocacifeol is more readily available i he 50000 U r ad has a shorte haf-ife, t s recommee when a patient's vtami D level is ess tha 0 gmL (25 nmo/L) Cholecacifero is oten used whe he evel is between 0 a 30 ng/mL (50-5 nmol/L) or r manenance. Sice this paiet aeady has hypercalcemia a owdose epetion is esired the ower oses (00 aily) of vitamin D3 (ver-the-counter cholecalcierol) shoul be used. Tis patients seum cacum shou be moniore at east monhly This paient oes ot meet the threshod r surgey. His serum tta cacium eve is less than 1 stanr eviation fom upper limit of norma his bone ensity score s not in the osteoporotic or tretment range he s oler than O years g, gu pv. Aedonate woud be a excele optio clcium eucto ad simultaneus eatmen of osteoporosis if his scoes wee lowe o Fract ure Risk Assessment oo (FRAX) scores were highe Te FRAX calculator ees the 10-year acture risk r patients wth scores in the - O to 2 range. e FRAX calcuator (wwsheac.ukFRAX) 17
Answers and Citiques
ncorporates muple risk ctors includng sex fracture hisoy femoral neck bone neal dens, steroid usage smoking, BM! age, and acohol ntake to deerne pojeced facture risk f the risk o maor osteoporotic fracture is greaer tha or equal to 2% o te risk o hip acture is greater tha or equal to 3%, the patients benet from therapy exceeds the ik and treatment should be oeed. Calcitonin is an option r reducing his calciu leves, bt he is currenly asypomatic and does not waan calcium loweng Ciacalce, a calcimimetic agent, is another option r lowering calciu r sympomatic patients with kidney invoveent is patien has peseved kidey unction and no ymptoms Due to the cos and poena side eects of cinacalce i would not be indcaed at ths me KEY POINT
• n patients with piay hperparathyroidism and concomitant vitamn D decienc 25hydrovitai D leves should be repleted to at least 3 ngdL (7 nolL) o prevent ther pararoid hormone stmuation.
Bibography Holck MF, Binkley N. Bischo errai HA, Godo C any D. Heaey R Wave C Evauatio tamn ad pvio of vian D dfciecy : an Edocri Socty clinica pracice guidelne J Ci ndocnol Mta 201 Jl;96(7)19-30 [PMlD 2646368]
Item 47
Answer:
A
Educational Objective: Manage diabetes meitus in a hospitalized patient. e t ' wl z wi l l i i yly e w m i i f Cal Elg g t ICU el l 140 m/ l) l 80 / 10 l C Py t 0 m/ l/) ee yy oll li O n y ey J G ly li i t oi . y w le e l W iied e c fi wi I y a y R e e l a l
118
o tle nd glc vels te . Sl l yoogi u c l lel Sil il me o nu ey l g KY POIN
• For noncritically ill hospitalied patients with diabetes mellius and hypeglycemia a weightbased treatment plan that includes basal and pandial insulin i recomended
Bblography Amcan Dies Assocaio (3 Diabts ca th hospta nusig hom ad slld rsing city I Sadads o Mdcal Car i Diees205. Dias Ca 205 an38 SupplS80 PMD: 25535]
tem 48
Answe
B
Educationa Objective Diagnose ushing syndome e most appopiate next diagnstc test hs patien is the g dexamehasone suppession test She has e typcal clinical features and ndings of cortiso excess o Cushng syndome. he mos common cause of Cushing syndrome is exogeeous gucocoticod use; however she ha no receved glucocoticoids To evauate for Cshig syndroe biocheical evidence o hypercortsolsm ust be conred by use of severa screening tests hree screenng tess ae used r Ching syndroe: the g dexaehasone suppression es given late at nght with assessent o cortso suppression the next orning), 2hour rne ee cortisol excretion (o quanti otal daiy cotisol secretion) and easueent of evening saivary cortisol which nomaly reaches a nadr at that tme but remains eevated in paients wth Cushing syndroe). A east two abnomal rstline screening ests are requred r diagnosis nly ae establshing bocheical hypercoisois should he source of excess c otisol prducton be ought Measuremen of adrenocorcotropic homone (ACTH) is not a screenng test r Cushing syndrome Aer documenation of excess cortisol production ACTH levels ay be useful n deterning if hypercortisolis is ACTHdependent or ndependen howeve, i is no an appropriate initial screening tes An 8mg dexamethasone suppression test is helpu in dag w uhg da (piuiay mor seceting ACTH and ectopic ACTH production However it i not a sceening test r Cshing syndrome and would be approprae only in specic situatons ater Cushing syn drome s diagnosed. A piuitay M hould be odered only aft er hypecor iolsm and Cushng syndome are diagnosed ad a pituiay adeoa s suspeced as a case Measurement of serum cortisol levels lacks sensitivity and specicy diagosng Cushig syndrome, prialy
Answers and Critiques
due to the pulsatile natue of coisol secetion, and s not used as a sceenng test. KEY POINT
• To sceen Cushing syndome biochemical evi dence of hypecotsolism must be confimed b y a 1-mg dexamethasone suppession test 24hou une ee cotisol tesing and/o measuement of evening salvay cotiso levels. Bibliography Nima LK Bie BMK, Fnding JW l a Th dagnosis or· Cusings sy d: A Edocine Socety cinca pcic gde. i Endocio Mtab 2008 May;93(5)526- 40 [PMI: 1833580]
Item 49
Answer:
A
Edcational Objective: Treat an obese patient with type 2 diabetes melitus wit bariatric srgery.
Patients with a BM! between 35 and 40 with one or more complicatons associated with obesity should be con sideed baiatric sugey with the goal of sgncant weight loss and mpovement in meabolic abnormai ties. is obese patient has type 2 diabetes mellitus wth advanced micovascua disease along with othe compli cations associated wth obesity incuding hypetension hypeipidemia, obstuctive seep apnea gastoesophagea acid eux disease and osteoathitis. His attempts at life style management wth diet and exercse did not esut in weigh oss tha substantiay impoved his meabolic abnormalities o obesity Inceasing the insulin doses coud potenially exac ebate the weekly hypoglycemic events occuing in a patient wih hypoglycemic unawaeness. is could also lead to more weight gain due o equen treatments o hypogycemia Mermin is containdcated in men with a sem ceatinine level above 15 mgdL (32.6 µmolL due to the possibiliy of lactic acidosis and wil not add ess the unde lying poblem of obesity. amlintde slows gastic empting which can decease appetite. he weight loss associated with the use of pramin tide is modest and it may not be sucient to impove the metabolic abnormaities and obesityelated complications in hs patient. In additon, he patient's hypogycemia may be exacerbated by pamlinide. KEY PONT
• Obese pesons M between 35 and 40) with type 2 diabetes melius and associated complications should be consideed baiatic suge Bibliography Mcanck Yudm A, os DB el a nica acc gudis t piopive nutiona eaboic and onsgica suppot f baatc sgy pain-203 pda cosponsod by A mca Associaion inica ndocogsl s e Oesty Scity ad Amica Sociy Mac & Baiatic gy dc Pact 2013 Ma - Ap9(2 3 37- 72 PMD 23529351
Item 50
Answer
D
Educationa Objective Diagnose an incidentally noted adrena mass.
e mos appopate next step in management is to evalu ae pheochromocytoma pefeably by measuement of plasma ee meanephines in his paient. Appoximately 10% to 5% o incidentaly discoveed adenal masses ae nctiona although most have no ovet clinica manifesta tions eee al patiets wih an ncidenaly noted adre nal mass should be evauaed the autonomous secetion o cotiso and caecholamines and those with hypetension should also undego testing pimay hyperaldosteonism. e lowdose dexamethasone suppesson test should be perrmed to evaluate subclnical Cushing syndome given its supeior sensiivity compaed wih othe sceen ing tests 24hou uine ree cotiso and latenigh salivay cosol; ths test was negative n this patien Measuement of 24hou une metanephines and catecholamines is the usual st test in most asymptomatic patients to evaluate r catecholamine hypesecetion alhough n hose with imaging suggestive of pheochomocytoma measuement of pasma fee metanephies is the pefered study because of its vey hgh sensitivit and high negaive predictive value a normal stud maging in this paient reveals a wellcicum scibed patialy cystic lesion with high attenuation on non contrast CT scan, which is in keeping with a pheochomocy toma and is not pcal of an adenococal adenoma which characeisically has low attenuaton on CT scan (density <0 ounseld units due to elatively high lpid content. Management of an adena incidentaoma depends on ts size maging chaactestics (phenotype and ho monal functioning Almost all adenal tumos ha are overtly functiona are lage han 6 cm n sie o have un voable imaging chaacteistics should be consideed sugical remova oweve, biopsy o sugcal esection of any adenal mass prio to uin g out a pheochomocytoma is not recommended as any manipuation of a catechol aminesecreting umo wthout appropiae peopeative management can pecipitate a hypetensive csis Measurement o the plasma adosteone to plasma enin atio is indicated as pa of the evaluaion of an incidentally discovered adenal mass in a patient with hypetension, but no in this indvdual who has nomal blood pessue. Not peming additional tesng may miss a subclin ical pheochomocytoma and would theee not be an appopiate next step in management. KEY PONT
• A patien wih an incidentally noted adenal mass shoud undego biochemical testing subclinical Cushing syndome and pheochomocyoma and those with hypeension should aso be evaluad pmay hypealdosteonism Bibliography Anad G Boscao M Adna cdeaoma Bs Pac Rs in ndc Metab 202 26405-19 [PMD: 2286338] 119
Answers and Citques
Answer:
Item 51
D
Educational Objectve: Manage the imtations of hemogobin A 1 measurements n a patient with dabetes metus and chronc kidney disease.
