Endocrinology Notes

CLINICAL CHEMISTRY ENDOCRINOLOGY Scope: 1. Study about endocrine glands – ductless glands that secrete hormones directly poured into the bloodstream 2. Study of hormones – chemical messenger; transmit messages to the brain 3. Study of various actions of hormones (stimulate/activate target organs) HIERARCHY OF ENDOCRINE GLANDS: 1. Hypothalamus - Controls all glands - “Master Gland” 2. Pituitary Gland - With 2 regions:  Anterior Pituitary  Posterior Pituitary 3. Grass Roots level of endocrine glands HYPOTHALAMUS - Secretes various hormones that control pituitary gland Hormones secreted: 1. CRF (corticotropin releasing factor)/ CRH (corticotropin releasing hormone)  Stimulates the pituitary gland on order to secrete ACTH 2. TRF (thyrotropin releasing factor)/ TRH (thyrotropin releasing hormone)  Stimulates the pituitary gland on order to secrete TSH 3. GnRF (gonadotropin releasing factor)/ GnRH (gonadotropin releasing hormone)  Stimulates the pituitary gland on order to secrete FSH, LH, & ICSH 4. PRLRF (prolactin releasing factor)  Stimulates the pituitary gland on order to secrete prolactin 5. ADH (anti-diuretic hormone)/ Vasopressin 6. Oxytocin PITUITARYGLAND 2 Regions: 1) Posterior Pituitary Gland – stores vasopressin /ADH and oxytocin 2) Anterior Pituitary Gland – secrete various hormones

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FSH – follicle stimulating hormone TSH – thyroid stimulating hormone ICSH – interstitial cell stimulating hormone ACTH – adrenocorticotropic stimulating hormone GH – growth hormone LH – luteinizing hormone PRL – prolactin

HYPOTHALAMIC HORMONES (Before, ADH and oxytocin were believed to be synthesized in the posterior pituitary, now they are synthesized in the hypothalamus and stored by the posterior pituitary) 1. ADH  Function: to prevent loss of body water/ antidiuresis via urine excretion  Deficiency: Diabetes insipidus  Excessive urine excretion (polyuria)  3L/24 hours  Pale color/colorless urine  Low specific gravity = dilute urine  Negative for glucose *Diabetes mellitus – deficiency of insulin; (+) for glucose 2. Oxytocin  Function: Promotes contraction of the uterus; stimulates labor PITUITARY HORMONES Pituitary Gland – secretes most hormones 1. TSH – stimulates thyroid gland in order to secrete T3 and T4 (thyroid hormones) 2. FSH 3. LH – stimulate corpus luteum 4. GH – stimulates growth 5. ACTH – stimulates adrenal cortex in order to secrete cortisol or aldosterone 6. PRL – stimulates mammary gland for the secretion of mother’s milk GRASS ROOTS LEVEL ENDOCRINE GLANDS 1. Pancreas  Secretes insulin, glucagon, and somatostatin

CLINICAL CHEMISTRY a) Insulin - Produced by Beta cells of pancreas - Lowers blood glucose - Promotes glycolysis and gluconeogenesis in the liver b) Glucagon - Produced by alpha cells of the pancreas - Increases blood glucose - Promotes glycogenolysis (breakdown of glucagon) c) Somatostatin - Produced by delta cells of the pancreas - Maintains optimum level of insulin and glucagon 2. Thyroid  Secretes T3 and T4 for the metabolism of food 3. Stomach  Secretes Gastrin  Gastrin – manufactures Hydrochloric acid/HCl; reason why gastric juice has a pH of pH 1-2 (strongly acidic); for digestion of carbohydrates 4. Intestines  Secretes VIP (vasoactive intestinal peptide) - responsible for motility of the intestines (peristaltic movement/motility) 5. Kidney  Secretes erythropoietin/EPO for RBC production  Secretes active vitamin D3 for calcium absorption from the food (Calcium metabolism) 6. Adrenal Cortex  Secretes Cortisol  involved in gluconeogenesis (amino acids, fatty acids, glycerol glucose)  called “glucocorticoid”  Metabolism promoted: Gluconeogenesis  Secretes Aldosterone  involved in reabsorption of sodium (the most abundant mineral/cation in blood)  called “mineralocorticoid”

