![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
liveonearthWINTER 2009 FINAL EXAM STUDY GUIDE
I. Thyroid
1. Be familiar with specific thyroid hormone synthesis: feedback/role of TRH, TSH, tyrosine, iodine, percentage of T4 & T3 released by the gland.
2. Know what proteins function as thyroid hormones carriers?
3. How might changes in TBG affect Total T4 & T3 levels? What can alter TBG levels?
4. Why is total T4 NOT the best test to evaluate thyroid function?
5. Know the normal percentages of Free T4 & free T3 and their biologic activity?
6. Know how variations in TBG levels influence T3RU [See the TBG bus diagram. Be sure you understand what the T3RU uptake test actually measures!]
7. What does the FTI test measure?
8. Recognize hypErthyroidism vs hypOthyroidism (1o, 2o & 3o) from data provided. When would you want to use the TRH stimulation test?
9. Know how to use the FT4 or FTI to sort out TSH abnormalities.
10. What test would confirm a diagnosis of T3 toxicosis?
11. Why might patients with “Euthyroid Sick Syndrome” have hypothyroidism symptoms & what test would confirm your suspicion?
12. When would you want to order a radioactive iodine uptake test, or a thyroglobulin level? What other test do you need to order simultaneously?
13. What TSH & FT4 levels and antibodies are typically present in Graves Disease & Hashimoto’s thyroiditis?
II. Liver and Hepatitis
1. Know why the enzymes on a hepatic panel are not necessarily good indicators of liver function and what tests are better indicators of liver function?
2. What disease process is suggested when an increased ALP is greater than the increase in AST or ALT, and vice versa? How would you verify that an increased in ALP originated in the liver?
3. Know the various interpretations of the AST/ALT ratio.
4. Know how the prothrombin time (PT) as a prognostic tool in chronic liver dz.
5. Know whether the cause of jaundice is pre-hepatic, hepatic, or post-hepatic based on the patterns of conjugated & unconjugated bilirubin in serum and urine.
6. What tests are included on a typical “acute hepatitis panel?” Why doesn’t the panel include testing for HDV, HEV, or HGV?
7. What degree of elevation in AST & ALT typically occurs in acute hep? Why might unconjugated & conjugated bilirubin increase in acute hepatitis?
8. What test would confirm acute Hep A? Acute Hep B? What tests are used to confirm Acute Hep C? What must you do if the confirmatory tests are positive?
9. What’s the clinical significance of a positive HBsAg test? How do you distinguish between acute & chronic Hep B in a person with a “+” HBsAg test?
10. Know the order of appearance of the various antigens & antibodies in a person who recovers from Hepatitis B.
11. Know the pattern for a person who develops chronic Hepatitis B and how to distinguish the replicative from the non-replicative states. Be familiar with HBV testing summary slide. How is chronic Hep B defined?
12. What is the “core window?” What tests will be positive during that period?
13. When might you want to screen for Hep C Virus? What is the significance of a positive Hepatitis C Virus ELISA test and a negative RIBA test?
14. What’s the significance of a positive Hep C Virus ELISA test & a negative qualitative HCV RNA test?
15. What test would monitor the effectiveness of anti-viral therapy in a confirmed chronic Hep C patient? Why is it advisable to do HCV genotyping in this patient?
16. When might you order the Hep D virus? Understand the difference between co-infection & super-infection for HBV & HDV and their respective test patterns.
17. When might you decide to test for the Hepatitis E virus? (postabsorptive)
III. Endocrine: Parts 1 and 2
1. How would you optimally instruct your patient to prepare for an OGTT?
2. What happens to blood GLUC and K if you don’t separate RBCs from serum promptly?
3. Know: Adult FBS, 2-Hr postprandial & 2-Hr GTT criteria for diagnosing diabetes, impaired fasting glucose & impaired glucose tolerance.
4. Be familiar with the endocrine interpretation of OGTT. How would adrenal fatigue affect the outcome of a 5-hour OGTT?
5. What are the current criteria to dx reactive (post-prandial) hypoglycemia?
6. What are the indications for performing an insulin assay?
7. When combining OGGT & insulin tests, what patterns would you find with IDDM, IGT, & NIDDM? Why might Cushing’s Synd. predispose one to high insulin levels?\
8. What level of HgbA1c is considered evidence of good diabetic control? How often should the test be repeated? Is A1c useful for brittle diabetics?
9. Know cortisol & ACTH patterns for Cushing’s Syndrome vs. Dz, & Addison’s Dz. What test is useful to screen for Cushing’s Syndrome?
10. How might Cushing’s Syndrome & Addison’s Dz influence test results on a Basic Metabolic Profile? Be able to predict the effect of excess cortisol on thyroid gland function.
11. What is the Dexamethasone Suppression test used to dx?
IV. Endocrine Part 3: Menstrual Cycles
1. What is the significance of low estrogen levels during the follicular phase of the cycle?
2. What is the significance of elevated estradiol levels in males?
3. How do estrogen levels influence secretion of LH? How do the LH & FSH levels differ in primary & secondary hypogonadism? In infertility?
4. How do FSH & LH levels change after menopause? At what point of a “normal” menstrual cycle would FSH & LH levels be the highest?
5. What are the indications for testing progesterone? How do the levels change over the course of a “normal” menstrual cycle? What happens to progesterone production in anovulatory cycles?
6. What are the effects of increased Prolactin levels? What difference in prolactin levels might be seen between nursing & non-nursing mothers?
7. How might decreased LH levels influence testosterone levels? What are potential causes of increased testosterone levels in women? What changes might occur in such women?
V. Endocrine Part 4
1. What is the test of choice to measure PTH levels? What other test do you need to properly interpret PTH results? What regulatory changes in serum chemistry tests would trigger PTH secretion?
2. Be able to distinguish among 1o & secondary hyperparathyroidism, hypoparathyroidism & pseudohypoparathyroidism. See the chart and summary.
3. What is the active form of Vitamin D? How might liver, kidney, and granulomatous diseases affect Vitamin D3 levels? What happens to Vitamin D levels in the winter (at least in the northern hemisphere)?
4. How do PTH levels and active Vitamin D interrelate?
5. How would renal failure, hypoparathyroidism, hyperparathyroidism, hypocalcemia & excessive Vit. D intake influence phosphate levels? [Be aware of the factors that interfere with phosphate determinations.]
6. When would a serum gastrin level be ordered? What factors might interfere?
7. What factors stimulate HGH release? What would you expect the HGH & IGF-1 levels to be in acromegaly, gigantism, and dwarfism? What is the connection between HGH & IGF-1?
8. Why might you want to order an IGF-1 test instead of HGH? How would severe liver disease & diabetes affect IGF-1 levels?