is patent should measure hs postprandia gucose evel e hemogobin A measurement is not aways reiabe in the seing of chronic kidney disease; thus ngerstick bood gu cose measurements shoud be cosely evauated hep guide therapy. Ts patient's sighy eevated sing and premeal bood glucose values may be ndicative of postprandia hye gycemia that could be detected with posrandia gucose measuements and used to guide therap For patients trying to achieve hemoglobin A levels ess than 70%, sting and premea glucose targets usuay are set at appxmaely 80 to 130 mg/dL (4-2 mmo) Tis patiens sighty out of nge sting and premea glucose measurements seem at odds wth the ecent drop in his hemogobn A eve to 62% Specic scenarios unique to endstage dney dsease can aect the accucy of the hemogobin A measuemen Hemogobin A can be sey eevated in the setting of chronic dney disease due to carbamylated hemogobn seconday to uemia inte erng with some of the assays emogobin A can be sely decreased in he seting of a educed ethocyte iespan iron decienc, blood ranssions and increased ethropoiesis ih ethropoiein use In ths patient the gerstc bood glucose measurements do not correae with the most recent hemogobin A aer niaion of eythropoietin e hemo globin A vaue is sely decreased ater eyhopoiein ther apy as a result o a change n he proporton of young and od eryhrocytes and a change in the rae of gycation. Te paents ngerstick bood gucose vaes ae ee vated which further increases ris r mcovascuar and macrovascuar damage e current regmen shoud be adjusted o decrease hypegycemia. Deceasing he insuin detemi dose woud ncrease hypeglycema based on daiy bood gucose data provided by the paient Dscontinuation of he pepndia insuin guisie based on the lsey decreased hemogobi A eve woud increase the hypergycemia noted in the ngerstick bood gucose values 1
1
1
1
1
1e
1
1
1
KY PINT
• End-stage idney disease in patiens wh diabetes me tus can aect the accuracy of the hemogobin A eas urement which shoud not be used to guide therap 1
Bibliogaphy Ng JM. Coke M. Bhandari S e1 a Te eec f n nd erythrpetn teament n e Al pens w dbete nd crnc dney dsese Dbetes ae 200 v:33()230-3 [PMI 298337 Item 52
Answer:
A
Educationa Obective Diagnose an androgen-pro ducng adenal tumor
e most appropiate dagnostic tes o perrm next is an abdomina C scan to conrm he dagnosis of an 120
andogenproducing adena umo Appoximatey 50% of andogenprducing adrenal tumors are benign adenomas whle the other haf ae maignant Symptoms ae usuay mnima or absen in adut men. Women typicaly pesent with apidy progressve signs and sympoms o androgen excess, incuding acne hirsutism, and vrilization (deepening of the voice, ctoromegay, and mae-patte har Joss) and may also have irreguar menses n patients wth cinca evi dence of hypeandgenism biochemca esting is peromed pior to imaging and should incude measurement of sem testoseone and dehydroepiandrosteone sue (DHEAS), an adrenal androgen. s patient's bochemica evauation has revealed mared eevaion of DHAS and mld eeva tion o testosterone, mang an androgenproducng adena tumor the mos liey diagnoss DHEAS eves above 8 µgmL (216 µmoL) are diagnostic of an androgen-producing adre na tumor e elevaed serum tesoseone evel seen in his patent is iely a consequence of the periphera metaboism of adenal androgens to testosterone The seum testoserone leve would be more than 150 to 200 ng dL (526.9 nmo) n the seting o an androgen-producing ovaran tumo Perrming a owdose dexamethasone suppression test or pituiary MR s not indicated because Cushing syndrome is uney with a normal 24hour urine ee cortiso eve and in the absence of specic features of hypercortisolism (cial pethora voaceous stiae, and supracavicula o dorsocervca t pads) evic ulasound is not an appropriate iniia imag ing test because the mared eevation of DHEAS maes an androgenpoducing adrena tumo much moe ikey han an ovarian neopasm Athough the patient has a mily hisoy of poycystic ovary syndome (PCOS), the tempo and severity of her cinica presentation are no in eeping with ths disorder Athough adrenal androgen excess occurs n 30% to 40% of women wth PCOS ony a mid elevation of DHEAS (3 µg mL [81 µmo]) is expeced KY PN
n femae patients signs o andogen excess such as pogressive hirsutism and viiization ove a short period of time suggest the diagnosis of an androgen poducing adena o ovaian tumor h aan , hn N Grsman A Anden and esgensecreng adena cnes Semn Onc 00 ec6)63848 M l638]
tem 53
Answer:
A
Educationa Obectve: Manage diabetes meltus with coninuous glucose montoing
ere s a discrepancy between this paient's ngestic bood gucose vaues and her hemogobin A vaues that can be qucly reconcied wth a 72-hou continuous bood gucose monitorng sysem Continuous bood gucose monitoring sysems use an elecrochemca enzymatc sensor to mea sue the gucose content of intesiia uid via insertion o 1
Answers and Citques
a ubcneo neele. n ome ytem ata ecoding cn ae avilble in real ti to h atin whees ohe model se e d o le cces nd aysi. Sin h does o ve kiney see or anei t cod ae e ccuac of emoobn A esues s lkely as pisd o hyprgycemia n ded by crent motorin s. Fingrtick bloo glcose aes onl ode a smal snpho of e cose vaiaty hat occ thou e da. Undeced yeglyemi o hyma ca ed sgca deeces eween h ngerstk blo glco aus a h xpctd hmolbi A level. He wd ange of tn boo glcoe vales old b indiatv ofdeecd rig hpogyma. Itrmttt connu o glcose moong s reommne we otandia erglyemia d pheon r vngh hypoglycema s. Leyl modcons re rcomd glycc mee; owev, bcse s t xcses n vnng ovnght hyoglce hould cons a vluat wth nous glcos monn. ddtl exi a xac th ypoglycmi. patin do o h nc o postd yerglycm on ngestck bood go ar mens hogh i co b ise s n ma f he als pedal Gven th dispacy i h bod gucos vlues d A evel ypoglya hold b rul out s ncasig h inl doe t may ease th rsk f yoglcem.
rmna ai gowh wll lowed wi combd oa contatv s. Oral ontacepies ha ontn 30 to 35 µg of etiy esaio pe to e oe eecive i mngig hirim tha muation contnng ess ehnyl esrdol x onhs of eaen s cosdeed e inimal nev in whh dtri th l o rons. dhrnc to an oral conracte gin wi ovde s paten redcal a w a crac bnt n addon e ris o ndomtia hypplasa s dish ntrmttt ogto withdrawal, alu eecv dcasg t s o endmeta hypplaia wold v o eet o thi pat's concn rrng um Th vonoges itraui tm a lon cg, sib conacpti eve hat mnses logtm k of dotl ypelasia pit with PCOS hwe t p t him an s ec o adoen oducon. Spooao i a poet antinoge d is very etive agait lpan hss n pes wth POS Howee os nt contro of he mensta cyce Whe spionoatn i pr patient sho be coeed gaig th ttia taoncity i l ts an a coce eable coneptv mtho hol sh o pvnt el posue Prgnay an sti ou n patint wth ovuloy PO an lnc on msl eulay s bs r ore o ptiv pla.
KEY POINT
KEY POINT
• Cntino guoe niring y b uul n psons h pospdal ypecem dawn poeo oveg ge.
• e coie or conrapt p s e oml n ddr h rrgar enses n ss n ptns h polsc or yo.
Bibliography
Bibiography
Klono DC, Buckingham B Crstansen JS. et al Cotinos gucos oniorin: An Endocn Socety Cliical Practce Gidlin Cn Endocrnol Mtab 20; Oc96(10)2968-2979 [MID 297645]
Amsra ESHR/ASRM Sposord 3d PCOS Consesus Worso Grou Consss o wo·s ea asects of olycysc ovary syn dome PCOS m Repro 22 a;22 PMD 227920
f
Item 54
Answer:
A
Educatonal Objective: Treat regular menses and hisutsm in a patent wth polycystc ovay syndrome.
o ppoe eame s coid ral conaceptve ps Hsusm s ese n poximatel 7% o woen wt pyysti ovary syd (COS) T comie o rap pill s ptim ratmnt to adress bh ths pen' ons of estrual irgarit nd sism. T trgn mnnt na hpaic odio x ' ng ee estoseoe eve. o women in om isism is a ajor oncn rtm us o ecn anogn odcio ecesig th ati o cclag t osee nd lmg androg bioatvty to a . Cos thic hairs tht e alreay noted o eamnton wll n to b eoved w deplory mtho; owevr
Item 55
Answer:
C
Educational Objectve: Manage a patent with pheochromocytoma
e mt porat n sep in nagmnt s o begn tatmnt wh n apto atagns, sch as poxybnam. Te o proatv lockad is to povie ood essr ontol nd ecs h ri o crdivasua mpicato elad o exive cecolamin ees dung tatve anipuo of uo Mot patnt ar tra 1 o 2 w bre rgry wt phe x wd ti b o bood esse e age d pre s bow 130/80 mm H g std an grat ha 9 m Hg (ystolc stdig. Bcau o phnoxybnzan e e icug oa, na a tn tig an etoga jaulion som cnicians us shorctng spec angons uc posn, doxas teaz. In ent w cycarda �blockers 12
Answers and Critiques
can be added afer -blockade is achieved. Labeao a com bned and �blockng agent also can be used especialy in paiens wih achyarhyhmias A hea ae of 60 to 70/ min seaed and 0 o 80/min standng can be ageted in mos patients. Paiens wh pheochromocytoma who ae nomo ensve aso should be eaed wh -blockes because hey oen become hypeensive during surgical esection Inceasing the dosage of isinopi does no address the need r peopeaive pharmacologic managemen of the paient's pheochomocyoma wth blockade Alhough ndcated tumo ocaization llowing the bochemica dagnosis of pheochromocyoma, a con as-enhanced adenal CT scan shoud not be permed uni afte an adenocepo anagonis has been initiaed. Admniseing iodne conast meda o a paien who has no receved -bockade coud ncie a hypeensve ciss Similaly, he �adenocepto anagonis popranolol should not be given por o -bockade because unopposed -adenocepo stimulaton coud also pecpitae a hype ensive csis. KEY POINT
• n paiens with a confmed diagnosis of pheocho mocyoma -blockade should be insitued bee sugey o educe he isk of cadiovascula complica tions and o conol bood pessue.
hydocosone is adused based on sympoms such as ohosass wegh loss, nausea vomiing and lighhead edness He does not have hese sympoms so hs corisol deciency is adequaely eated nceasing hs hydoco isone o higher han necessary doses inceases he isk o aogenic Cushng syndome and glucocoicoid-induced oseopoosis His esosteone value is normal and he has normal moning eecions ese ae wo sgns ha his hypogonad ism s adequaely eaed Possibl hs eecile dysfuncion is a resul o igue om hypothyoidism o s funciona insead o physiologc ee s no eason o sop somaropin He has no evi dence of resdua tumor. Gowh homone (GH eplacement can mpove lean mass disrbuion and quaiy of i in a paien with ue GH deciency so t is easonable o con tnue Disconinuing G will lkey wosen his igue. KEY PONT
• Paiens wh seconday hypohyoidsm fom piui ay dysunction have low o low-nomal hyod simulaing homone values so levohoxine dose should be adused based on fee hyoxne (T ) level
Bibiography Sheide H Aett , Keshan-Aderhr et al outis. ae. 207 A 28369957467 MD 74675!7
Bibliography Lenders JW, Duh QY Eisenhofer G et al Pheohromocyoma ad paga glio: a endoe soety lal ate guidele. Cli dorol Metab 2014 un;99(6):95-2 [MI: 289335]
Item 56
Answer:
C
Eucaional Objecive: Manage hormone repacement therapy in a patien with panhypopuitarism.
he patients hypohyroidsm s inadequately eaed causing symptoms of ge and weigh gain and a low ee hy oxne () evel. heree hs levohyoxine dose shoud be inceased Paens wh secondary hypohyrodsm from piuitary dysfuncion have low o low-normal hyodsimu aing homone (TSH values whch canno be used o assess he adequacy o hyoid homone eplacemen Because of his he evohyroxine dose is adjused based on e T leves instead oTSH values His ee T is low, suggesing inadequae teamen as the likely cause of his sympoms. he paiens desmopessin dosing is adequae o ea hi dt npd p w d wihout evidence of xcessive unaion, and is seum sodum eve is nomal n addiion, nceasing he dos would isk poenially causng waer eenion and hypo naemia He is on a physiologc dose of hydrocosone Hydro coisone dose is no adusted based on laboaoy es resuls because his endogenous adenococoopic homone (ACH and cotsol levels wll emain low on adequate thapy and ae heree not used o aler herapy Insead 4
4
122
Item 57
Answe:
A
Eucaiona Objecve Dagnose type 2 abetes meus
A sing plasma gucose measuemen is he most appo priae diagnosc est r his paien. Diabees meius can be diagnosed wih an abnomal esul of one sceen ing test permed on two separae occasions Alhough the hemogobin A is nomal n hs paien he sing plasma glucose is abnomally elevaed wihin he diag nostic ange diabetes mellius When discrepan resuls occu among dieen screening sts diabees the Ameican Dabees Associaon ecommends epeating he abnomal sceenng test. If he epeat sting pasma glu cose measuemen s abnorma, the diagnosis of diabees is conrmed Sceenng ype 2 diabees should begn in all asympomac patiens a age 45 yeas n adul paents wih a BM! geate than or equal to 5, sceening should occu at any age if one o moe addiiona sk cos di i pn. Use o he hemogobin A as an inial sceening es in his pain is appropiate as hee s no evidence anemia o kdney o ive diseas tha coud decrease he reliabiliy of the es he value was norma and does not warant a epeat measuemen as he nex diagnosic tes o perm in his scenaio A hou 7g oal glucose oleance test can be used as a sceening tool diagnosng diabees Snce hs test was no initially used sceening in his paien t s mos
1
c
Answes and Critiques
appropriate to repeat the abnormal screenng test (stng plasma glucose) that was already used r comparson. A random blood gucose measurement would be usel n ths patent f he presented wth classc perglycemc symptoms n the settng o a blood glucose level of 200 mg/ dL (1 mmo) or above, as that woud be dagnostic of dabetes. hs patent is not symptomatc
KEY POINT
• Klnefelter syndrome is a common cause of hypergo nadotropc hypogonadism and aoosperma Bibliogaphy
KEY POINT
• Wen dscrepant results occur among d erent screenng tests r dabetes melltus, the Amercan Dabetes Assocaton recommends repeatng the abnormal screening test
Krausz C, Chaes C. Gic sig ad cousllig r male el Crr Opi Edocol iaees Oes 20 Ju2{3):2450. [MI 3933
Item 59
Answer:
D
Edcational Obective Intepet thyod nction test esuts n an eldely patent.