Endocrinology 7. Adrenal Medulla  Secretes catecholamines (amino acid hormones) a) Epinephrine/Adrenaline – stress hormone b) Norepinephrine/noradrenaline c) Dopamine 8. Testis  Secretes Testosterone (most active of all hormones) 9. Ovary  Secretes Estrogen and Progesterone  3 types of Estrogen: a. Estrone/ES-1 – present in all in minute concentration; in young people/non-menstruating b. Estradiol/ES-2 – in menstruating women; responsible for growth and thickening of the endometrium; most abundant estrogen in premenopausal women c. Estriol/ES-3 – in pregnant women; gives nourishment to the fetus d. 10. Placenta  Secretes HCG (human chorionic gonadotrophin) PROBLEMS: Problem# 1: Low concentration of glucose Hypothalamus: secretes CRF/CRH  Stimulates pituitary gland to produce ACTH  ACTH will stimulate adrenal cortex  secretion of cortisol  gluconeogenesis (amino acids, fatty acids, glycerol →glucose); Problem# 2: Low T3 and T4 in the bloodstream Hypothalamus: secretes TRF/TRH  Stimulates pituitary gland to secrete TSH  TSH will stimulate the thyroid gland  secretion of T3 and T4  enhanced metabolism of food CLASSES OF HORMONES 1. Peptide Hormones - Majority of hormones - Derived from proteins

CLINICAL CHEMISTRY -

Ends in “in” and others Ex: insulin, gastrin, PTH (peptide hormone) Properties:  Soluble in water  Can circulate freely in the bloodstream  Do not require carrier proteins

2. Steroid Hormones - Derived from cholesterol (derived lipid) - Have “st” in their names - All sex hormones are steroid hormones Properties:  Insoluble in water  Cannot circulate freely in the bloodstream  Requires carrier/transport proteins 3 classes of steroid hormones: a) Sex hormones  Male: Testosterone – most active of all sex hormones  Female: Estrogen, Progesterone b) Cortisol – “Glucocorticoid” c) Aldosterone – “Mineralocorticoid”  “corti” – secreted by adrenal cortex 3. Amino Acid Hormones - End in “ine” A. Thyroxines a) T3 With 3 iodine atoms located in C3, C5, C3’ Name: 3,5,3’ – triiodothyronine 10% only b) T4 4 iodine atoms located in C3, C5, C3’, and C5’ Name: 3,5,3’, 5’ – tetraiodothyronine 90% *difference of T3 and T4: one iodine B. Catecholamines a) Epinephrine/Adrenaline b) Norepinephrine/Noradrenaline c) Dopamine *Catecholamines undergo metabolism in the liver and become Metanephrine *Metanephrine is completely metabolized and DNA goes out of Urine

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DNA: VMA (Vanillylmandelic acid) – metabolite of catecholamine used in diagnosis of phaeochromocytoma  Phaeochromocytoma - in adrenal medulla (passageway of urine; persistent tumor) - Symptom: Hypertension

4. Fatty Acid Hormones  Prostaglandin – only fatty acid hormone THYROID HORMONES - Synthesized by the thyroid gland - T3, T4, and rT3 (reverse T3; no proven hormonal activity; <1%) THYROID PROFILE - Test to evaluate the thyroid function/ thyroid activity 1. T3 2. T4 (Test for thyroid activity) – to know if there is:  Euthyroidism – normal thyroid activity  Hypothyroidism – low thyroid activity; below the reference range  Hyperthyroidism – high thyroid activity; above the reference range HYPERTHYROIDISM HYPOTHYROIDISM high T3 and T4 low T3 and T4 Fast rate of food slow rate of food metabolism metabolism Body weight reducers Body weight gainers Heat energy liberated: High Tolerance: Heat intolerant High mental and physical output Tachycardia and tremors #1 cause: Grave’s disease Grave’s disease – toxic diffuse goiter; enlarged thyroid; overactivity of thyroid gland

Heat energy liberated: low Tolerance: Cold intolerant low mental and physical output

Common causes: Cretinism and Myxedema Cretinism – congenital deficiency of thyroid hormone

CLINICAL CHEMISTRY Synthesis of Thyroid Hormones:  Step 1. Trapping of iodine content of food by the thyroid  Step 2: Iodination. Iodine ions inserted into tyrosine ring forming monoiodotyrosine/MIT (1 iodine atom inserted) or diiodothyrosine/DIT ( 2 iodine atoms) *Tyrosine – amino acid backbone of thyroglobulin (Thyroglobulin -precursor of protein of T3 and T4)  Step 3: Condensation and Complexation. Combination:  MIT and DIT = T3  DIT and DIT = T4  Step 4. Release of T3 and T4 into the blood circulation  Step 5. Transport of T3 and T4 in the blood circulation by proteins 

