Medical Endocrinology PDF

127 ❖ DO NOT use this anticoagulant ❖ Cirrhosis for any enzyme analysis- may ❖ Viral hepatitis inhibit activity...

127 ❖ DO NOT use this anticoagulant ❖ Cirrhosis for any enzyme analysis- may ❖ Viral hepatitis inhibit activity b. Impaired renal function ❖ Blood urea is ♦ (,t- excretion into 5. BUN/creatinine ratio is normally about intestine, site of conversion to 10:1-20: 1 ammonia) CYSTATIN C 1. Serum marker for GFR 5. Causes of false ,t. due to specimen collection and handling 2. Small protein produced by most a. Failure to place sample on ice, nucleated cells in a consistent manner, centrifuge and analyze immediately unaffected. by inflammation, gender, (nitrogenous constituents will age, eating habits, or nutritional status metabolize to ammonia) 3. Method= immunoassay b. Poor venipuncture technique URINE ALBUMIN (probing) c. Incompletely filling collection tube 1. Units a. 24 hr collection: mg albumin/24 hrs b. Random sample: mg albumin/ gram creatinine 2. Alhuminuria categories Category Urine albumin Term Specimen Collection for mg/24hr or mg/g creat. Ammonia Analysis A1 < 30 N to mild,+.. A2 30-300 Moderate ,+.. Endocrinology A3 > 300 Severely ,t.. GENERAL 1. Hypothalmus / Pituitary / End Organ URIC ACID System- Hypothalmus produces 1. End product of purine metabolism releasing hormone which stimulates pituitary to produce stimulating 2. ♦ in gout, renal failure, leukemia, and hormone that causes end organ to chemotherapy treatment produce hormones or initiate a process 3. Colorimetric method (see table page 128) a. Uric acid reduces phosphotungstic 2. Hyper and hypo conditions: end acid to tungsten blue measured product hormone is ♦ (hyper) or t spectrophotometrically (hypo) b. Interferents include lipids and a. Primary caused by end organ several drugs problem b. Secondary caused by pituitary 4. Enzymatic assays are based on the problem uricase reaction in which allantoin and c. T ertiary caused by hypothalmic H 2O2 are produced and H 2O2 is problem coupled to give a colored product AMMONIA 3. Regulation - end organ product or process feeds back to hypothalmus and 1. Derived from action of bacteria on pituitary to stop production of contents of colon r eleasing and stimulating hormones 2. Metabolized by liver normally THYROID HORMONES 1. Stimulate metabolic processes; 3. ,t. plasma ammonia toxic to the CNS necessary for normal growth and 4. Hyperammonemia ( ♦ ammonia) development a. Advanced liver disease (most 2. In the tissues T 4 is converted to T 3 common cause) (physiologically active product): T4 ❖ R eye~syndrome concentration much higher than T3 128 a. 99.97% of T 4 hound to thyroxine- d. Hashimoto's Thyroiditis binding globulin (TBG) ~thyroxine- ❖ Thyroid aut·oantibodies binding prealbumin (TBPA) and ❖ Lab findings aUmrnin; 0.03% is free 1& t T3 and T4 b. T3 is 99.5% bound and 0.5% free 1& ,t.. TSH 3. Only free fractions metabolically active; 6. Tests for Thyroid Function bound is for storage and transport a. TSH ❖ Ultra-sensitive immunoassay 4. Primary hyperthyroidism (t TSH; ❖ Single best thyroid fu11ction test -t- T4andTy b. Total thyroxine (T,i) a. Symptoms include weight loss, heat c. Free T4 intolerance, hair loss , nervousness, d. (Direct) T 3 measures tachycardia and tremor b. The most common cause is Grave's triiodothyrinine (T3) disease e. T3 uptake ❖ Autoimmune disorder ❖ Indirect measuremfmt nf TRG ❖ Antibodies to thyroid-stimulating ❖ No longer recommended hormone (TSH) receptors ADRENAL CORTEX HORMONES ❖ Causes thyroid hyperactivity and 1. Hypothahnus produces CRH that suppression of TSH stimulates pituitary to produce ACTH ❖ Lab findings that stimulates adrenal cortex to i& Normal or ,t.. T 3 and ,t.. T4 produce steroid hormones made from i& t TSH cholesterol c. Pregnancy 2. 3 classes of steroids produced ❖ TSH first trimester a. Mineralcorticoids ❖ TBG due to estrogen ❖ Aldosterone ❖ FT4 and FT3 t second and third b. Glucocorticoids trimesters ❖ Cortisol ❖ Total T4 and T3 ,t.. c. Sex hormones 5. Primary hypothyroidism ( t T 4 and T3. ❖ Androgens: testosterone ♦ TSH) ' ❖ Estrogens: estradiol a. Symptoms include fatigue, weight 3. Regulation - cortisol feedback to gain, decreased mental and physical hypothalmus and pituitary to stop output, cold intolerance production of CRH and ACTH b. Cretinism - congenital ALDOSTERONE c. Myxedema - sever e thyroid deficiency in adults 1. Maintains blood pressure, promotes sodium r eah sorption and potassium secretion in distal tubles and collecting ducts of the nephron HYPOTHALMUS / PITUITARY/ END ORGAN SYSTEM HYPOTHALMUS PITUITARY END ORGAN PRODUCT/ ACTION TRH TSH Thyroid T4 andT3 (thyrotropin releasing hormone) (thyroid stimulating hormone) CRH ACTH Adrenal Cortex cortisol, aldosterone, (corticotropin releasing (adrenocorticotropic releasing estrogens, testosterone hormone) hormone) GnRH LH Ovaries ovulation (gonadotropin releasing (leutinizing hormone) m OR hormone) AND Testes sperma togenesi