Bibiogaphy American Dabts Assocao. (2) Classicaion ad diagosis of diaees I: Stadards o Medical Care n iabetes-05 iaees Care 015;38 Supp S6 [PMD 553774]
Item 58
nadsm wth norma prolactn evels herere, measurement o serum prolactin s not the most useful test r ths patent
Answer:
A
Edcational Objectve: Dagnose Kinefelte syndome. e most approprate diagnostc test to perrm next s a karyoype hs patent has evdence o hypergonadotropc hypogonadsm based on elevated gonadotropn levels and low testosterone leve Klineelter syndrome is a common cause of hypergonadotropc hypogonadism and azoosper ma, resultng n nerty A 47X kayotype i s dagnostc of Klneelter syndrome Mosaic variants of this conditon exst but typically present wth ogoasthenosperma, testc ular lure o r hypogonadsm Concomtant symptoms often nclude sexua dysfuncton and generaled tgue Tall stat ure s a common ndng. Patents wth Klneelter syndro me may il to acheve puberty or may present after sexual maturaton wth azoosperma Fertilty may be achieved fom ejaculated sperm, if present or exracted testcuar sperm; however, advanced reproductve technques such as n vtro fertlzaton and ntracytoplasmc sperm necton are necessary to acheve pregnanc Some couples may opt to nclude genetc testng by prempantaton genet c dagnoss and embryo bopsy to avoid transmsson of the dsorder to subsequent generations Typcall, gonadotropn levels are high in patents wth Klnefeter syndrome representng testcular hyponction After plans r concepton are com pleted supplementaton wth exogenous androgens may be consdered to prevent osteoporosis Conception wth donor sperm s an alternatve ertlity treatment opton MRI of the pitutary woud be needed only to rule out a ptuitay mass n the seng o hypogonadotropc hypogo nadm Beaue h atent' onadotropn eve are hh a ptutary mass is unlel Scrotal ultrasound woud ident small testicles in a patent wth suspected Knefelter syndrome, but it would not dent the cause of ths patients eevated gonadotropi evels Seum prolactn level would lely be normal as Kinefelter syndrome s characterzed by prmary hypogo-
Clncal llow-up wth repeat measurement of thyrod-stm ulatng hormone (TSH) and ee troxne (T 4 ) s the most appropriate management r ths patent In persons over 80 years of age, the serum TSH level may be mldly eevated above the typical reference range r younger adults e upper mt of the norma range n ths elderly population wthout thyrod dysncton may be as high as 8.0 µUm (80 m) Since ths patent's TSH level is 64 Um (64 mUL), hs cnical symptoms are nonspecc and hs phys cal examinaton s normal additional evauaton or treatment s not ndcated at ths tme However his clinca symptoms shoud be montored and his seum TSH and ee T 4 leves shoud be measured repeatedy several tmes over a perod of months to ensure that the TSH value s not part of a trend to the development o over thyoid dysnction Because ths patents serum ee T 4 evel is normal and a diagnosis of hypotrodsm has not been establshed he does not requre evothyroxne therap Measurement o the seum tota trodothyronne (T) leve s not tycally helpfu in dagnosng hypothyrodsm because tota 3 evels may reman wthn the normal range well into the evouton o hypothyrodsm However total T 3 leves are use in evauatng patients wth possble hehy roidsm because the value may be elevated out o proporo n to the T 4 level, and lure to recognze an elevated T 3 value may underestmate the degree of ehyroidsm present Total T measures both the bound and unbound thyrod hormone actons whereas the ee T 4 reects the unbound poon o hormone, and may more accurately relect aval able hormone evels in patents who may have an abnormal ity n proten metabosm (such as liver or kdney dsease). However measurement of total T 4 n addton to ee T 4 woud not provde addtonal dagnostic nrmaton in this patent KEY POIN
n paen over year o ae, te erum yrod stmulatng hormone level may be mldly elevated above the typcal reerence range Bibliogaphy Tabaaaie V, Suks M agg yroid Cu Oin dociol Das Oes 01 Oct0(5559 MD 39777
123
Answers and Critiques
Item 60
Answer:
B
Educational Objective: Evaluate an incidentay noted adrenal mass.
e most appopriae diagnosic es to perm ne is the low-dose dexamehasone suppession tes o sceen the auonomous secreon of coso. e inceasing use of imag ing stdies various medca indications has eveaed oth ewise unecognized adenal masses in ess han 1 % of the populaion younge than 30 yeas and up o 7% of hose olde han 70 years. Ten to 5% of adenal ncidenalomas ae func iona, alhough mos have no ove cinca maniestaions. heee esing is usually necessary o ideni functional umos seceing caechoamines cortisol o aldoseone. Of he nctiona adenomas, mos secree ecessive amounts of coisol In subclinical Cushing syndome (S) cassic signs o symptoms of cosol ecess ae no obseved; however complicaions of long-sanding hpecoisolism may esul. e paien has wo dsoders ha can be seen in assocation wh subclinical CS: type 2 dabetes melus and oseopoosis Obesity and hertension ae also common e lowdose oveigh deamethasone suppresson est is ecommended as he ina sceening tes his condition due o its high sensitviy Screenng pheochomocyoma, such as by measung 24hou urine acionaed meanephnes and caechoamnes is also ndcaed in all paiens wth an nci denaly noted adrena mass. Adenal vein sampling (AVS) is not needed AVS is most ofen permed to evaluae a biaeal vesus unilaeral adrenal cause of pimary hypealdosteonism. Measuement of plasma enn activy and adoseone concenraion is not ndcaed n patens withou hypetension No he estng s also inappopiate Athough he magng chaaceisics of he mass ae n keeping wih a benign adrenal adenoma furhe diagnostic evauaton s needed. is includes esting auonomous homona secreton and subsequen adiographic suvelance (rst a 36 monhs and hen annualy 12 yeas) KEY POINT
• Ten o 1% of adenal cidentalomas ae nctonal bio chemical esing is needed o deni ncional umos seceng caechoames coiso o aldosteone. Biblogaphy Zeiger MA. Thompson GB. Duh QY, et a The Amercn Association of Cincal Endocrinologists and Amean Assoation o Endocrine S am mas. nocr Pract 2009 J-Aug; upl :1 [MID: 19632967}
Item 61
Answe
KEY PONT
• The pimay heapy acomegay is ansspheno dal sugey o emove he causaive gowh homone seceing piuiay adenoma. Bh elme Acomegy pogenesis n treament Cn Inves 9 No9389- MD 1988466]
E
Educational Objective: Treat acromegay with transsphenoidal pituitary surgery
ranssphenoda resection of he puitary adenoma s he iniia eamen of choce in paens wh acomegal It is also the only eatmen hat s poenially curative. Because 124
this paient's umo s nvading he le cavenous sinus and compessing he opic chasm complee resecion wil ikely no be possble howeve surgey can eecively debulk he umor and preseve vision n addon o signicany deceasing growh homone (H) secreion as measued by insun-like gowth co 1 (IF-1) levels n paiens in whom compee esection s no possibe such as hs paen add iona heapy may be euied such as seeoacc radiaion heapy o medical theapy o inhibit H secreon or block its eec on he ssues. Howeve, sugica esecion emains an essenial s sep in he eatmen of acomegal. A small numbe of H-secetng ptuay adenomas cosecee prolacin. Although dopamine agonis heapy with agens such as bromociptine would trea he assoc ated poacin elevaion i is mnimaly eecive n acomeg aly and woud no adeaely ea H seceon o address he mass eec of a H-seceing adenoma. A H ecepo blocker pegvisoman s availabe. Peg visoman woks in he peipheal issues as an antagons o H bu does no decrease s poducion by he umo s patient needs inervenion to ea mass eec a hs ime because the umo s damaging he opic chiasm and he patients vsion and his reamen would no be expected o decease the umor sie Somaostain analogues such as oceoid and lan reoide, nhibi H secreion and ae helpfu in eaing some paiens wih acomega ey are used pimaly n paents wih unesectable umos whou signican mass eec or hose with a conandicaton o suger ey may also be used in paiens wh coninued H secetion owing ncompee anssphenoida esecion However, hey woud no be an appopiae eatment in his paient wh a age invasive vsionheaening puitay tumo. Radiaion theapy may be added o sugcal o medica heapy o help incease he chance r emsson or cue. Radaion o he piuiary carres a high rsk of causing puiary isuciency and damage o suounding tssues (pariculary he opic nerves) theree s no usualy an iniial treamen r acomegaly in most paients. In hose in whom it is used, sereoacic sugey (gamma knfe) is he pefeed appoach o minimze potenial complcaons.
