Adrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfb

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1. ADRENAL FUNCTION TESTS Adrenal glands Two small organs located above the kidneys. Have two functionally distinct parts Outer cortex(with three zones) Inner medulla – Catecholamines

2. HORMONES Adrenal cortex zone Adrenocorticosteroid hormone Zona Glomerulosa Mineralocorticoids Zona Fasciculata Glucocorticoids Zona reticularis Androgens

3. Cyclopentanoperhydrophenanthrene nucleus as their basic structure All steroid hormones are derived from cholesterol (major source - circulation) Most reactions catalyzed by enzymes of Cyt P450 family. Liver is the major site for steroid catabolism

4. Glucocorticoids 21C steroids Secreted in response to ACTH (secreted by pituitory ), which is in turn controlled by CRH. Cortisol (also known as hydrocortisone ) is the predominant glucocorticoid Mainly involved in the regulation of carbohydrate, lipid and protein metabolism. Powerful anti-inflammatory hormone. Cortisol exerts negative feedback on CRH and ACTH secretion Diurnal variation – highest in early morning, lowest near midnight.

5. Mineralocorticoids 21 C steroid Aldosterone is the most potent naturally occurring mineralocorticoid. Have effects on water and electrolyte balance.(sodium conservation, potassium and H ion excretion ) Regulated by renin –angiotensin system

6. Sex steroid hormones Secreted by zona reticularis. Dehydroepiandrosterone, dehydroepiandrosterone sulfate(DHEA-S), Androstenedione- Peripheral conversion to testosterone. Estrogen production negligible in adrenal cortex. Regulation not well understood yet

7. ADRENAL HYPERFUNCTION ADRENAL HYPOFUNCTION Cushing’s syndrome: Primary defect in adrenal gland (Adrenal adenoma, adrenal carcinoma etc ) Addison’s disease(primary adrenal insufficiency) Cushing’s disease/ Hyperpituitarism: Excess ACTH from pituitary –pituitary adenoma Secondary adrenal insufficiency: hypothalamic /pituitary disorder - impaired secretion of CRH/ACTH Androgen-secreting tumors of Ovaries, Testes, Ectopic ACTH by other tumors Administration of ACTH Primary hyperaldosteronism/Conn’s syndrome Adrenogenital syndrome/congenital adrenal hyperplasia

8. Adrenal function tests Help in diagnosis and monitoring of adrenal hypo/hyperfunction disorders. DHEA may be measured to determine cause of hirsuitism , amenorrhoea , infertility or precocious puberty in females.

9. Adrenal function tests Plasma Cortisol level Plasma ACTH level ACTH stimulation test/ CoSyntropin test Corticotropin-releasing hormone(CRH) stimulation test Dexamethasone Suppression Test 17-Hydrocortisol level Urinary free Cortisol Estimation of aldosterone in blood

10. Adrenal function tests contd … Urinary excretion of steroids Serum electrolytes Estimation of plasma renin activity Insulin induced hypoglycemic stimulation test. 17 alpha- Hydroxyprogesterone levels DHEA estimation

11. Plasma Cortisol level Diurnal rhythm Secretion maximum in morning Minimum at midnight Normal range 5-25 microgm /dl in morning(8 am) 2-5 microgm /dl in night(10 pm) Determined by immunoassay (ELISA/CLIA/RIA) Loss of diurnal rhythm may be an early indication of lesion at any point in hypothalamic –pituitary- adrenal axis

12. Plasma ACTH ACTH CORTISOL PROBABLE DISORDER Low High Primary hyperadrenalism Low Low Secondary adrenal insufficiency High Low Primary adrenocortical insufficiency High High Pituitory adenoma ( Cushings disease) or ectopic ACTH secretion.

13. Synacthen test/ACTH stimulation tests Used to assess adrenal reserve capacity Used to demonstrate the failure of adrenal gland to produce cortisol in response to ACTH Stimulation of adrenal cortex by synthetic ACTH( eg:synacthen /cosyntropin)injected iv/ im .