9. What conditions cause increases & decreases in pregnenolone levels?
10. What is the effect of aging on DHEA levels? How do acute & chronic stress affect DHEA levels?
MAMIE'S ANSWERS FROM HERE DOWN
WINTER 2009 FINAL EXAM STUDY GUIDE
I. Thyroid
1. Be familiar with specific thyroid hormone synthesis: feedback/role of TRH, TSH, tyrosine, iodine, percentage of T4 & T3 released by the gland. Tyrosine incorp iodine→monoiodotyrosine (MIT), adds 2nd iodine atom→diiodotyrosine (DIT), 2 DIT + thyroglobulin= T4, DIT + MIT + thyroglublin= T3. Hypothal secretes TRH→regulates prod of TSH, AKA thyrotropin, secreted by pituitary→TSH stimulates thyroid to produce T3 (7%) & T4 (93%)→negative feedback to hypothal causing dec TRH, pituitary causing dec TSH, therefore, dec prod of T3 & T4 by thyroid; TSH is major modulator of thyroid gland activity.
2. Know what proteins function as thyroid hormones carriers? TBG (thyroxine binding globulin) has highest binding affinity, carries 70% of hormones; TBPA (thyroid binding pre-albumin) has lower affinity, carries 20% of T4, NO T3; albumin has low affinity, binds 10% of T4 & 30% of T3. Bound proteins serve as a reservoir to replace free hormone fractions that have been utilized.
3. How might changes in TBG affect Total T4 & T3 levels? Inc in TBG→inc T4, dec T3RU & dec TBG→dec T4, inc T3RU. What can alter TBG levels? Pregnancy & pts on oral contraceptives→increases in TBG; protein loss, androgen excess→dec TBG. Falsely elevated T4 levels (TBG is inc so Total T4 levels appear inc, but FREE T4 is N).
4. Why is total T4 NOT the best test to evaluate thyroid function? See #3
5. Know the normal percentages of Free T4 & free T3 and their biologic activity? Free T3 & T4 are biologically active hormones, able to cross cell membranes into target tissues; most are bound to proteins. .02-.03% of T4 is unbound, or free (N is .7-2 ng/dL); .3% of T3 is unbound (N is 260-480 pg/dL).
6. Know how variations in TBG levels influence T3RU [See the TBG bus diagram. Be sure you understand what the T3RU uptake test actually measures!] T3RU is an indirect measure of T4, TBG & TBPA, and amount of unsat TBG & TBPA binding sites; see #3 for TBG influence on T3RU levels or bus diagram.
7. What does the FTI test measure? Calculated estimate of TOTAL T4 (FTI=T4xT3RU/100); corrects for changes in thyroid binding proteins that affect T4 level; helpful to dx hyper & hypothyroidism
8. Recognize hypErthyroidism vs hypOthyroidism (1o, 2o (pituitary) & 3o (hypothalamus)) from data provided. When would you want to use the TRH stimulation test? Read slides 16-20, 25; slides 8-9
9. Know how to use the FT4 or FTI to sort out TSH abnormalities. Low levels of T3 & T4 (mainly) stimulate secretion of TRH which results in TSH increase. Dec T4 w/ elevated TSH= thyroid prob; dec T4 w/ dec TSH=pituitary of hypothalamic prob. FTI is calculated estimate of TOTAL T4 & is increased in primary hyperthyroid & decreased in hypothyroid states, pituitary insufficiency & hypothalamic failure (FTI will match T4 levels)
10. What test would confirm a diagnosis of T3 toxicosis? Total T3/ T3 by RIA; T3 toxicosis is a rare form of hyperthyroidism w/ N T4 & elevated T3
11. Why might patients with “Euthyroid Sick Syndrome” have hypothyroidism symptoms & what test would confirm your suspicion? Hypothyroidism secondary to decreased peripheral conversion of T4→T3, decreased clearance of rT3, & decreased binding of thryroid hormones to TBG; see slide 26; thyroid function test (T4, free T4, T3, free T3, TSH)
12. When would you want to order a radioactive iodine uptake test (T3RU), or a thyroglobulin level (T3/T4)? Suspected hyper or hypothyroidism. What other test do you need to order simultaneously? TSH to differentiate between primary, secondary & tertiary hypo; single best test to screen for abN function of thyroid gland, see #9
13. What TSH & FT4 levels and antibodies are typically present in Graves Disease & Hashimoto’s thyroiditis? Graves: thyroid stimulating immunoglobulin (TSI) autoantibodies are directed against TSH receptor→over stimulate activity of thyroid (dt defect in T-suppressor cells); antiperoxidase & antithyroglobulin antibodies often seen; see high T3RU & T4, low TSH. Hashimoto’s: anti-TPO (anti-thyroid peroxidase, thyroperoxidase) & antithyroglobulin Abs; antibody titers much higher than in Graves; low T4 & T3RU, elevated TSH
II. Liver and Hepatitis
1. Know why the enzymes on a hepatic panel are not necessarily good indicators of liver function and what tests are better indicators of liver function? Enzymes are generally more indicative of liver damage than hepatocyte function; bilirubin, total protein, albumin, protime, BUN, & ammonia levels provide better indication of hepatic function.
2. What disease process is suggested when an increased ALP is greater than the increase in AST or ALT, and vice versa? ALP levels increased in both extrahepatic & intrahepatic obstructive biliary dz; AST & ALT increases in acute hep (20-100x) or cholestatic liver dz (10x). How would you verify that an increased in ALP originated in the liver? Order isoenzymes: ALP-1 liver, ALP-2 bone, intestine, placenta, certain cancers.
3. Know the various interpretations of the AST/ALT ratio. Usu greater than 1 w/ alcoholic cirrhosis, congestion, metastatic tumor; greater than 2-3 if alcoholic hep; less than 1 w/ acute hep, chronic viral hep & infectious mono (ratio inaccurate if AST > 10x normal)
4. Know how the prothrombin time (PT) as a prognostic tool in chronic liver dz. PT is sensitive to levels of clotting factors (esp changes in VII); PT<2xN: good prognosis for recovery, PT>2xN: poor prognosis; N to mild elevation: chronic liver dz, marked elevation: acute fulminant necrosis, chronic active hepatitis, end-stage liver dz
5. Know whether the cause of jaundice is pre-hepatic, hepatic, or post-hepatic based on the patterns of conjugated & unconjugated bilirubin in serum and urine. Hyperbilirubinemia can result from inc in indirect, direct or both; indirect inc dt RBC hemolysis, ineffective erythropoiesis, hepatitis, cirrhosis, or drugs (hepatic, pre-hepatic); direct inc dt gallstones, extrahepatic duct obstruction, metastatic CA, or other intrahepatic cholestasis (hepatic, post-hepatic)
6. What tests are included on a typical “acute hepatitis panel?” Anti_HAV, HBsAg, Anti-HBc, Anti-HCV. Why doesn’t the panel include testing for HDV (not appropriate in those w/ no underlying HBV infxn), HEV, HGV (cause <1% of acute hep in U.S. so not routinely part of panel)?