Item 62
Answer
C
Educational Objective: reat high-risk thyroid cancer postoperativey
Radoacive iodine (RAI) heapy is the mos appopriae pos opeaive eatment in his paen who s a high isk of
Answers and Critques
cancer ecuence based on hs age, the size of he pmay umor the pesence of vascula invasion and extrathyoda extension, and the numbe o invoved lymph nodes He theere may benet om adjuvant AJ theap, which may decease the likelihood of recurent disease n patients with nodal metastases. hs is given in conunction wih levohy oxine suppession theap, whch s indicaed in a paents who have had a total thyodectom Because of hs high-is disease it would be appopae to lower he thyoidstimu ating hormone evel to less than 01 µ/mL (0 m/) in he absence of containdications such as peexsting cadovas cula disease o age geate han 65 years Tadtiona chemotheapeutic agents such as doxou bicin, ae geneally ineecve in the management of de entiated thyoid cance and would not be indcated this patient In patients wih anaplastic cacinoma of the thyoid howeve, some studes have demonstrated a possble benet with concomtant use of pacliaxel based chemotheapy and extenalbeam adotherapy his paien has classic pap illay tod cance histoo and would no benet om such teamen Externabeam adioherapy is arely used i patints with dieentiated thyoid cance An exception would be the management of patients wih inopeabe disease tha theaens to cause oca extension into vital strucu es in he neck such as the tachea esophagus o maor bood vesses Because of the exent of disease und at surgey and this paent's high sk of recurrence, poviding no addi tional theapy would not be an appopate next step n management KEY POINT
• A patient who has undegone total thyodectomy thyoid cance and is at hgh isk disease ecurence should eceive aduvant adioactive iodne theapy
insu is he ecommended eamen Unike autoimmune ype diabetes chonic panceatitis aso destoys the pance atic alpha cels causng a glucagon deciency that inceases the isk of sponaneous hpoglycemia Glucagon acs on the lve to incease glucose poducton though gycogenolysis and guconeogenesis. he ecovery om hypoglycemia is also impaied wth alpha cell desucion Ealy ecognition of hpoglycemic symptoms and staegc hypoglycemic teat men plans should be emphasied wih patiens wih pance opvic dabetes xenaide, a glucagonlke potein1 (GP) mimetic, suppesses glucagon and pomotes insuin secetion he pancreatic beta cell and alpha cel destuction associated wih chonc panceatis pecudes ths teatment option Postmareting epots o panceatis ae also cause r con cen the use of this cass o medicaton n patients wih a histoy o f panceatis e sunyluea glpiide increases insuin secetion he eec would likely be minima to nonexistent in this patient wih hypeglycemia esulng om subsantia beta cel desrucion om chonic panceattis Metmn deceases hepac glucose output by nhibi ing gluconeogenesis and inceses insulinmediated glucose utilation in peiphea tissues Metmin s a stline agent r initia teatment o ype 2 diabetes; howeve, this patient has an insuin decency om panceatic beta cell desuction and should be teated as a patient wih type 1 dabetes KEY POIN
• Hypegycemia caused by chronic panceattis is an acquired m of type dabetes melltus and should be teated with insulin Bbogaphy Meene K Bale Croc paeatts Laet 997 ov 83509088) 3985 [MI: 936465
Bibliogaphy Jokaas J, Sarls N Ltofsky D, et al Outcomes o patients wt dfeet ate hyo cacinoma llowing ital era. Tyro 2006 ec;6(12): 1229-42 [PMID: 99433]
Item 63
Answer:
C
Educatonal Objectve: Manage acqured type 1 diabetes mellitus.
is paient has an acquied m of te diabetes meli s caused by chonc pancreatitis (panceoprivic diabetes) which necessitaes the use of insulin teatmen of the hypegycemia Chronc panceatitis resuls in pemanen duct f th c d th th d cine and exocine functions of the panceas e pance atic exocine abnomalities aise om loss of the panceaic enzymes equied r dgestion and absorption o od e panceatc endoce abnomaities can pesen in a simila manne as ype 1 diabetes wth peglycema om insuin deciency seconday to desucion of beta cels eee
em 64
Answe:
A
Educationa Obective Teat nfety reated to poycystic ovay syndome
he most appopiae teatment is a selecive estrogen recep to modulato (SERM) such as clomiphene citae SERMs ae the esablished stine teatment ovulaion nducion n anovulatoy paients with inferility om polycystic ovay syndrome (PCOS). ypicall, theapy s stared aer menses and s gven orally days Common sde eects include vasomoto sympoms and mood changes scalatng doses o clomiphene are typcally pescribed f a patient does not ult w d Mo cl dnc sut th eectveness and possbe superioity of aromatase inhibto herapy (such as with letozoe) in women with PCOS ovulation induction However, ths theapy is no curenly FDA appoved this indication A smal subset of patients with PCOS may eque n vito etilzation but hs theapy is typicaly expoed ony 125
Answers and Critiques
Bibliography
Item 68
Ameran Daetes Assoiation. (9) Miovacla opiat and f ae In: Sandads f Media Cae Daee-2015 Dabee Cae 21 Jan38 Sul S5866 [PM 2557710]
Educationa Objectve Dagnose Asherman syndrome with transvagnal ultrasound
Item 67
Answer:
D
Educational Objective: Evaluate hypogycemia in a patient without diabetes melitus.
1 pn hud und ur \N ygm etng t t m ymtom hyym He d ymmi hygym nd ting (>5 hu) g h reod i u dmn in. Sin n uny yym or ym mtc ng n y in n tm e h maoic cnar h ndud h yym o !· dntv dino Gue nd yymc td . ncudng mumn o nun de. nun nd �ydyutye . ud ond h bgnnn o e and hn rd ery 6 hu un d uco e 0 mg d (33 mm/) me hy ud rd r o 2 hu un ymtm hygm ( m dL 5 mm/]) ccu (2) ymm ygym ( mgd [30 mmo/L) u h rou dumened We ad. or (3) e 72u nud W rd n o hr mnen: nuye n nurrnt hyogyma nd un mm t rn o ypgym. yymic ud a n dequy nma n h pn n nn ymom yogyma; there tin no ud n pre Mdm n n nn m nnn mur n. nd yd nndd m gu he m ren need gu whn ymm hypym ur hn u ar m numon (nd yy m) He hi n' ymm hyogym ud 7 u r m: h u tin r nd hygym h 8 md m oud n re O gu onc n y ud eu nd yym He h no dmnaed n J h ur nd ud n n udy un n yym KEY POINT
• Syptoatc stng ypogl yceia s best evalaed wi gcose and ypogyceic stdes preceding and dring a or st Bbliography Cryer E Axelod L, Gssan AB et al valain ad anageent f ad hyolye dsdrs an doe Sey Ca aie Gdeie J ndno Mea 2009 Ma94)09 - MID 90
Answe
D
he ost appropriate diagnostic test to perorm next is a rns vagin lrond This patient has likey developed Aser man syndrome (AS) Becase the orona evalaton n this patnt upr an intac hypohalaicpittayovaian ais ttra abnoalit uc AS hold be sspected AS an uncomon complcaton of daaton and curetage ntuterine devce paceent or srgica procedres sc as hyterocopc myomectomy t is cased by lack of basa endometrum polirton and rmaion of adesons (synechae) Dgnis should be consdered n any oman wh amenor ra nd pvos xposure to terine ntentaton The ypica presentation is ih secondar amenorrea, a tes aocatd wit cylic pelvc pain created by dstenion of he erne cavit were pockes of nctional endometi pesist bt ex of mensta lo s bocked or sloed by adesion foion. Atogh soe patients it AS ay be cmpletey amenorrhec oes ma y demonste hypomenorrea and report scant menses compared wth the volme of their ensr w bere he pocedure AS most comonly occurs n n nlmmato ettng sc as endometris or septc aborton. AS may alo occur as a result of an overly aggessive crettag In paient wit AS trnsvagnal ltsond wll o thin ndmetria strip and may reveal smal pocket s of id wer menstrual ow has een trpped by neighboring adhesons. A funiona terine eaination, sch as ysteosapngogrm or aine onoysteogra, cons the diagno ratnt con o hytroscopc resecton of esons ven tis patents normal gonadotropn eves, a pititr cause r her secondry amenorrhea is nkely there re imagng of he piiay no warraned at thi te Preature ovaran nsuciency is not te ost lkely dagnsis given this ptins normal etdiol and gonadoropin level terre, a perpe karyotype wold be expected o be noma and shod not be perred. Rests f progestin wthdrwal test are used to delin ee between an esrogendecient sate (no bleedng) and an ogensucen tte (ithdraa beedng). I the patent is prodcing estogen se wi have wdrwal beedng witn ee competing a coure of pogesterone If no wih drawal bleeding cr ae e progesterone callenge ten the patent has ether a owestrogen state and hypotalaic amenorrea s the dagnoss or tre s terine otow bock age. Ths ptien story of a prevos tene pocedre pror to te onset of amenorrea and the possiblt of denuded endomerm where synecae are presen will make a negatve test (no wthdra beeding) nntepretable. P
e dagnosis of Asheran syndroe sold be consdered in any woan with aenorea and prevos exposre to terne instrentation te classc presentation s it secondary aenorrea and soetes cyclic pelvic pain 127
Answers and Critiques B
Bibliography
Item 70
C D P M : ' 3 271118 [PMI: 243732]
Educationa Obective: Treat Gaves ophthalmopathy
Item 69
Answer:
C
Educational Objective: Identify postprandia hypergycemia as a cause of elevated hemogobin A1c leves.
Ths patient should measure her postprandial blood glucose level Given the patents young age and lack of oher major comorbidities her hemogobin A goal is less than .% to 0% ostprandial hyperglycemia oen remains undetected but still contrbutes to elevated hemoglobin A values The ect is more profound when the hemoglobin A is close to .0Y Adequae meal-ime coveage wih insulin can be determined by measurng postprandia bood glucose evels lf her - to hour postprandial blood glucose vaues are ele vated above 0 mg/dL 00 mmo), her meal-time insulin should be increased or the composition of her meals should be altered to decrease her blood glucose hanging her det f it is causing postprandial hyperglycema could eventualy ead to lower insulin requiements hecking he postprandial bood glucose values st will help identi whee the hyperglycemic issue arises that keeps her hemogobn A above goa ncreasing he glargine dose will no adequately act postpranda hyperglycemia and may lead to overnight or sting hypoglycema Oveght glucose abnormalities can be identied with the measurement of a blood glucose level. arge uctuations in sting blood glucose values or consisten sting hyperglycemia can be clues to overnight hypogly cemia with subsequen rebound hyperglycemia (Somoi ect) or hyperglycemia as a result of rising catecholamines dawn phenomenon Te paten epots sabe sting and preprandial glucose values throughout the day. le most likely timing r glucose abnormalities that would ac her hemoglobin A vaue is in the postprandia sate Sitagliptin is a dipeptidy peptidase- (-) nhb itor tha slows gastric emptying and suppresses glucagon secretion Although it has a modest eect on hemoglobin A lowering metrmin remains rst-line therapy r type diabetes and should be continued as part of her regimen. 1
1
1e
1e
1
1
KEY POINT
• ontoring postpandial blood glucose levels can be useful to assess prandal insulin coverage in patients who have ype diabetes melitus with a-goa pre pandal readings but with hemogobin A values not at goal. Bibiography
D 7 I: M C 15 C 2 J;8 1: 8 PMID: 2537 128
Answer:
ethmazole is most appoprate r this paten with Graves ophthamopathy (GO) GO may be manfested by lateral gaze palsy sceral injecton, periorbital edema and pressure sen sation behind the eyes. Additional manifestations include proposis lid lag and, if severe decreased visual acuty. Excess deposition of glycosaminoglycans in the retro-orbtal space resuls in increased pressure the ensuing compression of the muscles and cania nerves causes the ocular palsy. ost patents wth GO have mild nonprogressive symptoms hat do not requre specic treatment The decision to treat depends upon the severty and activty of the dsease. Fr patients who need reatment, initial therapy shoud arget controlling the hypethyroidsm. ethimazole will apidly lower circuaing thyoid hormone levels, may reduce serum hyid autoantibody titers, and may assist in contolling GO symptoms Additional therapy to control sympoms ncludes use of ocular lubricants and taping of the eyelids at night if the lids are unable to completely cover the eye). Because cigarete smoking increases the activity of GO and inpairs the response to therapy, smokng cessation is of paramount mpance. External-beam radiotherapy is reserved r treatment of severe GO but typically is employed if symptoms persis or worsen in spie of eu to the euthyroid state ecause radioactive iodine RA) treatment has been assoced with (at least transient worsening of GO due to an inia increase in circulating antibody levels, its use is not recommended in patients with modeate to severe GO When RA is used, pretreatmen with a glucocoricoid to mtigate the rise n antibody level is recommended pror to RA! therapy otal hyroidectomy is typically eommended r long term contro of Gaves disease n patients wih active GO when medica heapy is to induce a emission However retuing the patient to a sate of euthyroidism is advisable bere surgery Surgical decompression is also an opton to control acive GO, paticularly if there s compression of the optic neve. KEY PONT
• Int treatment of Graves ophhalmopathy is nor malization of thyoid unction Bbography
P P K M 4 669 M 9665 tem 71
Answe:
B
Educationa Objective: Diagnose primary hyperadosteronism as a cause of secondary hypeension.
