Pathology – Endocrine Pathology by Pathology by Dr. Dr. Yabut
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elaboration elaboration of sufficient insulin to induce clinically significant hypoglycemia
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th e attacks consist princip principally ally of such such cent centra rall nervous system manifestations as confusio confusion, n, s sttup upor or,, and and loss of consciousness ; th e attacks are precipitated by fastin fasting g or exer exercis cise e and are promp promptly tly relie elieve ved d by feeding or parenteral administration of glucose
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Zollinger-Ellison Syndrome (Gastrinomas)
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Triad of: Recalcitrant pept peptic ic ulce ulcerr disease Gastric hypersecretion Endocrine ce cell tumor elaborating gastrin Ulcers: Duodenal and - Duodenal -
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smal l (often le less than 2 cm in diameter) encapsulated pale to redbrown brown nodul nodules es located anywhere in the pancreas Histo: look remark remarkably ably like like giant islets, with prese preservat rvation ion of the regular cords of monot monotono onous us cell cells s and and thei theirr orie orient ntat atio ion n to the vasculature. Immuno: insulin can be localized localized in the tumor cells EM: neoplastic β cells display distinctive distinctive round granu ranule les s that that contain polygonal or rectangular dens dense e crys crystal tals s separa separated ted from from the the enclo nclosi sing ng membra membrane ne by a distinct halo. Arise in th e duod duoden enum um and peripancreatic soft tissues, e.g., pancreas (gastrinoma triangle) 25% aris arises es in conjunction conjunction with other other endocr endocrine ine tumors MEN1 syndrome
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sis may re r esult fr f rom maternal diabetes, BeckwithWiedemann synd syndro rome me,, and rare rare meta metabo bolic lic disorders.
ratio
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Surgical removal but with recurrence
Pathology – Endocrine Pathology by Pathology by Dr. Dr. Yabut
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α cell tumors (Glucagonomas)
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Perian d postmenopausal women
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δ cell tumors
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VIPoma (Diarrheogenic Islet Tumor Cell) Pancreatic Carcinoid Tumors Pancreatic PolypeptideSecreting Islet Cell Tumors
Adrenal Cortex
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Associated with neural crest tumors rare
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rare
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gastri gastric c ulcers ulcers are often multiple Intractable to u su a l modalit modalities ies of therapy Occur in unusual locations, locations, e.g., jejunum Diarrhea presenting symptom in 30% of px 60% maligna malignant; nt; 40% benign Extremely high plasma glucagon levels Mild fe features of of DM Migratory necrotizing necrotizing skin erythema anemia High plasma somatostatin levels Features Features of DM, cholelithiasis, steatorrhea steatorrhea,, and hypochlorhydia Wa te ter y diarrh ea ea Hypokalemia achlorhydia serotoninproducing asymptomatic
multifocal histology a nd ultrastructure similar similar to normal inte intest stin inal al and and gastric G cells
Pathology – Endocrine Pathology by Pathology by Dr. Dr. Yabut
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A. Adrenocortical Adrenocortical Hyperfunction (Hyperadrenalism)
- Dx: measuring serum level of serum corticotrophin and determining urinary steroid excretion after administration of dexamethasone to suppress corticotrophin levels - Morphology: depends on the cause Pituitary – Crooke hyaline change with basophils caused by • elevated glucocorticoid levels Diffuse Adrenal Cortical Hyperplasia – glands are • enlarged and affected bilaterally Nodular Adrenal Cortical Hyperplasia – cortex between • nodules is identical to diffuse hyperplasia Adenomas – small, well circumscribed • •
Carcinomas – larger, unencapsulated
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Zona reticularis and fasciculate – atrophic (both the adjacent and contralateral) Incidence Clinical Features
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Hypercortisolism (Cushing Syndrome) -
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Cushing Dse
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Zona glomerulosa – intact Clin Clinic ical al Featur atures es:: Central obesity Moon facies Weakness and fatigability Hirsutism Hypertension Plethora Glucose intolerance/diabetes Osteoporosis Neuropsychiatric abnormalities Menstrual abnormalities Cutaneous striae Delayed wound healing/bruisability
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• • • • • • • • • • • •
Morphology
Pathogenesis/Etiol ogy
Lab Finduings
Primary Adrenal Neoplasms (Adrenal adenoma, CA, primary cortical hyperplasia) 10-20% of Independent of Px with unilateral endogenous corticotrophin neoplasm: Cushing because th e contralateral syndrome a dr dren al als fx n adrenal cortex is autonomously Adults: atrophic vecause aden adenoma omas s and of costicotropin carcinomas suppression Children: and low levels of carcinomas corticotropin Ectopic Costicotropin Secretion by Non-Pituitary Tumors Tumors 10% of Adrenals are Associated Associated with endogenous bil at ateral a nd nd smal smalll cell cell CA Cushing hyoerplastic of the lungs syndrome - Rarely Men, 40 40-60 y/o associated associated with ectopic secr secret etio ion n of corticotrophin -releasing factor Young adults Adrenals are Elevated 7 0-80% of bilaterally serum F:M 5:1 endogenous hyperplastic corticotro hypercortisolism
Treatment
Pathology – Endocrine Pathology by Pathology by Dr. Dr. Yabut
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Primary Hyperaldosteronis m Characterized by - Characterized chroni chronic c exce excess ss aldosterone secretion Na rete retenti ntion on and K excretion HPN and hypokalemia
Women ag aged 30 3050 y/o
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Asoociated Asoociated with a corticotrophi corticotrophinnproducing pituitary adenoma Hypokalemia weakness, paresthesias, visual disturbances, tetany Na retention retention increas increases es total total body Na and ex pa pands E CF CF volume hypertension
pin
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Adrenogenital Syndromes - Androgen-secreting adrenal cortical neoplasms: androgensecreting adrenal CA Congenital adrenal hyperplasia (CAH): autosomal recessive o metabolic errors characterized by a deficiency or total lack of a o particular enzyme involved in the biosynthesis of cortical steroids, i.e., cortisol steroidogenesis is channelled into other pathways increased o production of androgens virilization 21-hydroxylase deficiency Defective conversion of progesterone to 11o deoxycorticosterone by 21-hydroxylase (CYP21B)
Solitary, small, encapsulated adenomas occur occurri ring ng more more commonly commonly on the left side May be buried w/in the adrenal adrenal gland land and and not not apparent externally Cut Cut s su urf rfac ace e is bright yellow high lipid content Lipid l ad aden c el ells resemble resemble cells of zona fasciculate Presence of PASreactive, eosinophilic, laminated, cytoplasmic inclusions inclusions known as spironolactone bodies 3 distinct o
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Autonomous overproductio overproduction n of aldosterone caused by: Conn syndrome Idiopathic hyperaldoster onism Gluc oc ocor ti ticoi d -remediable hyperaldoster onism
syndromes: Salt-wasting adrenogenitalism adrenogenitalism Simple virilizing adrenogenitalism without salt-wasting Nonclassic adrenogoenitalism
Morphology: Substantial, bilateral adrenal enlargement o Widened cortex and nodular o Appears brown because of lipid depletion o
Pathology – Endocrine Pathology by Pathology by Dr. Dr. Yabut Adrenomedullary dysplasia – incomplete migration of the chromaffin cells to the center of the gland Clinical features Determined by specific enzyme deficiency o Abnormalities related to androgen excess vs. o aldosterone and glucocorticoid deficiency CAH – any neonate with ambiguous genitalia o Severe enzyme deficiency can be life-threatening o with vomiting, dehydration, and salt-wasting Women may present with delayed menarche, o oligomenorrhea, or hirsutism o
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