7. What degree of elevation in AST & ALT typically occurs in acute hep? 20-100x Why might unconjugated & conjugated bilirubin increase in acute hepatitis? Hepatocytes are damaged→dec ability to extract unconj bili from blood→inc unconj bili; leakage from damaged hepatocytes or blockage of small bile ducts→inc conj bili
8. What test would confirm acute Hep A? Presence of Anti-HAV IgM w/ IgG neg (NO antigen test available!!). Acute Hep B? Presence of Anti-HBc IgM (+ HBsAg could indicate either acute HBV or chronic HBV; if HBeAg also present w/ Anti-HAV IgM, indicates highly infectious state). What tests are used to confirm Acute Hep C? HCV RNA PCR looks for evidence of viral replication; qualitative HCV RNA test is recommended for those w/ + Anti-HCV (Elisa) to look for active infxn. What must you do if the confirmatory tests are positive? Must report. Quantitative HCV RNA is used to determine viral load & to monitor antiviral therapy
9. What’s the clinical significance of a positive HBsAg test? Can indicate either acute HBV or chronic HBV. How do you distinguish between acute & chronic Hep B in a person with a “+” HBsAg test? Do Anti-HBc (if IgM, acute; if IgG chronic; HBe Ag=highly infectious, Antibody to HBe suggests good prognosis for resolution of acute infxn)
10. Know the order of appearance of the various antigens & antibodies in a person who recovers from Hepatitis B. slides 24-32
11. Know the pattern for a person who develops chronic Hepatitis B and how to distinguish the replicative from the non-replicative states. Slides 24-32 & #9. Be familiar with HBV testing summary slide. Slide 35. How is chronic Hep B defined? Anti-HBc Ab IgG; persistence of HBe Ag >20 weeks suggests chronic HBV; persistence of HBsAg for more than 6 mos defines chronic HBV infxn
12. What is the “core window?” AKA serologic gap, the period between disappearance of HBs Ag & appearance of Anti-HBs Ab (usu 2-6 weeks). What tests will be positive during that period? Anti-HBc IgM will be positive during that window, also total anti-HBc & either HBe Ag or anti-HBe
13. When might you want to screen for Hep C Virus? In persons who: have ever injected illegal drugs, received blood transfusions prior to ’92, ever been on long-term dialysis, received blood from donor who later tested + for HCV, have persistently abN ALT values. What is the significance of a positive Hepatitis C Virus ELISA test (current or resolved) and a negative RIBA test? “If the immunoblot test for anti-HCV is positive, the patient has most likely recovered from hepatitis C and has persistent antibody without virus.” (http://www.hepcnet.net/serologic_tests.html) So…if the ELISA test is positive for Hep C virus & the RIBA test is negative, then the patient has a current infection OR the ELISA test is false positive.
14. What’s the significance of a positive Hep C Virus ELISA test & a negative qualitative HCV RNA test? Resolved infxn
15. What test would monitor the effectiveness of anti-viral therapy in a confirmed chronic Hep C patient? Quantitative HCV RNA; also checks viral load BUT viral load doesn’t correlate w/ severity & prognosis, so… Why is it advisable to do HCV genotyping in this patient? Type 1b has a higher risk of hepatocellular CA
16. When might you order the Hep D virus? When the person already has Hep B & there was potential exposure to Hep D OR when someone has potentially been exposed to both Hep B & D at the same time. Understand the difference between co-infection & super-infection for HBV & HDV and their respective test patterns. Coinfection: simultaneous infxn of acute HBV & acute HDV; presence of HBsAg & anti-HBc IgM, which indicates acute HBV AND anti-HDV IgM documents acute HDV. Superinfection: acute HDV infxn in chronic HBV carrier (more common); presence of HBs Ag & anti-HDV IgM, absence of anti-HBc IgM
17. When might you decide to test for the Hepatitis E virus? (postabsorptive) testing indicated in hepatitis acquired after travel to Mexico, India, Africa, Burma & Russia; serologic markers for Heps A, B, C, EBV & CMV are absent; pregnant women in 3rd trimester suffer inc rates of mortality; fecal-oral route
III. Endocrine: Parts 1 and 2
1. How would you optimally instruct your patient to prepare for an OGTT? The patient is instructed NOT to restrict carbohydrate intake in the days or weeks before the test (150-300 g CHO/day for 3 days prior). The test should not be done during an illness (even a cold).
2. What happens to blood GLU and K if you don’t separate RBCs from serum promptly? Glucose levels will drop ~10mg/dl per hour at room temp in a whole blood sample dt RBC utilization of glucose (so it’s best to remove serum ASAP after clotting); when RBCs sit in serum, leakage of K+ from RBCs can cause a spurious inc. in K+ levels in the serum
3. Know criteria for diagnosing diabetes: Adult FBS: >126 on 2 tests = diabetes, >100 = impaired fasting glucose (need 2 test >100 to dx pre-diabetes); 2-Hr postprandial: ≥200 on 2 tests= diabetic, 140-199 on 2 tests = impaired glucose tolerance (AND pre-diabetes) & follow up with GTT; 2HrPPG=2HrGTT; GTT will test FBS, 30 min, 1hr, 2hr, 3hr…
4. Be familiar with the endocrine interpretation of OGTT. FBS to 1hr: reflects pancreatic fxn & insulin (how well insulin can control glucose increase); 1-2hr: liver response to convert glu→glycogen for storage; 2-4hr: pancreatic response to decreased glu by secreting glucagon (results in glycogenolysis & gluconeogenesis in liver); 4-5hr: adrenal response (cortisol increases glycogen breakdown & gluconeogenesis, ie stress can inc blood glu); 5-6hr: anterior pituitary response to ACTH stimulation of adrenals. How would adrenal fatigue affect the outcome of a 5-hour OGTT? Low cortisol levels in adrenal fatigue→decreased glucose levels
5. What are the current criteria to dx reactive (post-prandial) hypoglycemia? Dx is made by demonstrating a low plasma glucose of <50mg/dL during a symptomatic episode
6. What are the indications for performing an insulin assay? Evaluation of patients with fasting hypoglycemia, evaluation of abN CHO & lipid metabolism, diagnosis of insulinemia→tumor of pancreatic islet beta cells (& APUD stem cells): hyperinsulinemia (>30mU/ml) despite hypoglycemia
7. When combining OGTT & insulin tests, what patterns would you find with IDDM (low fasting insulin, flat insulin curves on OGTT), IGT (N fasting insulin, delayed rise in curve on OGTT), & NIDDM (persistently high insulin levels & hyperglycemia)? Why might Cushing’s Synd. predispose one to high insulin levels? Cushing’s Synd is cortisol excess→hyperglycemia→insulin resistance→high insulin levels dt decrease in insulin sensitivity
8. What level of HgbA1c is considered evidence of good diabetic control? 7%. How often should the test be repeated? Glycosylated hemoglobin values reflect average blood sugar for the 2- to 3-month period before the test. Use to determine hyperglycemia duration in new pt: GHb elevation occurs ab 3 weeks after sustained elevation in blood glu & takes at least 4 weeks to decrease after sustained reduction in blood glu. Use to evaluate diabetic treatment every 3 mos. Is A1c useful for brittle diabetics? Yes, “evaluation of ‘brittle diabetics’ whose glucose changes significantly day to day” is indicated.