he most appopate diagnostic tes to perfom net is to mea sure the plasma aldosterone-plasma renin activty ratio This paient has resistant hypertension dened as blood pessure
Answers and Critiques
nclude diagnostc lapaoscopy, but this is not ypically per rmed as rsine evaluation gven he need general aneshesia, inubaton and ecovery. Repair of the lopan ubes may be possible wih microsurgical techniques; however reoccluson is possible and the risk of subsequent ectopic pregnancy is high. Many women elec o proceed wth in vtro fetilization n lieu of tubal sugey. Ovarian eserve assessment and semen analysis ae essentia when evaluating a couple wih infeti Ovaan eseve assessment can be accomplshed with eary follcuar phase testing of liclestimuating hormone (FSH) o anmleian hormone (AM. ransvaginal ultrasound in he ealy llcular phase allows fo counting of antra lices n each ovary which if presen at greaer than eight bilateally support normal ovaian reseve. However gven this paient's history of pelvic inammatory disease and he husbands hstory of thering a chld in a revious maage HSG s the diagnostc est that s most ikely to evea an abnomaliy. Semen analysis can be permed after a shot window of abstinence on an ejaculated sperm specmen. However, it is unlikely to be helpful in this paients husband. Karyotypng s usually not indicaed as par of the inia evauaion of unexpained female infetiiy because of the low ncidence of discovered abnomaltes. Specialized laboratories wih androo services evauate sperm concenation sperm motility, and sperm mr phoo Ovarian eseve may be evauated by serm testing (day 3 licestimulating hormone leve, AMH level) o by transvaginal ultrasound assessment of anral ice coun. y
and pheochromocytoma. aure to ideni and reat a pheo chromocyoma pio to surgey can resu in an inraopeative hypertensive css and potentiall death. Whle i is mportant to assess the risk of metastatic disease n ths highisk paten, 8uorodeoxyglucose posron emission tomography scanning is not the deal imaging modaity in patients with MTC as there is a high lsenegatve rae. T of he lungs and liver is a more eective eans of identication of disan metastases While evauaion for hyperarahyrodism by measuring the seum paahyrod hormone leve is indcated in this patent with MEN2A t is no the most approprate nex sep n management. Testing r hyperparathyroidism is recommended prio o surge because he parathyoid diseas can be managed simulaneousy wth he hyroid cancer but would no be an appopiate step bere evauang a patient wih MEN2A fo he presence of pheochromocytoma Total thyoidectomy and lateral neck dissecton should no be permed unti it is conrmed that this patient does no have a coexsting endocrine neopasm owing to th e high ntraoperave isk associated with untreated pheochromocytoma. f identied pheochromocomas should be surgicaly emoved prior o hyroidecomy Genetic counselng is a very impotant component of the treatment pan al patens with newy diagnosed MEN2A as stdegree elaives are at high sk r aso hav ing he RET muation Wih a neary 00% penetrance r development of MTC in carres of RET mutations, referral o a team wh experience in the managemen of these disoders s crtical fo timey diagnosis and treatment.
KEY POINT
KEY PONT
• Primar infeli due to a ubal abnormai is com mon particularly in women wih a histoy of pevic inflammator disease and is best evaluaed with a hysteosalpingogram.
All patients with multiple endocrine neoplasia e 2A should undergo testing o exclude pheochromocy oma prior to hyoidectomy; an elevaed leve of pasma acionated meanephrines should pompt treament r pheochromocyoma bere addressing the thyroid malignancy
Bibliography Maheux-Lacroix S. Bouin A. Moor L. t l Hysoslpigsorphy for dagnoig ba ccluio uril wmn: sysmt viw wih mea-ayss m Rr 2014 My9(5)953 6 [PMID: 2787]
Bibliography
Item 74
Item 75
Answer:
B
Edcational Objective: Evalate newy diagnosed meduary thyroid cance.
e nex most appopate sep in he anageent of his patient with medulay thyroid cancer (MC and multiple endocne neopasia pe 2A (MEN2A is o evaluate r the presence of a pheochomocyoma by measuremen of actionated plasma metanephrines. Al paients with a cytologc diag nosis of MTC shoud undergo tesing of the mor for genetic abnormaites as the ntial step in hei evaluation as 25% of paients with MTC will have he nherited rm Identcaion of a mutation in ths paient means hat the he has MEN2A an inheited syndroe associaed wh hyperparahyrodsm r
130
Ami Thyroi ssciain Guils ask Foc,0 yo [MD: 8007
Answer
C
Educationa Objective Treat severe ypercacemia
i n see ainnra nn [ J d s ns nd dn nur iai i n ies ey h r s (>8 L 4 ml ]) aso i!h e in n !ha pecuds !r a eae b1s i abe dy sm cu ad de 1rfl mnaen of ue sus d erls Bth hdalss and ritna dss r ptns hh hdasi r wers liu
C
Answers and Citques
assessment of LH suge and antcipated ovulation in patents wh PCOS woud be toug transvagnal identcaon o ovarian ollculogenesis and conmaory serum assessmen o reproductve hormones. ate-onset (noncassic) congental adenal ypeplasia, altoug a common cause o hirsutsm and oligo-ovuaton s typically assocaed w normal or ow H levels owng o e negatve eedback o elevated andogens o adenal orign on he anteror putay Functonal ypothalamic amenorhea aects 3% o women between te ages o8 and 40 yeas and s a dagno ss o excluson Ris ctors s condition nclude a ow body wegt and t pecentge apd and substantal weg oss eating dsordes excessve exercse severe emoiona stress sevee nutriona deciences and chronic or acue lness FSH and H levels are napproprately low or normal and canno account r a posve urinay H test Hpohyrodism and eevated serum prolacin evels suppess rathe han elevae serum H levels and would not account r ths paten's nceased urnary H measuement KEV POINT
• Women wth polycystc ova syndrome pcally ave elevated restng lutenizng hormone (H levels wic may be mstaen on home urnary H ts ovulaion
Roterdam ESHR /ASRM-Spnsr PCOS Conssus Wrkshp Goup. Revised 2 003 cssus on dgos rira an log tr heat rss r t poycystic oa snde Fer Ster 4 Ja:81(9 5. [ID 7538]
Answer:
C
Edcational Objective: Teat a high-isk patient with osteopoosis.
Ater counselng bout smong cessaon ths paten should contnue er current alendronate therapy She as documented osteopoross and is a g rsk r subsequen actures due o mutple is ctors ncludng curent smong and a prevous racure Her bone mneral densty BMD) as been well mananed on an oral bisphosponate r te las severa yeas e bes wa o evaluae a dual-en er x-ay absorptiometry DEX) scan rom measuremen o measurement s to compare the bone mnera densty readings om year to year, not the T score cange in BMD hat s less han about % o e percentage noed by he A macne mnuue o ondeed ttt cal signcant chnge hs egmen soud be consdered successu eap snce te goal of bsposphonates is not to bud bone mass bu to stabilze bone loss Snce ths patien as had sabe BMD we on alendonate tee s no ndi caton to convert to a moe nvasve expensve option at is tme It wl be mporant, howe ver o coninue to llow he r atpical acures o e long bone due to er prolonged bisposponate treatmen leg pan or an atypca racue s noted bsphosponae teap shoud be disconinued. 132
KEV POINT
• n patens at gh rs r osteopoross t s appropr ate to contnue bsphosponate terapy alone ade quate bone stably as be en acheved Bibliography Nata Oseopss otio www yof.g boesource) Cincan's Ge t eeto ad Trtt Oseopoross shigt C Naa Osteoprss uo
Bibliography
Item 78
Denosumab s a ecepo actvao o nucear cor KB (RAN) lgand inhibor FDA approved r the treament o osteopooss n postmenopausal women wo are a hig is o acture Snce tis patent as no led bsposphonae therapy shown a signcant decrease n BMD whle on bsphosphonae therap nor s she noleran o the curren erapy there s no reason to cange er therap Terparatide is approprate as rstlne therapy r patiens at high is r acture (T-score < 30) or wo ave experenced pogressive osteoporotc dsease wle on bsphosponae therap is cange would be unnec essar since te paten's BMD has been mantaned r the pas 5 yeas A drug holiday s ndcaed r patents who have been on bisposponate erapy r 3 to years have ad no progresson of the dsease and have mnma risk ctors addtonal fractures. 1s patent has muple rs c tors ractures; erere a drug hoida would not be appopiate
tem 79
Answer
D
Edcational Objective Manage pimary hypeadosteonism
he most appoprate reatment r ts patien is spronolac tone He as pmay yperaldoseronsm P) due o a bilat el adrena souce as evidenced b the Jac of lateralzation on adrenal ven samplng (VS Blaeral adenal yperplasa s te most common etolo o accounting approx mately 60% o cases and sponolactone s the teamen o choice Spironolactone is a mneraococod ecepor MR) antagonst tha can mpove bood pressure, normalze serum potassum concentaton, and reduce excess cardovascuar s related o hperadoseonsm Eplerenone s an altea tive MR anagonst that s ess ley to cause necomasa n men because o geater MR selectivity however, use o eplerenone this ndcation s o label Antagonss o te adoseone-senstve sodum channel (amloride) can be used eonde tap Bateral adenalectom s not appoprae r he rou tne management o PA, as ts would rs primay adrenal ilure tus necesstatng lelong glucocotcod and mn ealocorcod therap Dexametasone a longactng synteic glucocortcod has a roe n reang on a smal percenage o patients wo have glcocorcod-remeda ypetension a vey are auto somal domnant condton resulng om ectopc expres son of adosterone snthase n he cotso-poducng zona
Answers and Critiques
sciculata. Administaton of dexamethasone will suppress pituitary adrenocorticotropc hormone (ACH) secretion in these patients and therere minealocorticoid production. However, hypeadosteronism in most patients is ndepen dent of ACH secetion and suppression with exogenous glucocorticoid s not an eective therp Left adrenalectomy should not be errmed because the patient has a bilateral cause of PA e eft adrenal adenoma detected by C scan is an incidenta nding and is likely not the cause o f this patient's hyperaldosteronism Because nonsecreting adrenal adenomas are common, AVS is needed n most patients with hyperaldosteronism to determine the source of adosterone secretion when imag ing studies show an adrenal adenoma to assess its contibution to excess mineraocoricod producton. AVS should be done at a hghvolume refera cente due t o a hig risk of complications when signicant procedurl experience is ackng KEY POINT
• or patients with prima hyperaldosteonism due to bilatera adrenal hyperplasia medical therapy with a mineralocorticod antagonist such as spironoactone is the reatment of choice because of its proven efficacy to lower blood pressure, normalize serum poassium concentraton, and reduce cardiovascuar risk. Bibliography JW RM : E M 2008 ;9393266 81 [MD: 185588
Item 80
Answer:
B