14. Normal response shows a rise in serum cortisol > 18microg/dl within 60mts of i.v administration of synacthen A person with primary adrenal failure doesnot respond.( rise <18microg/dl) Confirms the diagnosis of Addison’s disease

15. CRH Stimulation tests Definitive to differentiate pituitary causes from other causes Rise in ACTH secretion and cortisol levels following injection If there is no ACTH response after CRH stimulation tests, the disease is of pituitary origin

16. Dexamethasone Suppression Tests Used in diagnosis of Cushing’s syndrome. Low dose Dexamethasone Suppression Tests Dexamethasone is a potent suppressor of pituitary ACTH secretion and thereby cortisol level,causing 50% fall in serum cortisol with a dose as low as 1mg Patient takes dexamethasone tab at night and plasma cortisol is determined at 8 am the following morning Morning cortisol <5microgm/dl rules out adrenal tumors.

17. High dose dexamethasone suppression test Done to confirm Cushings disease Administer 2mg dexamethasone every 6 hrs for 2 days & cortisol measured next day morning. This dose suppresses plasma cortisol in Cushings disease.(drop atleast 50%) If plasma cortisol level is not suppressed, adrenal tumors producing high levels of cortisol or ectopic ACTH producing tumors are usually the aetiology

18. Urinary excretion of steroids Urinary steroids are 17 ketosteroids and 17 hydroxy steroids 17 ketosteroids are derived from both adrenal steroids and androgen from gonads, major contribution by cortisol and cortisone 17 hydroxy steroids are derived mainly from adrenal steroids Diagnostic value to assess functional status of adrenal cortex, particularly in females

19. Estimation of aldesterone in blood Increased levels are seen in primary hyperaldosteronism /Conn’s syndrome and bilateral adrenal hyperplasia Decreased aldosterone levels are seen in Addison’s disease

20. Estimation of plasma renin activity Helps to differentiate between primary and secondary hyperaldosteronism Enzyme activity is high in secondary, low in primary hyperaldosteronism

21. Urinary free Cortisol In plasma 70% cortisol is bound to cortisol binding globulin/ transcortin 20% cortisol is bound to albumin Rest is free,which is the biologically active form A definite fraction of unbound/free cortisol is exreted in urine unchanged 24 hr urine sample is collected Estimation of urinary free cortisol is a sensitive index of adrenal activity: Hyper/Hypofunction.

22. Lab findings in Adrenal hyperfunction Cause Plasma cortisol Urinary cortisol Plasma ACTH Dexamethasone suppression Adrenal adenoma Increased Increased decreased No suppression Adrenal carcinoma Increased Increased decreased No suppression Pituitory adenoma Increased Increased Increased Suppression with high dose Ectopic ACTH Increased Increased Increased No suppression

23. Lab findings in Adrenal hypofunction Cause for adrenal insufficiency Plasma cortisol Urinary cortisol Plasma ACTH ACTH stimulation CRH stimulation Primary low low High No effect No effect Secondary low low Low Normal/ exaggerated No effect

24. Lab findings in Conn’s syndrome Plasma Aldosterone levels are high Plasma renin activity is decreased due to feedback Serum electrolytes- hypernatemia , hypokalemia pH is elevated( hypokalemic alkalosis) Osmolality is elevated

25. Sex hormones & investigations in Infertility

26. Commonly measured hormones for evaluation of infertility are: FSH LH Testosterone Prolactin Estradiol Anti-Mullerian Hormone TSH Progesterone Inhibin-B

27. Assignment Questions( 5*4 = 20 marks) List the adrenal function test with significance of each. List the lab findings in adrenal hyperfunction. List the lab findings in adrenal hypofunction. In tabular form, give the pattern of hormone levels in various endocrine abnormalities in males and females.

28. Thank you