9. Know cortisol & ACTH patterns for Cushing’s Syndrome (high cortisol, low ACTH) vs. Cushing’s Dz (high cortisol & ACTH) & Addison’s Dz (low cortisol, high ACTH). What test is useful to screen for Cushing’s Syndrome? 24 hr urinary free cortisol (also useful for Addison’s dz)
10. How might Cushing’s Syndrome & Addison’s Dz influence test results on a Basic Metabolic Profile?
Cl- Glu K+ Na+ Ca++
Cushing’s > > < > <
Addison’s < < > < >
Be able to predict the effect of excess cortisol on thyroid gland function. From http://www.virginiahopkinstestkits.com/cortisolzava.html: “Too much cortisol, again caused by the adrenal glands’ response to excessive stressors, causes the tissues to no longer respond to the thyroid hormone signal. It creates a condition of thyroid resistance, meaning that thyroid hormone levels can be normal, but tissues fail to respond as efficiently to the thyroid signal. This resistance to the thyroid hormone signal caused by high cortisol is not just restricted to thyroid hormone but applies to all other hormones such as insulin, progesterone, estrogens, testosterone, and even cortisol itself. When cortisol gets too high, you start getting resistance from the hormone receptors, and it requires more hormones to create the same effect. That’s why chronic stress, which elevates cortisol levels, makes you feel so rotten—none of the hormones are allowed to work at optimal levels.”
So excess cortisol→decreased thyroid gland function dt thyroid hormone resistance
Low cortisol levels→decreased thyroid function
11. What is the Dexamethasone Suppression test used to dx? Important in dx of adrenal hyperfunction—Cushing’s, helps distinguish cause of hyperfunction (pituitary-dependent Cushing’s or ectopic ACTH); increased plasma cortisol suppresses ACTH secretion, decreased stimulates. Read more slides 47-49
IV. Endocrine Part 3
1. What is the test of choice to measure PTH levels? Intact PTH. What other test do you need to properly interpret PTH results? Serum calcium level. What regulatory changes in serum chemistry tests would trigger PTH secretion? dec Ca++→inc PTH secretion; PTH release causes inc renal tubular Ca++ reabsorption, dec tubular reabsorption of phosphorus, inc osteoclastic activity→bone Ca++, inc production of active Vit D in kidney.
2. Be able to distinguish among 1o (parathyroid gland abnormaity adenoma—inc PTH) & secondary (too much PTH prod by parathyroid glands in response to low blood Ca++ that is dt another condition; renal dz/chronic renal failure; Vit D deficiency) hyperparathyroidism, hypoparathyroidism (decreased PTH—Graves dz) & pseudohypoparathyroidism (hypercalcemia of malignancy—PTH ineffective in peripheral tissues dt lack of receptor sensitivity; PRIMARY DEFECT in renal tubular responsiveness to PTH). See the chart and summary.
3. What is the active form of Vitamin D? 1,25-di-hydroxy-cholecalciferol (calcitriol). How might liver (dec), kidney (dec), and granulomatous (inc) diseases affect Vitamin D3 levels? What happens to Vitamin D levels in the winter (at least in the northern hemisphere)? Dec levels dt lack of sunlight or use of sunscreens
4. How do PTH levels and active Vitamin D interrelate? 1-hydroxylation rxn (25-hydroxy-cholecalciferol→1,25-di-hydroxyl-cholecalciferol) is stimulated by PTH & by dec Ca++ & phosphate; inhibited by high Ca++ & phosphate; dec active vit D3 in hypoparathyroidism, inc active vit D3 in primary hyperparathyroidism
5. How would renal failure (inc), hypoparathyroidism (inc), hyperparathyroidism (dec), hypocalcemia (inc) & excessive Vit. D intake inc) influence phosphate levels? [Be aware of the factors that interfere with phosphate determinations.] interfering factors: laxatives or enemas containing phosphate→inc; drugs; seasonal variation (highest in May & June, lowest in winter)
6. When would a serum gastrin level be ordered? To dx gastrinoma & Zollinger-Ellison syndrome; best to draw a fasting sample b/c levels fluctuate in relation to meals. What factors might interfere? Non-fasting state, elderly, insulin-dependent diabetics, those taking histamine blockers, purple pills (prilosec), steroids (falsely inc values)
7. What factors stimulate HGH release? Produced by anterior pituitary in response to hypothalamic Growth Hormone Releasing Hormone (GHRH), deep sleep, exercise, fasting, hypoglycemia, glucagon, excess insulin, stress, vasopressin. What would you expect the HGH & IGF-1 levels to be in acromegaly (HGH: inc, IGF-1: inc), gigantism (HGH: inc, IGF-1: inc), and dwarfism (HGH: inc in Laron’s dwarfism—dt HGH resistance in tissues, dec in pituitary dwarfism, IGF-1: dec in pituitary & Laron dwarfism)? What is the connection between HGH & IGF-1? IGF-1 (AKA Somatomedin C) is produced by liver in response to HGH secretion; it mediates HGH activity & glu metabolism; not subject to as much variation as HGH (longer ½ life); expect to see large inc in IGF-1 during puberty
8. Why might you want to order an IGF-1 test instead of HGH? Not subject to as much variation. How would severe liver disease & diabetes affect IGF-1 levels? Hyperglycemia & severe liver dz dec IGF-1 levels (hypoglycemia inc levels).
9. What conditions cause increases & decreases in pregnenolone levels? Inc: some forms of idiopathic hirsutism & Congenital Adrenal Hyperplasia (CAH), specifically those in which there is a deficit of either 17 α-hydroxylase or 3 β-hydroxysteroid dehydrogenase; 90-95% of CAH cases are dt dec 21-hydroxylase; also if metabolic pathway is blocked (precursor compounds inc) Dec: seen in adrenocortical failure
10. What is the effect of aging on DHEA levels? Lower in childhood, spike before onset of puberty (adrenarche), the dec significanty with age (dec begins around age 30, with >80% dec by 75 yo) How does acute & chronic stress affect DHEA levels? Acute stress inc levels, chronic stress dec levels (dt “pregnenolone steal”)
I. Thyroid
1. Be familiar with specific thyroid hormone synthesis: feedback/role of TRH, TSH, tyrosine, iodine, percentage of T4 & T3 released by the gland.