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T4    T3 

70% - transported by TBG (Thyroxine Binding Globulin) 20% - transported by Albumin 10% - transported by Pre-Albumin

70% - transported by TBG (Thyroxine Binding Globulin)  30% - transported by Albumin *Main function of T3 and T4: Food Metabolism Neonatal Hypothyroidism:  Hypothyroidism – underdeveloped brain (not properly nourished)  May lead to mental retardation  IMPORTANT: Newborn Screening Act (RA 9288) o Specimen: Dry blood spots (from heel) o Neonatal screening involves measurement of TSH and T4 (T4 is a requirement for food metabolism  inadequate nutrients  malnourished  mental retardation) o T3 is not tested because Hyperthyroidism has no significant effect  Treatment: Inject T3 and T4

Endocrinology HYPOTHYROIDISM: 1. Primary Hypothyroidism - Low T4 due to thyroid failure 2. Secondary Hypothyroidism - Low T4, no thyroid problem; Pituitary failure *TSH – test for pituitary gland; to know what class of hypothyroidism 3. Tertiary Hypothyroidism - Low T4, no thyroid and pituitary problems; Hypothalamic failure Sample problems: Q: T3 and T4 are low, TSH is markedly increased  Primary hypothyroidism Q: T3 and T4 are high, normal TSH level  Hyperthyroidism 2 CLASSES OF HYPERTHYROIDISM: *T3 – to know the level or class of hyperthyroidism 1. T4 Thyrotoxicosis – T4 is high, T3 is within range or low 2. T3 Thyrotoxicosis – T3 is high, T4 is within range or low HORMONE MEASUREMENT IN THE SERUM: 1. Bioassay – using alive laboratory animals Ex: Frog test  Pregnancy test to detect if HCG is present in urine (HCG – marker of pregnancy)  Uses male frog (inject urine of pregnant woman  appearance of sperm cells of the male frog indicates the presence of HCG) 2. Immunoassay (Serologic Tests) – detects immune complex (Antigen-Antibody complex) Ex: HCG and Anti-HCG antiserum  Uses Anti-human Globulin (to form bridges)  Labelled Different labels: a) Enzyme  Assay: Enzyme Immunoassay (EIA)  Ex. Horse radish peroxidase, ALP + dye

CLINICAL CHEMISTRY Will form a Colored solution Measured spectrophotometrically (instrument: Spectrophotometer) b) Radioactive isotope  Assay: Radioimmunoassay (RIA)  End result: emission of gamma particle  Instrument: Scintillation counter c) Fluorescent Dye  Ex. FITC (Fluorescein isothiocyanate)  End result: brilliant green fluorescence  Instrument: Fluorescence microscope  

3. Colorimetric reaction – old method a) Zimmermann Reaction  Detects 17KS (17 Ketosteroid)  Color reagent: m-dinitrobenzene  Colored product: Brown solution b) Porter Silber Reaction  Detects 17KGS (17 Ketogenic steroid) / 17OHCS (17 Hydroxycorticosteroid)  Color reagent: Phenylhydrazine and Sulfuric acid (H2SO4) c) Kober Reaction  Detects Estrogen (all women), Estradiol (Menstruating), or Estriol (pregnant) *absent Estradiol - menopause  Color reagent: hydroquinone Sulfuric acid  Read absorbance at specific wavelength DISEASES:  Phaeochromocytoma and Neuroblastoma – associated with catecholamines  Intestine – serotonin  Ovary – Estrogen  Placenta – Beta HCG  Avoidance of banana, chocolate, coffee, tea, and specially vanilla – VMA  Cushing syndrome – accompanied by hypercortilism (Hypercortisolism)  Addison’s disease – accompanied by hypocortilism (Hypocortisolism)  Zollinger Ellyson Syndrome – oversecretion of gastrin; hyperacidity

Endocrinology Pancreatic cholera (Intractable diarrhea) – associated with vasoactive intestinal peptide/VIP Carcinoids:  Hepatoma – liver cancer  Multiple myeloma – cancer of the bone marrow  Phaeochromocytoma – cancer of the adrenal medulla  Argentaffinoma – cancer in the small intestine 

Wrong pair: Hirsutism (excessive hairiness) and serotonin (hirsutism is a medical condition that can arise from excess male hormones called androgens, primarily testosterone)