Edcational Objectve: Manage hyperprolactnema cased by hypothyroidism. Ie most appropriate treatment for this patient is o begin evothyxine. She has primay hypothyroidsm with an elevated thyoidstimulating hormone eve and a low fee thyroxine 4 level. Her symptoms are consistent wth hypothyroidism. Hypothyroidism is a cause of hyperprolactinemia en patients present with hyperprolactinemia and hypothyrodism the hypothyroidism should be teated and then the patient shoud be reevauated to ensure that the hyperprolactinema resoves The patients piiary gland s nomal There is no mor. he hypothyoidism should be treaed st and then the patients prolactn level shoud be eested. ere s no indication r cabergoine a dopamine agonist a hs poin n w hyperpactinemia caused by a proactinoma. his patients hyperprolactinemia is expained by hypothyoidsm Sertaine does not cause hyperprolactinemia or hypothyroidism. Antipsychotic agents are a common cause of hypeplactinemia but selectve seotonn reuptake inhibitors sch as sertraline are not
ere s no indicaton ptuitay I at ths time because her hyperprolactinemia is expained by hypothyrodsm I is necessar y to make sure that her hyperprolactinema nomalizes afte treatment with levothyroxine KEY POINT
• In patients with hyperpolactinema and hypothy roidism the hypothyoidism should be treated st, then the patient should be reevaluated to ensure that the hypepolactinea resolves Bibography M M 1 2 27388 MD 1296991]
Item 81
Answer:
B
Edcational Objective: Diagnose cystic fbrosis as a case of congenita bateral absence of the vas deferens and azoosperma Congenital blatera absence of the vas deferens is a common cause of obstructive azoospermia and is reuently associated with cystic bosis CF). It may also resent with uniateral absence of the vas defeens any patients ae unaware tha hey have CF because hey may have a md rm that causes ony nonspecic sympoms such as chronic sinusitis Paner esting r CFcarer satus shoud be encouraged to assess he likelihood of tansmission to a subsequent generation. Sperm pduction is often normal in these patients however, the absence of the vas deferens mits any obsevable sperm in the ejaculate. Theere testicuar biopsy is necessary to rerieve sperm for use in advanced reproductive techniques (A) such as in vitro fertizaton and intracytopasmic sperm inection. Utiization of donor sperm is an alternative for coupes not interested n A. Andogen abuse is common among eite and pofessional athletes and in young men. Physcal examination ndings may incude excessive muscular bulk, acne neco mastia and decreased testicular voume. ow sperm counts also may be present with exogenous andgen use. Andogen abuse can result in hypogonadism and infertilit which occasionaly are ireversible Is patients normal physica examination normal testicua voume and absence of the vas deferens argue aganst this diagnosis Prmay hypogonadsm is due to testicula iure and s dened as a low testosteone evel with elevated luteinzing hormone and lliclesimulating hormone levels. Primary hypogonadsm can have congenita or acquired causes Te mos common congental cause is Klinefelte 4XXY ex x hr some resuts in marmation o the seminifeous tubues and ycaly of the eydg cels ysica examination is likely to reveal smal m testes and deceased virilizaton. Addtona manifestations include ogospermia and infertilit inefeter syndrome does not result in obstructive azoosermia due to absence o the vas deferens 133
Answers and Critiques
A clinicaly papabe varicocee typcaly aects fertiity by owering spem motility though a oca heat eect A scotal buge may be noed by the cnician, and the patient may note pan that is wose wth he Vasalva maneuver. Azoospermia would not be caused by varicocee aone Y chomosome micodeletions can be associated wih oligospemia o aoospemia and smal testicua voume hs chomosomal abnormalty s not associated with absence of the vas defeens and s theere not a ikey cause of hs patients ndings KEY POINT
• Congenita batera absence of he vas defeens is a common cause of obstuctive azoospermia and is fe quenty associated with cystic fbosis
KEY POINT
Bibliography Stahl PJ, Schlegel N. Geei evio of e zoosperm o severely oligozoospemi m e Cu Opin Obse Gyeo 2012 Ag;24(4):221-8 [MID 2229088
Item 82
Answer:
B
Eucatona Objectve: Manage prmay arenal falure. Initiaton of cotsol repacemen therapy wth a gucoco ticoid (such as hydocortisone) and mineaocoticoid (such as udocotisone) s the most appopae nex step in man agement his patient has symptoms consisent wih adre na nsucency (tigue, unnentiona weight oss, nausea and vomiting); he mily hsoy of autoimmune disordes hyperpgmentaon noted on physica examination and hypekaema on aboatory esing sugges pimay adena iue. Patients with primay adenal iue equenty have inceased pigmentaion ove the exenso suces and bucca mucosa due o the excessive seceon of meanocte-stim ulaing homone, whch shares a common precursor with adenocoricotopic homone (ACTH) Hypekalemia occus due to deciency of adosteone 'e diagnosis of adrena insuciency s made by documenting an inappopriatey ow seum coriso leve. An eay monng seum cotiso leve that is ess than 3 µg/dL (828 nmoL) in the seting of signs and sympoms of coiso deciency is diagnostc of this diso de Teatment should not be wthheld whe awating futher diagnostic testng since adenal insuciency is a potentay fe-threatenng condition hat may esut in hemodynamic instabiit Teament of pma adenal ue reques both glucocoticod and mineraocorticod epacement Hydoco n n nn n m ticoid activty should be gven aong with a mineaocoticoid agent such as ludocotsone. e synthetic ATH (cosyntopin) stimuaion es is extemey sensitive r deecing either pimay or second ay adena nsuciency n patiens with nondiagnosic basal cotiso vaues (4-12 µg/dL [11043312 nmo!L]) stim ulaton testing with synhetic ACTH is indcaed A norma response is a pea serum cortiso geaer than 20 µg/dL (552 nmo). ACTH simuation esting is not needed if the 134
eary moning seum cotiso eve is unequivocay ow, as in this patent Measuremen of the pasma ACTH leve is used to di ferentiate pimary adena ilure fom other causes of ow cortiso n pimar adenal ue, he pasma ACTH eve is ypcay sgnicanty eevated (200 pgmL 44 pmoL) and woud conm the diagnoss Howeve, withhoding the apy while awaiting diagnosc conrmaon woud not be appropiate because of he potentia ife-heatening naue of primary adena iue Ahough pednisone is an acceptabe agent r gu cocoticod epacemen it has amost pue gucocoticoid activy and woud no be an appopiate singe agent reatment of pmay adena iue in which eplacement of both gucococod and mneaocoticoid s required. • Cotiso epacement theapy shoud be initiated immediatey in pesons with coned adena insu cienc which is diagnosed by an eay mornng seum cotiso eve beow 3 gdL (828 nmoL) n he seting of signs and symptoms of cotiso decienc Bbography ey N Niemn L de sufiiey eoo dgss tetme u Opi Edorl Dietes Oes 2010 u732-2 [M: 205886]
Item 83
Aswe:
A
Eucatonal Obectve: Manage the "oneymoon" phase of type abetes meltus. he most appopate management ths patients hypo gycemia is to decease nsuin glargine and nsuin aspat. he gucose toxcity present at the tme of diabetic ketoaci dosis has diminished with an nensive nsuin egimen He emanng functiona pancreatic beta cels have egained the abiity to poduce some insun in the "honeymoon phase which expains the hpogycemia on previousy weltoe aed doses of insun he deceased need insulin wi not be ong erm as pancreatc beta ces continue to be desoyed ove the couse of tpe 1 dabees Continuing insulin, eve n at ow doses is recommended duing the honeymoon phase in ode to peseve beta ce unction as ong as possble by educing the meabolic stess on these cels e ow dose nsuln regmen can consst of a basal and pandial insuin combination o a basal insun regimen She s expe nn mm n n n mia Decreasing the insuin aspat and nsuin glargine doses woud address the pandial and sting hypogycema whie aso sti povding ow-dose insulin to potect the function ing beta ces he w equie close monitong of her bood glucose leves to detemne when nsuln doses shoud be inceased as she nears the end of the honeymoon phase he honeymoon period may pesist severa weeks to months Mea-tme nsuin doses ae geneay educed by 50% when pramintide s iniiated due o he isk of hypogycemia
Answers and Critiques
The addition of pramlntide would likely exacerbate te cur rent issue of ypoglycemia even wit reducton o meal-time insuin. e use o slidingscale insuin wtout basal insuln is discouraged When slidingscale insulin is used witout basa nsulin te likeliood of wide swings om ypegly cemia to ypoglycemia ncreases Witout a basal insuin regimen, se may not consistenty receive daily insuln to decrease te metabolic stress on er unctioning panceatic beta cells. Discontinuation of bot insuln glargine and insuln aspart increases metabolic stress on te panceatic beta cels and accelerates te loss of unctional cells producing insuin. As pancreatic beta cell fnction decnes toward te end of te "oneymoon pase te isk of dabetic ketoacdoss increases witout any exogeno us insuin. KEY POINT
• Continuing insulin even at low doses s recom mended during te oneymoon pase of type 1 dia betes mellitus to reduce metabolic stress on nction ing beta cells and peseve any residual function r as long as possible Bibogaphy DeWit E, Hrsch 1 Oupaet nsu eapy yp lad pe 2 be es meus: scenc revw JAMA 2003 My 7;289()2254-64. [PM 27343]
Item 84
Answer:
commonly demonstrate ogoastenospea (reduced sperm moty) and at times complete aoospermia Tee monts of teatment are yically needed prior to reurn o f improved semen parameters. Proactin is seceted by e piuitary lac totrop ces under tonic nibition by dopamine Dopamine agonist teapy can normalize prolactin levels reverse ypo gonadism and sin umos by at least 50% in almost 9% of patients. Evaluation o te inerle male wit abnormal ndings on semen anaysis sould always include investi gation of te ypotalamicpituitarytesticular HP) axis Disturbances in tis axs may resut n ilure of gonadotropn release om te anteor ptutary and nsucient testosterone production as well as absent or dminsed spermatogenesis. lomipene citrate is eectve only wen te HP axis is ntact wc does not apply r tis patient Altoug te indcation r clomipene citate n te infertie mae population emains controversial some clinicians use it to increase endogenous lliclestimuating ormone and lutenizing ormone output fom te anterior pitutary to support testosterone production by Leydig cells Sildenal may improve erectle dysfnction in tis patient but it will not ncrease endogenous testosterone levels and wll not impove is yperprolactine mic state. estosterone replacement terapy would e elpful to alleviate te sexua l side eects of ti s patients yperpro lactnemic state owever no restoration o spermatogenesis would occur and teere infertilty woud persist. Neit er testosterone replacement nor sildenal terapy will educe te size of te patient's prolactnoma
A
Educational Objecive: Treat hypogonadsm secondary to hyperproactnemia in a mae patien.