2. Know what proteins function as thyroid hormones carriers?
3. How might changes in TBG affect Total T4 & T3 levels? What can alter TBG levels?
4. Why is total T4 NOT the best test to evaluate thyroid function?
5. Know the normal percentages of Free T4 & free T3 and their biologic activity?
6. Know how variations in TBG levels influence T3RU [See the TBG bus diagram. Be sure you understand what the T3RU uptake test actually measures!]
7. What does the FTI test measure?
8. Recognize hypErthyroidism vs hypOthyroidism (1o, 2o & 3o) from data provided. When would you want to use the TRH stimulation test?
9. Know how to use the FT4 or FTI to sort out TSH abnormalities.
10. What test would confirm a diagnosis of T3 toxicosis?
11. Why might patients with “Euthyroid Sick Syndrome” have hypothyroidism symptoms & what test would confirm your suspicion?
12. When would you want to order a radioactive iodine uptake test, or a thyroglobulin level? What other test do you need to order simultaneously?
13. What TSH & FT4 levels and antibodies are typically present in Graves Disease & Hashimoto’s thyroiditis?
II. Liver and Hepatitis
1. Know why the enzymes on a hepatic panel are not necessarily good indicators of liver function and what tests are better indicators of liver function?
2. What disease process is suggested when an increased ALP is greater than the increase in AST or ALT, and vice versa? How would you verify that an increased in ALP originated in the liver?
3. Know the various interpretations of the AST/ALT ratio.
4. Know how the prothrombin time (PT) as a prognostic tool in chronic liver dz.
5. Know whether the cause of jaundice is pre-hepatic, hepatic, or post-hepatic based on the patterns of conjugated & unconjugated bilirubin in serum and urine.
6. What tests are included on a typical “acute hepatitis panel?” Why doesn’t the panel include testing for HDV, HEV, or HGV?
7. What degree of elevation in AST & ALT typically occurs in acute hep? Why might unconjugated & conjugated bilirubin increase in acute hepatitis?
8. What test would confirm acute Hep A? Acute Hep B? What tests are used to confirm Acute Hep C? What must you do if the confirmatory tests are positive?
9. What’s the clinical significance of a positive HBsAg test? How do you distinguish between acute & chronic Hep B in a person with a “+” HBsAg test?
10. Know the order of appearance of the various antigens & antibodies in a person who recovers from Hepatitis B.
11. Know the pattern for a person who develops chronic Hepatitis B and how to distinguish the replicative from the non-replicative states. Be familiar with HBV testing summary slide. How is chronic Hep B defined?
12. What is the “core window?” What tests will be positive during that period?
13. When might you want to screen for Hep C Virus? What is the significance of a positive Hepatitis C Virus ELISA test and a negative RIBA test?
14. What’s the significance of a positive Hep C Virus ELISA test & a negative qualitative HCV RNA test?
15. What test would monitor the effectiveness of anti-viral therapy in a confirmed chronic Hep C patient? Why is it advisable to do HCV genotyping in this patient?
16. When might you order the Hep D virus? Understand the difference between co-infection & super-infection for HBV & HDV and their respective test patterns.
17. When might you decide to test for the Hepatitis E virus? (postabsorptive)
III. Endocrine: Parts 1 and 2
1. How would you optimally instruct your patient to prepare for an OGTT?
2. What happens to blood GLUC and K if you don’t separate RBCs from serum promptly?
3. Know: Adult FBS, 2-Hr postprandial & 2-Hr GTT criteria for diagnosing diabetes, impaired fasting glucose & impaired glucose tolerance.
4. Be familiar with the endocrine interpretation of OGTT. How would adrenal fatigue affect the outcome of a 5-hour OGTT?
5. What are the current criteria to dx reactive (post-prandial) hypoglycemia?
6. What are the indications for performing an insulin assay?
7. When combining OGGT & insulin tests, what patterns would you find with IDDM, IGT, & NIDDM? Why might Cushing’s Synd. predispose one to high insulin levels?\
8. What level of HgbA1c is considered evidence of good diabetic control? How often should the test be repeated? Is A1c useful for brittle diabetics?
9. Know cortisol & ACTH patterns for Cushing’s Syndrome vs. Dz, & Addison’s Dz. What test is useful to screen for Cushing’s Syndrome?
10. How might Cushing’s Syndrome & Addison’s Dz influence test results on a Basic Metabolic Profile? Be able to predict the effect of excess cortisol on thyroid gland function.
11. What is the Dexamethasone Suppression test used to dx?
IV. Endocrine Part 3: Menstrual Cycles
1. What is the significance of low estrogen levels during the follicular phase of the cycle?
2. What is the significance of elevated estradiol levels in males?
3. How do estrogen levels influence secretion of LH? How do the LH & FSH levels differ in primary & secondary hypogonadism? In infertility?
4. How do FSH & LH levels change after menopause? At what point of a “normal” menstrual cycle would FSH & LH levels be the highest?
5. What are the indications for testing progesterone? How do the levels change over the course of a “normal” menstrual cycle? What happens to progesterone production in anovulatory cycles?
6. What are the effects of increased Prolactin levels? What difference in prolactin levels might be seen between nursing & non-nursing mothers?
7. How might decreased LH levels influence testosterone levels? What are potential causes of increased testosterone levels in women? What changes might occur in such women?
V. Endocrine Part 4
1. What is the test of choice to measure PTH levels? What other test do you need to properly interpret PTH results? What regulatory changes in serum chemistry tests would trigger PTH secretion?
2. Be able to distinguish among 1o & secondary hyperparathyroidism, hypoparathyroidism & pseudohypoparathyroidism. See the chart and summary.
3. What is the active form of Vitamin D? How might liver, kidney, and granulomatous diseases affect Vitamin D3 levels? What happens to Vitamin D levels in the winter (at least in the northern hemisphere)?
4. How do PTH levels and active Vitamin D interrelate?
5. How would renal failure, hypoparathyroidism, hyperparathyroidism, hypocalcemia & excessive Vit. D intake influence phosphate levels? [Be aware of the factors that interfere with phosphate determinations.]
6. When would a serum gastrin level be ordered? What factors might interfere?
7. What factors stimulate HGH release? What would you expect the HGH & IGF-1 levels to be in acromegaly, gigantism, and dwarfism? What is the connection between HGH & IGF-1?
8. Why might you want to order an IGF-1 test instead of HGH? How would severe liver disease & diabetes affect IGF-1 levels?
