Adrenal gland

2. Adrenal gland

4. The adrenal cortex produces three major classes of steroids: (1) glucocorticoids (2)mineralocorticoids (3) adrenal androgens

5. Adrenal cortex • Zona glomerulosa (Aldrosterone) • Zona Fasciculata (Cortisol) • Zona reticularis( Androgen)

9. Cholesterol, derived from the diet and from endogenous synthesis, is the substrate for steroidogenesis. • Uptake of cholesterol by the adrenal cortex is mediated by the low-density lipoprotein (LDL) receptor. • The principal glucocorticoid is cortisol (hydrocortisone).

11. Glucocorticoid Physiology

12. Glucocorticoid • regulation of protein, carbohydrate, lipid and nucleic acid metabolism. • Glucocorticoids raise the blood glucose by antagonizing the secretion and actions of insulin, inhibiting peripheral glucose uptake, it promotes gluconeogenesis. • protein breakdown and nitrogen excretion, inhibition of protein synthesis.

13. Glucocorticoid • Glucocorticoids have anti-inflammatory properties. • Cortisol impairs cell mediated immunity. • Cortisol has major effects on body water. It helps regulate the Extra Cellular Fluid Volume by retarding the migration of water into cells and by promoting renal water excretion, the latter effect mediated by suppression of vasopressin secretion, by an increase in the rate of glomerular filtration, and by a direct action on the renal tubule.

15. Mineralocorticoid Physiology

16. Renin-Angiotensin- Aldosterone system • Renin is a proteolytic enzyme that is produced in the granules of the juxtaglomerular cells surrounding the afferent arterioles of glomeruli in the kidney. • Renin acts on the angiotensinogen (in the liver) to form the angiotensin I . • Angiotensin I is then enzymatically transformed by angiotensin-converting enzyme (ACE), which is present in many tissues (particularly the pulmonary vascular endothelium), to the angiotensin II.

17. Angiotensin II is a potent pressor agent and exerts its action by a direct effect on arteriolar smooth muscle. • angiotensin II stimulates production of aldosterone by the zona glomerulosa of the adrenal cortex.

18. mineralocorticoids are considered major regulators of ECFV and are the major determinants of potassium metabolism. These effects are mediated by the binding of aldosterone to the MR in epithelial cells, primarily the principal cells in the renalcortical collecting duct.

19. Regulation of Aldosterone Secretion • renin-angiotensin system, • potassium • ACTH

20. Potassium ion directly stimulates aldosterone secretion, independent of the circulating renin-angiotensin system, which it suppresses . • Potassium modifies aldosterone secretion indirectly by activating the local renin-angiotensin system in the zona glomerulosa.

23. Androgen physiology

24. Androgens regulate male secondary sexual characteristics and can cause virilizing symptoms in women. • Adrenal androgens have a minimal effect in males whose sexual characteristics are predominately determined by gonadal steroids (testosterone). • In females several androgen-like effect( sexual hair) are mediated by adrenal androgens.

25. Hyperfunction of the Adrenal Cortex • Excess cortisol is associated with Cushing's syndrome • Excess aldosterone causes aldosteronism • Excess adrenal androgens cause adrenal virilism.

26. Causes of Cushing's Syndrome

27. Pituitary-hypothalamic dysfunction • Pituitary ACTH-producing micro- or macroadenomas • ACTH or CRH-producing non endocrine tumors (bronchogenic carcinoma, carcinoid of the thymus)

28. Adrenal macronodular hyperplasia • Adrenal micronodular dysplasia • Adrenal neoplasia(adenoma or carcinoma) • Exogenous (Prolonged use of glucocorticoids or ACTH)

29. Sign or Symptom • Typical habitus (centripetal obesity ;Increased body weight) • Fatigability and weakness • Hypertension • Hirsutism • Hypertrophy of clitoris • Amenorrhea • Broad violaceous cutaneous striae

30. Personality changes • Ecchymoses • Proximal myopathy • Edema • Polyuria, polydipsia • Hyperglycemia

35. Diagnosis • The diagnosis of Cushing's syndrome depends on the demonstration of increased cortisol production and failure to suppress cortisol secretion normally when dexamethasone is administered.

36. Diagnosis • Cortisol after dexamethazone suppression test • ACTH • Urine 24 hours for cortisol • CT-scan and MRI of pituitary or adrenal

37. Treatment of Cushing's Syndrome • Trans sphenoidal resection of pituitary microadenoma • Radiation therapy • Bilateral adrenalectomy • Medical adrenalectomy (metyrapone, mitotane, aminoglutethimide, ketoconazole)

39. Adrenal insufficiency • Idiopathic • Infection • Surgery • Congenital • Hypothalamic and pituitary disease • exogenus

42. Sign and Symptom • Weakness • Pigmentation of skin • Wieght loss • Anorexia,nausea and vomiting • Hypotension and syncope

46. Diagnosis • Check sodium and potassium • blood sugar • cortisol after ACTH stimulation test

47. ACTH stimulation test(250ug)

48. Treatment -Steroid and mineralocorticoid

50. Hyper Aldosteronism • Aldosteronism is a syndrome associated with hyper secretion of the mineralocorticoid aldosterone. • Inprimaryaldosteronism the cause for the excessive aldosterone production resides within the adrenal gland. • Insecondaryaldosteronism the stimulus is extra adrenal.