e most appropiate treatment s a dopamine agonist suc as caergone Hyperprolactinema as a result of a prolactinoma is a possible cause of erectile dysnction and decreased libido and may be successy treated wit a dopamine agonist. In addtion to te sexual dysncton assocated wit yperpro lactinemia semen parameters are oten abnormal; patients
KEY PONT
• Secondary ypogonadism in a male patient caused by yperprolactinemia as a resut of a prolactinoma is a possible cause of erectile dysnction and sould be treated w it a dopamine agonist suc as cabergoline Bblogaphy Man W Treaten r rocoas and yerproacae a fee apro r J C Invest 20 Mar4(3332 MD 2095523
135
Index
Note: Page numer llowe by fand dnoe ge an les. pcve T qeio a ca Q
A bdomal C scan adoge-poducig adrel tumo, Q52
carbose fo detes melus S O CE hibor detc ephropy 17 cqed ype 1 dees 3 comegy 27 cases o 27 clca feures d dgoss n 27 sspeod surgey Q6 eme of 2728 CTH stmulaion test 22 23 deoma aden 32 ptutay,20 ( also Ptuity tumos} tyod toxc 44 dea l ciss 36 deal ilure ae al adrel hemorrage d Q42 dea igue 38 dre gld dsorders of 290 dre omone excess d 3036 adresfcencyd,3639 dre msses 390 eed nomy nd physoogy 29 29' de sucecy,36 drg cc ilness 3839 pmry dre ure 3638 dren msses 390 magg carcersics of 32 cdetaly oed 390 39 QO Q60 deal metastases 39 deal ve samplg (V) 34 deococal cacnomas (CCs) 32,32t 39. 40 surgc excso of,Q27 dreococoropc homon e (C 9 J9 nd corsol prodcon 29 dececy of 2223 23 gg me drogen defcecy 5758 doserone 29 doseoneprodcg adeocotc denoms 3 ledroae r oseopoross 69 Q78 r Paget dsese of oe 7 loglpn, daetes meus O -deocepto s bockes fo pheocomocytoms 33 -glucosidse ibitos type 2 dibetes. 4 St Ot meoea 555 evaluatio o 55 prmay 54,Q9 secod 555 meca Dbees ssocon on screeg r ype 2 dbees I 2 morde prmy hyperdoseronsm,35 modroneduced hyooxcoss () 6 type 6 ype 2 6 mptyie ds symmerc poyeuophy 18 mylommetcs r dees meius O nolc steod se me 60 , w doge decncy gg mle 5758 doge-poducig del tumos 36 Q52 giotes ecepto blocke (RB) dibetc epopay,7 tcovusts,n dstal symmetc poyeuropty 8 depressants dsa symmec polyneropy,18 drec hormoe (H 9 defcency o 2425 excess o 28
esopve teapy n ge disese of one 71 Q0 ttyod drugs Grves dsease 4 paetc ypetydsm,42 sema sydome (},54 Q68 teolol tyotoxcoss 43 heoscleroc cardovsca dsese (CV} 6 tommue deis d pmry adena ue 36 ommue-meded type 1 diees mets,1 3 toomc europhy 18 B
Brarc srgery 8 Q9 �deocepors bockers r pheochmocytoms 333 �-lockers hyroid som etmet 9 hyrooxcoss 3 QO Bgaides,for dibees meitus O Blateal adea l emorge Q42 Bsphospotes ypeclcem,64 65 oseopoross 6869 Boe mne desty BM 6667 Q2 decle ,67 d cture rsk 67 cse . 66 mesrmen of,67 68 Bromocrpte fr procoms 26 C
Caergole Q8 for Cshg dsese,28 r procoms 26 Q19 Calciton, 2 osteopoosis 69 Caciol,62 66 Cacum homeostss d one physoogy 662 possrgc hypopryodsm ad suppemeno ake Q3 Cacum cbone ypocalcem 66 Caum ce n hypoclcem 66 Ccumcre cece ro 665 Caagoz r dees meus 10 Cpscn cem 18 Cadiovsclr dsese CV} diees mets d 1 67 6 Catecolmes 29 29 Ceac dsease,utommue-medated type dbetes and 3 Cetral dabetes spdus 225 Cet ypetyodsm 45 Cet ypotyodism,mesuemet o serum ee tyoxe (} level Q36 Clopopmde r detes mels O Clomphne cre 57 Q6 Couous gcose moong CM} 7 Q53 Couous scueos sn infso C} erpy 79 Coricorophin-reesg hormoe (CH} 19 28 Corisol,29 Crtc ness dren fco dg 3839 Cushg disese 2829 Cusg sydome C} 28 3032 causes o 30 30 , C del glds Q5 digoss o 3032 3,Q5 Q48 edogeous 30 trogec 30 Q23 mgg studes 3,32 ad pseudo-Cushg sydrome 30 treatme of 32 Cysc foss d nfeliy Q 137
Index
D
Dapagliflozi. or diabetes meitus, Ot enosmab n hyperclcema 65 n osteoporosis, 69 esmopressi cet diabetes isipds 25 Destructive thyroiditis44 Dexmetsoe i prmary adenl aire38t i secondry cortso deiciency 23 1-mg dexametasone sppresson estQ48 DHAi prmry adenl ire 37, 38t Diabetes mellts d coic kdney disease QSI clssiicatio o 1, 3t isl deciecy, 3 3 isl resistce, 35, 3t commo types, 3t, S complicatios o acte14 ! coic168 1 6t diagnostic criter . 1 2 eevted psm glucose leves i 1 isln terapy in basal d pradal isli, i hosptlied paiet Q47 tiig isses wit Q38 maageet o. 56. 6t blood glcose moitorng 7 7t noprmcoogc appoaches 78 ptiet edction 67 pracoogic terapy 8, t sceeg r 2t type 3 3t ( also Type 1 dabetes) type 2 4S ( also Type 2 diabees elitus) Dabetes sel mangemet edctio (DME) 67 Dabetes sel maagemet spport (DM)67 Dibetic myotophy18 Dabetic coplicaios d glyceic trgets Q4 Dibetic oot ces 8 Dabetic keoacidoss (KA) 3 14 Q24 Dabetic ephropthy16t, 1 Dabetic europty 6 1718. Q66 Dabetic retiopathy 17 Det ad exercise r preventio/delay o type 2 diabetes4t Dpeptdyl peptidase4 (P4) ihbiors r diabetes melits 9 t Dstal symmetric polyneuropaty (D N) 18 Dopamine goiss (DA)f prolactioms 26 Dgindced thyroid dyscton 46 47t Dual-eergy x-ry bsopiometry (DXA) sc 64, 67 Q2 Q43 Duloxeie i dibetc poyeropaty Q66 i dstal symetric polyeuropathy 8 E
pinephie29 pleeone pimry yperldosteronism 35 strogen gosts ad atgoistsor osteoporosis 69 strogen replaceme ypegonadotropic ypogondism 5455 tyroi sick sydome (), 48 Q3 xeatide or dibetes melits t ercise dibetes mageet. 8 ad hypoglycema 12 Q35 F
Familial hyperpyroidis d yperclcei 65 amilial ypocalcric yperclcei (FHH)6465 rie clcim d cretiie evels in esreet of, Q37 ' rm sig ypoglycemi 1 sig plasma glcose (PG) 2t, Q7 emae reprodctive disoders eorre 5455 eme nertilty, 5657 femle repodctio physiology o, 53, 3f yperdroges sydroes 5556 Fieeede spirio (A) 42 o y rod odles 51 S Q8 Fdrocoriso i pi dre ilre 38 Q4 Q82 id resscito, i ypercalceia65 ollclesimulating omoe (H) 19 9t, 53
138
Foot care i diabetic patiet18 Foot lcers i diabeic patient 8 Frctur Ris Assessmet Tool (AX) calclator 6768 rctres oseopooss and67 pedictio o rsk o 6768 Framgm is core 4 G
Gabapeti, i dstal symetic polyneropaty 18 Gesatoal diabetes mellitus, copicatios reted to S screeg r 5 therapy rS Gigatism 27 Glclader dabetes mell ts O Glmepride dbetes melts Ot Glpider dib etes elits Ot Glucago-like peptde (GLP-) mieticsor dibees melis 910 Glcocoticods hypercalceia 65 n lymphocytc hypophysitis 20 n priry drel ilure373838t Q82 n yroid stom tremet 49 Glucose metabolism dsorders o See also specif dsorde dibetes mellts, 111 yperglycem, 12 ypoglycemia 124 Glutaic acid decarboxylase (GA65) 1 Glybride r diabees elis, Ot Glycemic rgets nd diabetic compicatios Q4 Goiter 41 ltiodlar 5152 simple 52 Godotropi-poducig piitry deom s28 Goadotropirelesig hormoe (GH) 1953 Graves disease 4344 Graves opthalopty, 44 Q70 Growth oroe (GH), 19 deciecy o 4 excess o, 27 ( also Acromegaly) Gyecomasi, 606 cases o 6061 examiaion i, 6 H
Hashioto tyroidits d ypotyroids 45 Hemochromatoss diagosis o Q30 Hemodialysis hyperclcemi 65 Q75 Hemoglobin A testig 2t77 disadvantages o i ptiet with dibetes melits nd chroic kidey disese QSJ Hrstism, 5556 Hoeymoo phse isli eapy i 3 Huma corioic gonadotropi (HCG) tesig 55 Hydrocoisone e adrelectoy paie wt Cushng sydrome Q39 pmary adenl ire 38t, Q82 i secodary cortso deiciency 23 25Hydroxyvita D 61 62 Hyperadrogenism sydomes5556 Hypercalcema 6266 cses o 62 63 clnica etes o62 diagosis o6263f o-parathyrod hormoemediated 6 Q22 parathyroid ormone-n1eiate. 62-65
tremet of, 6566 Hypergycemi magement o hospitalied paients w diabetes melis 2 hospialed paients wiot dibetes melits 2 Hypergycemic hyperosmolr sydroe (HH)4 S Hypegoadotropic ypogonadism lneelter sydrome ad QS8 Hyperprolactieia 2527, 2t QOQ84 antipsychotcs and Q causes o 2526 2t ciicl etes d digosis 26 ad secod ry eorea 54 therpy r. 26
Index
Hyperthyodsm during pregnancy, QI subclinical 45 tiodothyone (T3 ) eve easeent o Q21 Hypocalcemia cinica eaues of 66 diagnoss and causes of 66 hypoparathyoids and 66 ow agesum eve and Q28 treamen o, 66 Hypogyceia and alered mea stas. Q20 defnto o 2 exercise-induced Q35 patets wih diaees eltus. 213 n patents wihout daees elius 3 dieenial diagnosis of 13 fsing hypogycea 3 postprandal hypogycema 3 n paent wthou diaetes meltus Q67 Hypogycemic uawaeness 18 reamen of, Q76 Hypogonads. 5759 andoge deciecy aging ae 5758 dese r fertiiy and theapy o Q32 evaluatio o 58 59f prmay. 57 seconday 57 estosteoe epacemet heapy 5859 60t Hypogonadoropic hypogonadism 54 GnRH deciecy and, 24 heochromaoss and Q30 Hypopaahyods ad hypocalcemia 66 possurgcal, Q34 Hypopitutars 2122 adrenocoicotropc horone decency. 2223 23 causes of 21 22 cenral diaetes nspds 2425 gonadotopin dececy 24 growth hooe deciency 24 pahypopiutaism 25 Sheeha syndome and, 22 thyodstmag homoe deciecy, 2324 Hypohalamic ameohea and GnRH dececy 24 Hypohalacptiayovaa axis 53 Hypohemia in myxedea coa. 49 Hypohyrod 44 Hypohyroids causes o 45 cenral Q36 evauao of, 45 management of 4546 medcaion nduced 45 i pregnacy Q41 Hyseosalpngogram (HSG) r uba patecy Q73 andonae, r osteopoosis 69 dopathic type 1 diaetes 3 ncidenally noed adrena ass 3940 39f QO Q60 nertliy feale 5657 mae, 60 nsul resistance 3 gestaiona dabetes metaolc sydroe 34 4 obesty ad, 3 type 2 daetes eius 4 nsulin herapy ype dabetes. 89 8t. Q63 Q83 See o Diabees ets ntrapeosa sins sapg (PSS) 28 odne deciency 41 odne dop in thyod sorm teaten 49 onze acum eve esg o J