9. What conditions cause increases & decreases in pregnenolone levels?
10. What is the effect of aging on DHEA levels? How do acute & chronic stress affect DHEA levels?
MAMIE'S ANSWERS FROM HERE DOWN
WINTER 2009 FINAL EXAM STUDY GUIDE
I. Thyroid
1. Be familiar with specific thyroid hormone synthesis: feedback/role of TRH, TSH, tyrosine, iodine, percentage of T4 & T3 released by the gland. Tyrosine incorp iodine→monoiodotyrosine (MIT), adds 2nd iodine atom→diiodotyrosine (DIT), 2 DIT + thyroglobulin= T4, DIT + MIT + thyroglublin= T3. Hypothal secretes TRH→regulates prod of TSH, AKA thyrotropin, secreted by pituitary→TSH stimulates thyroid to produce T3 (7%) & T4 (93%)→negative feedback to hypothal causing dec TRH, pituitary causing dec TSH, therefore, dec prod of T3 & T4 by thyroid; TSH is major modulator of thyroid gland activity.
2. Know what proteins function as thyroid hormones carriers? TBG (thyroxine binding globulin) has highest binding affinity, carries 70% of hormones; TBPA (thyroid binding pre-albumin) has lower affinity, carries 20% of T4, NO T3; albumin has low affinity, binds 10% of T4 & 30% of T3. Bound proteins serve as a reservoir to replace free hormone fractions that have been utilized.
3. How might changes in TBG affect Total T4 & T3 levels? Inc in TBG→inc T4, dec T3RU & dec TBG→dec T4, inc T3RU. What can alter TBG levels? Pregnancy & pts on oral contraceptives→increases in TBG; protein loss, androgen excess→dec TBG. Falsely elevated T4 levels (TBG is inc so Total T4 levels appear inc, but FREE T4 is N).
4. Why is total T4 NOT the best test to evaluate thyroid function? See #3
5. Know the normal percentages of Free T4 & free T3 and their biologic activity? Free T3 & T4 are biologically active hormones, able to cross cell membranes into target tissues; most are bound to proteins. .02-.03% of T4 is unbound, or free (N is .7-2 ng/dL); .3% of T3 is unbound (N is 260-480 pg/dL).
6. Know how variations in TBG levels influence T3RU [See the TBG bus diagram. Be sure you understand what the T3RU uptake test actually measures!] T3RU is an indirect measure of T4, TBG & TBPA, and amount of unsat TBG & TBPA binding sites; see #3 for TBG influence on T3RU levels or bus diagram.
7. What does the FTI test measure? Calculated estimate of TOTAL T4 (FTI=T4xT3RU/100); corrects for changes in thyroid binding proteins that affect T4 level; helpful to dx hyper & hypothyroidism
8. Recognize hypErthyroidism vs hypOthyroidism (1o, 2o (pituitary) & 3o (hypothalamus)) from data provided. When would you want to use the TRH stimulation test? Read slides 16-20, 25; slides 8-9
9. Know how to use the FT4 or FTI to sort out TSH abnormalities. Low levels of T3 & T4 (mainly) stimulate secretion of TRH which results in TSH increase. Dec T4 w/ elevated TSH= thyroid prob; dec T4 w/ dec TSH=pituitary of hypothalamic prob. FTI is calculated estimate of TOTAL T4 & is increased in primary hyperthyroid & decreased in hypothyroid states, pituitary insufficiency & hypothalamic failure (FTI will match T4 levels)
10. What test would confirm a diagnosis of T3 toxicosis? Total T3/ T3 by RIA; T3 toxicosis is a rare form of hyperthyroidism w/ N T4 & elevated T3
11. Why might patients with “Euthyroid Sick Syndrome” have hypothyroidism symptoms & what test would confirm your suspicion? Hypothyroidism secondary to decreased peripheral conversion of T4→T3, decreased clearance of rT3, & decreased binding of thryroid hormones to TBG; see slide 26; thyroid function test (T4, free T4, T3, free T3, TSH)
12. When would you want to order a radioactive iodine uptake test (T3RU), or a thyroglobulin level (T3/T4)? Suspected hyper or hypothyroidism. What other test do you need to order simultaneously? TSH to differentiate between primary, secondary & tertiary hypo; single best test to screen for abN function of thyroid gland, see #9
13. What TSH & FT4 levels and antibodies are typically present in Graves Disease & Hashimoto’s thyroiditis? Graves: thyroid stimulating immunoglobulin (TSI) autoantibodies are directed against TSH receptor→over stimulate activity of thyroid (dt defect in T-suppressor cells); antiperoxidase & antithyroglobulin antibodies often seen; see high T3RU & T4, low TSH. Hashimoto’s: anti-TPO (anti-thyroid peroxidase, thyroperoxidase) & antithyroglobulin Abs; antibody titers much higher than in Graves; low T4 & T3RU, elevated TSH
II. Liver and Hepatitis
1. Know why the enzymes on a hepatic panel are not necessarily good indicators of liver function and what tests are better indicators of liver function? Enzymes are generally more indicative of liver damage than hepatocyte function; bilirubin, total protein, albumin, protime, BUN, & ammonia levels provide better indication of hepatic function.
2. What disease process is suggested when an increased ALP is greater than the increase in AST or ALT, and vice versa? ALP levels increased in both extrahepatic & intrahepatic obstructive biliary dz; AST & ALT increases in acute hep (20-100x) or cholestatic liver dz (10x). How would you verify that an increased in ALP originated in the liver? Order isoenzymes: ALP-1 liver, ALP-2 bone, intestine, placenta, certain cancers.
3. Know the various interpretations of the AST/ALT ratio. Usu greater than 1 w/ alcoholic cirrhosis, congestion, metastatic tumor; greater than 2-3 if alcoholic hep; less than 1 w/ acute hep, chronic viral hep & infectious mono (ratio inaccurate if AST > 10x normal)
4. Know how the prothrombin time (PT) as a prognostic tool in chronic liver dz. PT is sensitive to levels of clotting factors (esp changes in VII); PT<2xN: good prognosis for recovery, PT>2xN: poor prognosis; N to mild elevation: chronic liver dz, marked elevation: acute fulminant necrosis, chronic active hepatitis, end-stage liver dz
5. Know whether the cause of jaundice is pre-hepatic, hepatic, or post-hepatic based on the patterns of conjugated & unconjugated bilirubin in serum and urine. Hyperbilirubinemia can result from inc in indirect, direct or both; indirect inc dt RBC hemolysis, ineffective erythropoiesis, hepatitis, cirrhosis, or drugs (hepatic, pre-hepatic); direct inc dt gallstones, extrahepatic duct obstruction, metastatic CA, or other intrahepatic cholestasis (hepatic, post-hepatic)
6. What tests are included on a typical “acute hepatitis panel?” Anti_HAV, HBsAg, Anti-HBc, Anti-HCV. Why doesn’t the panel include testing for HDV (not appropriate in those w/ no underlying HBV infxn), HEV, HGV (cause <1% of acute hep in U.S. so not routinely part of panel)?
