1. Endocrine Physiology The Adrenal Gland 2 Dr. Khalid Al-Regaiey

2. Produced by the fasciculata and reticularis layers of the adrenal cortex Glucocorticoids (cortisol): recognized early to increase plasma glucose levels: Mobilization of amino acids from proteins Enhance liver gluconeogenesis Target tissues: most body tissues Glucocorticoids

3. CRH from hypothalamus is the major regulator of ACTH secretion ADH is also a potent ACTH secretagogue ACTH from anterior pituitary stimulates cortisol synthesis and secretion CRH (and ACTH) are secreted in pulses The greatest ACTH secretory activity occurs in the early morning hours and diminish late in the afternoon. Glucocorticoids (cont.)

4. HPA Axis

5. Primary and secondary hypersecretion of cortisol

6. After ACTH has been produced, cortisol will be evident 15 to 30 minutes later There are usually 7-15 episodes per day There is a major burst in the early morning before awakening.

7. Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers: Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2%) To cross the target tissue membrane, the hormone must dissociate from its carrier protein

8. Regulation of Cortisol release

9. Regulation of Cortisol Release cont Enhanced release can be caused by: physical trauma infection extreme heat and cold exercise to the point of exhaustion extreme mental anxiety

10. Increases blood glucose levels by: (+) glucogenesis in the liver via stimulating the enzymes involved in glucogenesis. Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells.

11. Reduces protein formation Occurs everywhere EXCEPT liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells ↓ protein synthesis & ↑ amino acid blood levels These high blood amino acid levels are transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

12. Lipolytic. Mobilizes fatty acids & glycerol from adipose tissue lead to ↑ their blood concentrations makes more glycerol available for glucogenesis. Fat broken down & less formed due to less glucose transported into fat cells. Redistribution of body fat: ↑ formation of fat in trunk areas & face ↓ fat (& muscle) from extremities Increases appetite

13. Anti-inflammatory Stabilizes lysosomal membrane Reduces degree of vasodilatation Decreases permeability of capillaries Decreases migration of white blood cells Suppresses immune system

14. Decrease production of eoisinophils and lymphocytes Suppresses lymphoid tissue systemically therefore decrease in T cell and antibody production thereby decreasing immunity Decrease immunity could be fatal in diseases such as tuberculosis Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection.

15. Maintains body fluid volumes & vascular integrity Cortisol levels vary with water intake Cortisol has mineralcorticoid effect, Not as potent as aldosterone. BP regulation & cardiovascular function: Sensitizes arterioles to action of noradrenaline (Permissive effect). Decreased capillary permeability Maintains normal renal function

16. Negative feedback control on release of ACTH Modulates perception & emotion Mineral metabolism: Anti-vitamin D effect GIT: Increases HCl secretion

17. Permissive regulation of fetal organ maturation Surfactant synthesis (phospholipid that maintains alveolar surface tension). Inhibition of linear growth in children due to direct effects on bone & connective tissue

18. Cushing’s Syndrome Cushing’s syndrome results from continued high glucocorticoid levels 3rd - 6th decade, 4 to1 females Causes: pharmocologic pituitary adenoma 75-90% adrenal adenoma, carcinoma ectopic ACTH

19. Cushing’s Syndrome Signs: Fat is deposited in the body trunk (central obesity) Buffalo hump Moon facies (subcutaneus fat in cheeks and submandibular) Purple striae Blood-glucose levels rises chronically, causing adrenal diabetes May cause beta cells to die

20. Purple striae Cushing’s Syndrome

21. treatment based on cause Cushing’s Syndrome

22. Adrenocortical insufficiency primary causes, ie. Addison’s disease autoimmune disease, tumors, infection, hemorrhage, metabolic failure, ketoconazole secondary causes hypopituitarism, suppression by exogenous steroids

23. Adrenocortical insufficiency symptoms, signs fatigability, weakness, anorexia, nausea, weight loss, hyperpigmentation, hypotension, women loss of axillary and pubic hair can lead to severe volume depletion and shock Reduced cortisol results in poor blood glucose regulation Patient cannot cope with stress Adrenal crisis: asthenia, severe pains in the abdomen, vascular collapse….

24. treatment glucocorticoid replacement, mineralocorticoid replacement Adrenocortical insufficiency