s FSH (follicle stimulating hormone)  129 REMEMBER! The Thyroid Sisters Morbid Matilda Everything __ Myxedema is racing (,I. T3 & T4) Everything is EXCEPT low (t T3 and my TSH (t) T4 ) except my TSH (+) 2. Regulation of secretion through renin- and hypertension angiotensin system b. Truncal obesity, facial hair, a. Renin converts angiotensinogen to 11 buffalo hump 11 , osteoporosis, scant angiotensin I which is rapidly menses converted to angiotensin II which stimulates cortex to produce 3. t cortisol - Addison1s disease (see aldosterone Aldosterone) 3. Hyperaldosteronism (,t. aldosterone) - ANDROGENS Conn's Disease 1. Male sex hormones, secondary sexual a. ,t. Na+ characteristics b. t K+ c. Hypertension 2. Secreted by testes, adrenals and ovaries 4. Hypoaldosteronism (t aldosterone) - Addison's disease 3. ,t. testosterone - precocious puberty in a. tNa+ and c1- boys , testicular tumors; masculinization in females b. tcortisol c. t hemoglobin 4. t in hypogonadism d. t urinary steroids 5. 17-ketosteroids (17-KS) e. ,t. ACTH when primary a. Metabolites of androgens hypoaldosteronism (adrenal cortex b. Zimmermann reaction problem) ❖ 17-KS react with metadinitro- f. t ACTH if secondary (pituitary) or benzene in alcoholic alkali tertiary (hypothalamus) problems ❖ Produces red-purple color ESTROGENS CORTISOL 1. Functions 1. Female sex hormones a. Causes ,t. glucose through 2. Secreted by ovaries gluconeogenesis and decreased a. Estradiol - secondary sexual carbohydrate use characteristics b. Inhibits protein synthesis b. Estrone - metabolite of estradiol c. Immunosuppressive and anti- c. Estriol inflammatory ❖ ,t. during fetal development in 2. ,t. cortisol ( without diurnal variation) - pregnancy ❖ Steady increase should occur in Cushing1s syndrome t a. Diabetes mellitus, plasma protein the third trimester 130 ❖ 24-hour urinary maternal estriol 3. Aldosterone monitors integrity of feto- a. ,t.. in upright position. placental unit ❖ Decline or sudden change 4. Renin indicates a complication of the a. Produced in kidneys; may draw from either renal vein pregnancy b. Tests 3. ,t. estrogen - precocious puberty in ❖ Renin activity (angioten sin I girls, feminization in males, pregnancy, generation) oral contraceptives, polycystic ovary ❖ Direct renin (immunoassay for disease renin molecule) c. Very unstable (sample must b e TESTS FOR ADRENAL CORTEX FUNCTION frozen immediately) 1. Cortisol d. ,t.. in upright position a. Diurnal variation (highest in e. t in Conn's morning) b. Can measure free (unbound) or 5. ACTH total in serum, plasma or urine a. Distinguishes between primary and secondary hyperaldosteronism 2. Dexamethasone suppression a. Give dexamethasone to suppresses 6. Testosterone cortisol production a. H ypothalmus / Pituitary / T estes b. Measure cortisol and/or Adrenal Cortex c. Interpretation b. Used for infertility testing ❖ Cortisol t (s uppressed) = normal ❖ Males: t causes infertility ❖ Cortisol ,t.. (not suppressed) = ❖ Females: ,t.. causes infertility, Cushing's birsutism , masculinization ❖ Cortisol partially suppressed = 7. Estrogens depression , obesity, pregnancy, a. Measure estradiol and/or estriol in stress, infection serum and urine REMEMBER! The Steroid Brother Cushy Carl C_g_shy's (Cushing's Disease) problem is everything is Anemic Addison yp: (Addison's Disease) ,t. cortisol, ,t. glucose Addison's problem is (Twinkies™ ), everthing is down: tcortisol ,t. Na+ (chips) t cortisol, turinary ,t. urinary t Na+ and c1- (needs salt), Steroids steroid---s- - t t Hb (anemia), ALD, and t Aldosterone (toilet), and t urinary steroids t Hemoglobin ♦ ALD Adapted w/111 Pe,m;ssion from Sylvia Rayfield &Associates  131 ADRENAL MEDULlA HORMONES : CATECHOLAMINES GASTROINTESTINAL HORMONES 1. Produced in chromaffin cells 1. Gastrin - ♦ in Zollinger -Ellison a. Epinephrine, norepinephrine and syndrome (p eptic ulcer s, excessi ve acid dopamine secretion) b. Homovanillic acid (H VA) = metabolite of dopamine 2. Serotonin c. Metanephrines and vanilylm.andelic a. Vasoconstrictor found in platelets, acid ( VMA.)= epinephrine brain and other tissue metabolites b. Increased produc tion in tumors of chromaffin cells of GI tract 2. Pheochromocytoma c. Measure breakdown product, a. Tumor of adrenal medulla 5-hydroxy-indole-acetic acid (5- b. H ypertension , headache HIAA), in urine d. 5-HIAA falsely ♦ from some drugs 3. euroblastoma - fatal tumor in or diet that includes bananas, children pineapples and chocolate 4. Tests for catecholamines TUMOR MARKERS a. Ca techolamines (plasma and/or 1. Most u seful application of tumor urine) markers is monitoring the course of a. Me tanephrines in urine best scr een treatment. for pheochromocytoma because 2. Common tumor marker s and their catecholamine r elease is r elated cancers (see Immunology intermittent and Serology Chapter) b. VMA - urine c. HVA - urine REMEMBER! Adrenal Medusa (Medulla) guards victims from the lion's D. E. N. in the Catacombs (Catecholamines)