7. What degree of elevation in AST & ALT typically occurs in acute hep? 20-100x Why might unconjugated & conjugated bilirubin increase in acute hepatitis? Hepatocytes are damaged→dec ability to extract unconj bili from blood→inc unconj bili; leakage from damaged hepatocytes or blockage of small bile ducts→inc conj bili
8. What test would confirm acute Hep A? Presence of Anti-HAV IgM w/ IgG neg (NO antigen test available!!). Acute Hep B? Presence of Anti-HBc IgM (+ HBsAg could indicate either acute HBV or chronic HBV; if HBeAg also present w/ Anti-HAV IgM, indicates highly infectious state). What tests are used to confirm Acute Hep C? HCV RNA PCR looks for evidence of viral replication; qualitative HCV RNA test is recommended for those w/ + Anti-HCV (Elisa) to look for active infxn. What must you do if the confirmatory tests are positive? Must report. Quantitative HCV RNA is used to determine viral load & to monitor antiviral therapy
9. What’s the clinical significance of a positive HBsAg test? Can indicate either acute HBV or chronic HBV. How do you distinguish between acute & chronic Hep B in a person with a “+” HBsAg test? Do Anti-HBc (if IgM, acute; if IgG chronic; HBe Ag=highly infectious, Antibody to HBe suggests good prognosis for resolution of acute infxn)
10. Know the order of appearance of the various antigens & antibodies in a person who recovers from Hepatitis B. slides 24-32
11. Know the pattern for a person who develops chronic Hepatitis B and how to distinguish the replicative from the non-replicative states. Slides 24-32 & #9. Be familiar with HBV testing summary slide. Slide 35. How is chronic Hep B defined? Anti-HBc Ab IgG; persistence of HBe Ag >20 weeks suggests chronic HBV; persistence of HBsAg for more than 6 mos defines chronic HBV infxn
12. What is the “core window?” AKA serologic gap, the period between disappearance of HBs Ag & appearance of Anti-HBs Ab (usu 2-6 weeks). What tests will be positive during that period? Anti-HBc IgM will be positive during that window, also total anti-HBc & either HBe Ag or anti-HBe
13. When might you want to screen for Hep C Virus? In persons who: have ever injected illegal drugs, received blood transfusions prior to ’92, ever been on long-term dialysis, received blood from donor who later tested + for HCV, have persistently abN ALT values. What is the significance of a positive Hepatitis C Virus ELISA test (current or resolved) and a negative RIBA test? “If the immunoblot test for anti-HCV is positive, the patient has most likely recovered from hepatitis C and has persistent antibody without virus.” (http://www.hepcnet.net/serologic_tests.html) So…if the ELISA test is positive for Hep C virus & the RIBA test is negative, then the patient has a current infection OR the ELISA test is false positive.
14. What’s the significance of a positive Hep C Virus ELISA test & a negative qualitative HCV RNA test? Resolved infxn
15. What test would monitor the effectiveness of anti-viral therapy in a confirmed chronic Hep C patient? Quantitative HCV RNA; also checks viral load BUT viral load doesn’t correlate w/ severity & prognosis, so… Why is it advisable to do HCV genotyping in this patient? Type 1b has a higher risk of hepatocellular CA
16. When might you order the Hep D virus? When the person already has Hep B & there was potential exposure to Hep D OR when someone has potentially been exposed to both Hep B & D at the same time. Understand the difference between co-infection & super-infection for HBV & HDV and their respective test patterns. Coinfection: simultaneous infxn of acute HBV & acute HDV; presence of HBsAg & anti-HBc IgM, which indicates acute HBV AND anti-HDV IgM documents acute HDV. Superinfection: acute HDV infxn in chronic HBV carrier (more common); presence of HBs Ag & anti-HDV IgM, absence of anti-HBc IgM
17. When might you decide to test for the Hepatitis E virus? (postabsorptive) testing indicated in hepatitis acquired after travel to Mexico, India, Africa, Burma & Russia; serologic markers for Heps A, B, C, EBV & CMV are absent; pregnant women in 3rd trimester suffer inc rates of mortality; fecal-oral route
III. Endocrine: Parts 1 and 2
1. How would you optimally instruct your patient to prepare for an OGTT? The patient is instructed NOT to restrict carbohydrate intake in the days or weeks before the test (150-300 g CHO/day for 3 days prior). The test should not be done during an illness (even a cold).
2. What happens to blood GLU and K if you don’t separate RBCs from serum promptly? Glucose levels will drop ~10mg/dl per hour at room temp in a whole blood sample dt RBC utilization of glucose (so it’s best to remove serum ASAP after clotting); when RBCs sit in serum, leakage of K+ from RBCs can cause a spurious inc. in K+ levels in the serum
3. Know criteria for diagnosing diabetes: Adult FBS: >126 on 2 tests = diabetes, >100 = impaired fasting glucose (need 2 test >100 to dx pre-diabetes); 2-Hr postprandial: ≥200 on 2 tests= diabetic, 140-199 on 2 tests = impaired glucose tolerance (AND pre-diabetes) & follow up with GTT; 2HrPPG=2HrGTT; GTT will test FBS, 30 min, 1hr, 2hr, 3hr…
4. Be familiar with the endocrine interpretation of OGTT. FBS to 1hr: reflects pancreatic fxn & insulin (how well insulin can control glucose increase); 1-2hr: liver response to convert glu→glycogen for storage; 2-4hr: pancreatic response to decreased glu by secreting glucagon (results in glycogenolysis & gluconeogenesis in liver); 4-5hr: adrenal response (cortisol increases glycogen breakdown & gluconeogenesis, ie stress can inc blood glu); 5-6hr: anterior pituitary response to ACTH stimulation of adrenals. How would adrenal fatigue affect the outcome of a 5-hour OGTT? Low cortisol levels in adrenal fatigue→decreased glucose levels
5. What are the current criteria to dx reactive (post-prandial) hypoglycemia? Dx is made by demonstrating a low plasma glucose of <50mg/dL during a symptomatic episode
6. What are the indications for performing an insulin assay? Evaluation of patients with fasting hypoglycemia, evaluation of abN CHO & lipid metabolism, diagnosis of insulinemia→tumor of pancreatic islet beta cells (& APUD stem cells): hyperinsulinemia (>30mU/ml) despite hypoglycemia
7. When combining OGTT & insulin tests, what patterns would you find with IDDM (low fasting insulin, flat insulin curves on OGTT), IGT (N fasting insulin, delayed rise in curve on OGTT), & NIDDM (persistently high insulin levels & hyperglycemia)? Why might Cushing’s Synd. predispose one to high insulin levels? Cushing’s Synd is cortisol excess→hyperglycemia→insulin resistance→high insulin levels dt decrease in insulin sensitivity
8. What level of HgbA1c is considered evidence of good diabetic control? 7%. How often should the test be repeated? Glycosylated hemoglobin values reflect average blood sugar for the 2- to 3-month period before the test. Use to determine hyperglycemia duration in new pt: GHb elevation occurs ab 3 weeks after sustained elevation in blood glu & takes at least 4 weeks to decrease after sustained reduction in blood glu. Use to evaluate diabetic treatment every 3 mos. Is A1c useful for brittle diabetics? Yes, “evaluation of ‘brittle diabetics’ whose glucose changes significantly day to day” is indicated.