Jod-Basedow phenoeno 44 K alan syndome ad GnRH decency 24 aryotype testng, Q58
eoacds diaec 3 14 t Q24 eoconaoe in Cushg disease 28 lnefeer syndome Q58 and pma hypogonads 57 L
Lacic acdosis 9 Lapaoscopc aenalecomy 35 Lase phoocoagulaion in dabeic etopathy 7 Lae auoimune diaees aduls (AA) 3 Laengh (N) saivay coso 3032 Letooe 5 Levohyoxne hypohyodsm 45 Q6 hypothyods fom puay dysncon and dosage o Q56 hypohyods n pegnancy Q4 Lfesye modfcaions. n diaees manageent 4 5 agip fr diaees elltus O pase inhbtos o peventon/deay o type 2 diaees 4 ragtde o daetes meius. IO hm and hypecacema. 65 oop duetcs in hypercalcemia 65 ow-os e exaehasone sppessio es (ST) 3031 40 ow rioohyoine (3) sydroe 48 uteinig homoe (H) 19 19 53 Q77 yphocytc hypophysts 20 yphocytc hyrois 40 M
Male epodcive dsordes anaoc eoid abuse 60 gynecoasa 6061 hypogoads 5759 ae nertiy. 60 mae eproducon. physology of, 57 57 Malgancyassociaed hypercalceia, 65 Mautyonse diaees of young (MDY) 5 Medca ntton therapy dabetes aageen 78 Mea thyod cace (MC) 53 pasa ractonated meanephne evels in Q74 Megiindes, for diabees elts Ot Mensta cyce 53 Menal sats changes hypoglycea and Q20 yxeema coa 49 Meabolc bone dsease 66 Meabolc sydroe 3 ad cadovasca dsease (CVD) 3 denon o 3 4 Endocrne Socey on sceeing for 4 and ype 2 dabees eis 3 0year CV sk calcuation o 4 Meon o ype 2 diabees. 4 9 O. Q29 Mehaoe Gaves ophhamopahy Q70 hyrooxicosis 43 Meoprolo. suacte hyoidts QIO Meyapone in Cushg disease 28 Mcoprolactinoas. in asympoac paens Q65 Mgto o diaees meltus O Mneaocricoi antagoist n piay hypeadosteons 35 Mneralocoricoids in piay adrena iure. 37 38 Mioane 40 Mixed meal oeance est, 13 Mutnoda goie 44 552 Mutpe day injection (MD) nsin theapy 7 8 Mutpe edocrie neopasa syndoe (M) 65 Mutple edocrine neopasa sydoe ype 2 (M2) Q2 Myxedema coma 49 N
aeginde o dabetes meius t aoal steopoosis Fodation on osteopoross evauaton 67 eve compession synomes. ohyoda lness syndome. 48 orepinepe 29 orocalcemic pary hypeparathyoids 64 0
ral glcose oeance est (G) . 2t risat r peveon/deay o ype 2 diaetes
139
Index
Osteonecrsis o jaw 8 Osteopenia. 6668 Se ct/so Osteoporois Osteoporsis annal reassessmt i. 69 BD tesing and DEXA scan 67-68. Q 2 Q3 boe minera densty los ad. 67. Q25 deed. 67 diagnosi o 6768 ypecoisolism and rik o Q43 Naional Oseoporoi oundation and Endocrine Socey recommedation. 70 physoogy ea ed to, 6667 risk assessm ad screeing gdenes. 67 67. 68t secondary caLse of 68. Q25 treatme o 68-69 veeba imagig 68 viamin D ad 69-70 Ovight bood glucose moong p
Pednisone n primary adenal ilure, 38 Q44 n econdary cortsol deciency. 23 Pegabalin n ds al symmetric poyeuropty 18 Pegancy diabets in. 5 tyoid unction and dsease ding, 6. Q hypotyodim n Q4 polactnoma i, 267 and secondary morrhea 5 tionamie e ding, 8 tyoid unction i. 6-48 8 visual fld tng during Q3 Premaure ovian inuf ciency (PO). 5 Peibia myedema. 43 Pimary adea ale. 36-38, Q82 causes ad clnical ates. 36. 37 dagnoss o. 36-37 prednison ad docortisone i. Q44 treatme o 338 38 Pimary amenorhea. 5. Q9 Pmry yperdoseoim (PA). 3-36. 3 5 Pimry yperparathyrodism. 626. 6. Q2 paratyoidectomy fr 63. Q7 nd vtamn dciency Q46 Prma hypogonadsm 57 Pmary hypothydsm and hyperproactnema 26 Pmary yrod lymphoma. 52, Q5 Pogeterone chaenge test. 55 Polactin. 19 Polactinoma. 25 i pregacy 2627 3 therapy or 26 Popraolo thyooxcoss. 43 Popythouracl (PTU) or hyperthyrodism duing pregnacy. Q fr hyrotoxcosis 43 PseudoCushng sydrome 30 Pseudogynecomta 61 Pseudohypercacema 61 Q3 Peudoypocalcemi 6
Page dsase o one 707 Q0 clincal manesation 0 7 dignosis of'. tetmet or 71 Pamidoae. r Paget dsease o bo. 7 Paypoptarism. 25 hormon replaceme theapy n. Q56 Paraggliomas 323 Paratyid carcinoma. 6 Paratyoidecmy. or primary ypeprahyoidsm 63 Q Paratyroid hormoe (PH). 61, 62 al ypercalcemi Paroxetine. i disal symmetric poyneuropahy 18 Pasreotde. i uhng disease. 28 Paten education or detes manageent. 6-7 Pegvisoma. 27 Phenoyenzamie o pheochomocyom 33 Q55 Pheocromocytoma. 3234. 32. 34 Q55 Q7 diagnosis of. 33 mtpe endocrne noplasa (MN) syndroms ad. 33. 33 radiogaphic oclition of 33 tratmt of 33-3 Physologc insulin terpy r ype I diabets. 89 8 Piogiazon. fo r diabes ml. 5. Piuiry adeoa '0. als Ptita tumos Piuitary popey. 222. Q Piuiary gad disorde aaomy ad physioogy eted o. 820. 9. 19t ypopttaism 21-25 piuiary hormone defciecy nd excess. testng fr. 9t piuitr hormone eces. 5-9 piuita tmors. 20-21. 20 Pittry tumors 20 empty sella 21 unctional. 25 ncidentally noted. 20 -21 macroadenoma. 20 2 mas eecs of 2 microadenoma. 20 nonnctioning, 2 sella mass. appoac to. 20 Plasma adosterone conceraion (PAC) , 3 35t Plasma adosterone-plasma rein actviy rao. Q71 Plasma fee metaephines measuement of Q50 Plasma reni acivty (PRA 3 35t Polycysic ovary syndrme (PCOS). 5 . 5556 Q6 elevted retng ueinig homone lvel n. Q7 estrgnprogestin ol contracepive pils in Q6 Q5
Sacoidosis, hypercalcemia n Q22 Saxagipi, diabetes melltu It Secondary amenorhea. 555 Secondary hypogodism. 57 Secondary hypotyodsm 2324 Sl moniorg of' lood glcose (SMG), Serum feritin level nd traserri sauraton measueme o Q30
Polyuria. hypercema nd 65
Sheehn syne hypptaris nd 22
Pooed ohot quaon . 16 Posmeopasa womn f racte rk n 6 osteoporosi rement n. 6 8-69 Postpartum tyridii Postpndil hyperglycemia Q69 in pregnacy. 5 Postprandia hypoglycemi Potassium cloride. n diaec ktoacdos Q24 Pramlinid for diaes melits 10 Predibs. I Predisolon i primary adral filure. 38
Saglptin. o r diaee melltus Smokng cessaion r peveniondeay o ype 2 diees. t Sodiumgucose rnpoer2 (ST2) hior. fr dee melitus. 9 t Somaotn anlogues. i acomegy 27 Spronoactone. n prmary hypeadoseoim 35 Q 9 Stereoacc rdogey. in acomegay. 27 Subclnica ypertyroidm. 45 Subclica ypohyroidim. 6. Q6 Sonylea diabetes melius t nd hypoglycemi. Q20 Sydrome o appropriate AD ecetion (SfAD 28
140
R
Radioaciv iodine baton !'or thytoxcoss 43 fr toic nodules 44 Radioacive iodine ptake (RAl). 2. QJ8 Raloifne r oseopoross. 69 Receptor actiao o c e cor K B (RA N) lgnd iibitos. osteoporosi. 6 9 Repagline. or dibees mlit. Reitant hypeension. Q1 Riedoate o oseopoosis. 69 o Paget disea se o bone. 71 Ripidone, and hypprolacinem Q Rosigiazone 'o diabees melitus. 0 pveion/deay o type 2 diete. 5 s
Index
T eriparatde, osepsis 69 ertay ypeparahydsm 64 esticular faie Primay ypgonaism essene eplacement theapy. 58-59 601 aze recs an hypecacema 65 hazolinenes for diabees melius, IO peventn/elay f ype 2 aees. 4 t inamdes n yroi srm eament 49 n yrtxicsis 43 yroglbulin (gAb) 42 yri autantidy measurement. 4 yoi cancer 5253 an ajuvan raiacive dine herapy, Q62 incence of 52 medullay 53 staging an pgnosis . 52 eament . 5253 ypes equency f 52 52 hyoidecmy, r sustea ge Q72 yid emegencies 48-49 hyid funcin, n pegnancy. 4648 48 hyd funcin es in eery paient, Q59 hyd glan anamy an pysiogy, 4-4 isrers f euyri sick synrme. 48 functna 42-46 in pregnancy 46-48 48f stuctual. 5-52 hyri cancers 52-53, 52 hyroiemergences48-49 unctn evauaton , 4-42 hmnes of, 4 hyro hmne eplacemen eapy 45 yri hmne teapy, n myedema coma. 49 yroiiis. 44 autmmunemedae ype I abees and. 3 estcve 44 Hasmt 45 panfu, 44 painess 44 postpaum, 44 subacue. QO yid ndules 55 eauain of 55. QS ineneede aspratin f. t QB isty an physical examinatin incdenally dscvere. O ypes f hyd pexiase P) 4 hydsimuaing hmne (H, 9 9t 4 eciency . 2324 in eldey paen Q59 hydstimuatng hmne-secetng ums 28 hyrodstimuating mmungbuins () auantdies 42 yr strm 48-49, Q33 agnsis 49 treamen 49 yrxicss, 42 evaluan . 42-43 managemen of 43 sympms o 4243 ypin receptr RAb 4 yone ( ) 4
ssue tnsutamnase aniby esting Q luamie for aees melitus O xic adenma 44 anssphenodal piuary ecompressn Q7 anssphendal umr resecn n acromegay 27 n Cusing dsease. 28 ansvanal ultasund shan syndme Q68 dothynne ( 4 Q2! ogiane, r peventindelay f ype 2 daees sce. 6 uer synme 54 ype iabees 3t Q4 o Diabees metus acuire 3 autommunemeiated, 3 iipahic 3 insun ecency an I herapy 89. t Q83 ype 2 aees meltus 4 Q29 s iabees mellius iagnss Q5 epdemgy 4 eilgy . 4 kesspne patens wth 4 Q6 metablc syndme an. 3 besty an 4 preventn/elay f, stategies fr. 4. t herapy f 9 Ot u
Ucers, t in iabeic patie 8 Urie abumn excretin eevaed. !6t, 7 24h urne fee csl (UF) 3 3 U Preventve evces ask Fc UP BMD esng an veebal magng, ecmmendans . 681 n seenng fr type 2 dabees. 21 V alpoae n sa symmec poyneupathy 8 enaxne n distal symmerc pyneurpathy 8 ertera actes stepoosis an 67-69 agipn r aees melus O ral necns an ype dabees meltus I isua el esting, 2 uring pregacy, Q3 itamin 6-62 hypecalcemia 62-66 hypcacma 66 prductn o 62f surces 6 iamin (ergcacrol) 6 iamin o; coecalcfeol 6 Q46 iamin ecency 69- Q gse. aees mells. ume epletn. hypecacemia 65 w
Weigh Jss or preventin ype 2 abees. 4 Wippe ra 3 Wf' ak eect 46 z
Zedrnc acd hypercacemia 65 o seporss 69 Page dsease one sce. 6
14