9. Know cortisol & ACTH patterns for Cushing’s Syndrome (high cortisol, low ACTH) vs. Cushing’s Dz (high cortisol & ACTH) & Addison’s Dz (low cortisol, high ACTH). What test is useful to screen for Cushing’s Syndrome? 24 hr urinary free cortisol (also useful for Addison’s dz)
10. How might Cushing’s Syndrome & Addison’s Dz influence test results on a Basic Metabolic Profile?
Cl- Glu K+ Na+ Ca++
Cushing’s > > < > <
Addison’s < < > < >
Be able to predict the effect of excess cortisol on thyroid gland function. From http://www.virginiahopkinstestkits.com/cortisolzava.html: “Too much cortisol, again caused by the adrenal glands’ response to excessive stressors, causes the tissues to no longer respond to the thyroid hormone signal. It creates a condition of thyroid resistance, meaning that thyroid hormone levels can be normal, but tissues fail to respond as efficiently to the thyroid signal. This resistance to the thyroid hormone signal caused by high cortisol is not just restricted to thyroid hormone but applies to all other hormones such as insulin, progesterone, estrogens, testosterone, and even cortisol itself. When cortisol gets too high, you start getting resistance from the hormone receptors, and it requires more hormones to create the same effect. That’s why chronic stress, which elevates cortisol levels, makes you feel so rotten—none of the hormones are allowed to work at optimal levels.”
So excess cortisol→decreased thyroid gland function dt thyroid hormone resistance
Low cortisol levels→decreased thyroid function
11. What is the Dexamethasone Suppression test used to dx? Important in dx of adrenal hyperfunction—Cushing’s, helps distinguish cause of hyperfunction (pituitary-dependent Cushing’s or ectopic ACTH); increased plasma cortisol suppresses ACTH secretion, decreased stimulates. Read more slides 47-49
IV. Endocrine Part 3
1. What is the test of choice to measure PTH levels? Intact PTH. What other test do you need to properly interpret PTH results? Serum calcium level. What regulatory changes in serum chemistry tests would trigger PTH secretion? dec Ca++→inc PTH secretion; PTH release causes inc renal tubular Ca++ reabsorption, dec tubular reabsorption of phosphorus, inc osteoclastic activity→bone Ca++, inc production of active Vit D in kidney.
2. Be able to distinguish among 1o (parathyroid gland abnormaity adenoma—inc PTH) & secondary (too much PTH prod by parathyroid glands in response to low blood Ca++ that is dt another condition; renal dz/chronic renal failure; Vit D deficiency) hyperparathyroidism, hypoparathyroidism (decreased PTH—Graves dz) & pseudohypoparathyroidism (hypercalcemia of malignancy—PTH ineffective in peripheral tissues dt lack of receptor sensitivity; PRIMARY DEFECT in renal tubular responsiveness to PTH). See the chart and summary.
3. What is the active form of Vitamin D? 1,25-di-hydroxy-cholecalciferol (calcitriol). How might liver (dec), kidney (dec), and granulomatous (inc) diseases affect Vitamin D3 levels? What happens to Vitamin D levels in the winter (at least in the northern hemisphere)? Dec levels dt lack of sunlight or use of sunscreens
4. How do PTH levels and active Vitamin D interrelate? 1-hydroxylation rxn (25-hydroxy-cholecalciferol→1,25-di-hydroxyl-cholecalciferol) is stimulated by PTH & by dec Ca++ & phosphate; inhibited by high Ca++ & phosphate; dec active vit D3 in hypoparathyroidism, inc active vit D3 in primary hyperparathyroidism
5. How would renal failure (inc), hypoparathyroidism (inc), hyperparathyroidism (dec), hypocalcemia (inc) & excessive Vit. D intake inc) influence phosphate levels? [Be aware of the factors that interfere with phosphate determinations.] interfering factors: laxatives or enemas containing phosphate→inc; drugs; seasonal variation (highest in May & June, lowest in winter)
6. When would a serum gastrin level be ordered? To dx gastrinoma & Zollinger-Ellison syndrome; best to draw a fasting sample b/c levels fluctuate in relation to meals. What factors might interfere? Non-fasting state, elderly, insulin-dependent diabetics, those taking histamine blockers, purple pills (prilosec), steroids (falsely inc values)
7. What factors stimulate HGH release? Produced by anterior pituitary in response to hypothalamic Growth Hormone Releasing Hormone (GHRH), deep sleep, exercise, fasting, hypoglycemia, glucagon, excess insulin, stress, vasopressin. What would you expect the HGH & IGF-1 levels to be in acromegaly (HGH: inc, IGF-1: inc), gigantism (HGH: inc, IGF-1: inc), and dwarfism (HGH: inc in Laron’s dwarfism—dt HGH resistance in tissues, dec in pituitary dwarfism, IGF-1: dec in pituitary & Laron dwarfism)? What is the connection between HGH & IGF-1? IGF-1 (AKA Somatomedin C) is produced by liver in response to HGH secretion; it mediates HGH activity & glu metabolism; not subject to as much variation as HGH (longer ½ life); expect to see large inc in IGF-1 during puberty
8. Why might you want to order an IGF-1 test instead of HGH? Not subject to as much variation. How would severe liver disease & diabetes affect IGF-1 levels? Hyperglycemia & severe liver dz dec IGF-1 levels (hypoglycemia inc levels).
9. What conditions cause increases & decreases in pregnenolone levels? Inc: some forms of idiopathic hirsutism & Congenital Adrenal Hyperplasia (CAH), specifically those in which there is a deficit of either 17 α-hydroxylase or 3 β-hydroxysteroid dehydrogenase; 90-95% of CAH cases are dt dec 21-hydroxylase; also if metabolic pathway is blocked (precursor compounds inc) Dec: seen in adrenocortical failure
10. What is the effect of aging on DHEA levels? Lower in childhood, spike before onset of puberty (adrenarche), the dec significanty with age (dec begins around age 30, with >80% dec by 75 yo) How does acute & chronic stress affect DHEA levels? Acute stress inc levels, chronic stress dec levels (dt “pregnenolone steal”)
