The Adrenals

1. The Adrenals דר. אביטל נחמיאס

2. The Adrenals • Structure and function • Cortex • Hypofunction – Addison • Hyperfunction – Cushing • Adrenal incidentaloma

3. The Adrenal Glands בלוטת יותרת הכליה היא איבר רטרופריטוניאלי שנראה כמו כובע משולש מעל כל כליה המשקל של כל בלוטה הוא כ-4 גרם והמידות הן 2-3 X 4-6 cm

4. The Adrenal Glands Retroperitoneal 4 gr weight 2X4X1 cm

5. The Adrenal Glands

6. Morphology of the Adrenal Cortisol DHEA Aldosterone Cathecholeamines Medulla Reticularis Fasciculata Glomerulosa

7. Adrenal Cortex Zona glomerulosa- 15% Mineralocorticoid - Aldosterone Zona fasciculata- 75% Glucocorticoid - Cortisol and DHEA Zona reticularis- 10% Androgens - DHEA (DeHydroEpiAndrosterone), DHEAS DHEAS הוא ההורמון הפעיל שאחראי על כל סימני הויריליזציה

9. Actions of glucocorticoids • Immune system • ↑ WBC, ↓Eos, ↓ phagocytosis, anti inflammatory • Metabolic • Increase gluconeogenesis • Inhibit glucose uptake and utilization (NOT in brain, heart, liver, RBC) • Increase lipolysis, increase protein catabolism - myopathy • Impaired wound healing (less colagen production, impaired fibroblast function) • Inhibit osteoblasts (osteoporosis), ↓ intestinal and renal calcium absorption – increases PTH • Developmental • Differentiation of organs in the fetus • Complex action on the brain - arousal and cognition

10. Action of mineralocorticoids • Increased Na absorption in the kidney – water comes with the Na – fluid overload – hypertention and edema • K+ secreted instead of the Na – hypokalemia

11. Action of androgens

12. Regulation of cortisol secretion

13. Regulation of aldosterone secretion • RAS • K+ • ACTH

14. Regulation of androgen secretion • Adrenal androgen secretion is regulated by ACTH • In males – adrenal androgens have minimal effects • In females – adrenal androgens convert to testosterone in extraglandular tissues

15. Laboratory evaluation of adrenal function What’s the problem?

16. Cortisol circadian rhythm

17. Laboratory evaluation of adrenal function • Point measurements – at peak or trough • Urinary excretion • Dynamic testing • Stimulation – for suspected deficiency • Suppression – for suspected excess

18. Stimulation tests • Cortisol • ACTH (synacthen test) • Aldosterone • Volume depletion • Salt restriction • Diuretic administration • Upright posture

19. Suppression test • Cortisol • Dexamethasone suppression test • Aldosterone • Saline infusion test

20. Addison’s disease

21. Adrenal Failure • Primary (Addison’s Disease) Adrenal dysfunction Both GC and MC deficiency; ACTH. • Secondary Pituitary Dysfunction Only GC deficiency;ACTH.

22. “general languor and debility, feebleness of the heart's action, irritability of the stomach, and a peculiar change ofthe color of the skin" Thomas Addison The first description of Addison’s disease

24. Etiology of Addison’s Disease Autoimmune (80%) Isolated, Autoimmune polyglandular syndrome Type 1&2 Infections TB (calcifications), Histoplasmosis, CMV, HIV, syphillis, coccidioidomycosis, and cryptococcosis. Infiltration Amyloidosis, Hemochromatosis Hemorrhage Anticoagulants, trauma, sepsis, surgery, pregnancy, Meningococcemia causes waterhouse friderichsen syndrome – adrenal crisis) Infarction (bilateral – rare)

25. Etiology of Addison’s Disease • Bilateral Metastasis, Lymphoma (rare) • Bilateral adrenalectomy • Drugs • Inhibitors of steroidogenesis (ketoconazol) • Increase metabolism of steroid hormones (tegretol) • Congenital Adrenal Hyperplasia • Familial GC deficiency

26. Secondary Hypoadrenalism (ACTH) • Iatrogenic • Abrupt withdrawal of Chronic steroid Rx • Pituitary • Tumor (stalk effect) • Radiation • Surgery • Infarct • Hemorrhage • Sheehan syn – low BP during birth +/- hemorrhage

27. Autoimmune Addison’s Disease • Autoimmune Polyglandular Syndrome Type 1 • AR inheritance • More common in Iranian Jews • Hypoparathyroidism • Chronic Mucocutaneous Candidiasis • Gonadal failure • Addison • Ab in serum can be sent abroad

28. Autoimmune Addison’s Disease • Autoimmune Polyglandular Syndrome Type 2 • 50:1,000,000 rare • More common in women, age 30-50 • DM type 1 • Vitiligo • Graves or hashimoto • Addison • Pernicious anemia

29. Clinical Features of Adrenal Insufficiency Chronic syndrome Symptoms (not specific): Weakness & fatigue 100% Anorexia 100% Gastrointestinal symptoms 92% Signs: Weight loss 100%Hyperpigmentation (primary) 92% Hypotension 88% Salt craving (primary) 19% Postural hypotension symptoms 12% Asthenia

30. Hyperpigmentation ל ACTH ברמות גבוהות יש פעילות של MSH הורמון המפעיל מלנוציטים

31. Pigmented Scar

32. Buccal Hyperpigmentation

33. Laboratory Findings • Normocytic normochromic anemia (chronic disease) • Neutropenia and eosinophilia, relative lymphocytosis • Hyponatremia (SIADH, MC def) (90%) • Hyperkalemia (65%) • Hypoglycemia (rare) • Hypercalcemia (rare)

34. Diagnosis • Primary adrenal insufficiency: • Rapid ACTH test (Synacthen 250 mg) • Post-stimulation cortisol (30’ 60’) above 550 nmol/l (20 mg/dl) is normal, Below 200 could be addison • Plasma ACTH levels • Secondary/ tertiary adrenal insufficiency: • CRH test

36. Acute Syndrome (Addisonian Crisis) • Withdrawal • Acute stress • Infection • trauma • Surgery • Dehydration • Acute syndrome • Hemorrhage • Infarct • Meningococcemia (Waterhouse-Friderichsen syndrome) • Rare in secondary adrenal insufficiency.

37. Acute Syndrome (Addisonian Crisis) • Manifestations: • Shock and hypotension • Weakness, fatigue, lethargy • Muscle, joint and abdominal pain (acute abdomen) • Fever, anorexia, vomiting • Apathy, Clouded sensorium • Hypoglycemia is rare • The diagnosis should always be considered in any patient with unexplained shock

38. Treatment This is a life threatening emergency!!! • Acute Crisis • Hydrocortisone 100 mg IV, every 6-8 hours for 24 hr not PO !!! • Correct volume depletion, dehydration, hypotension • and hypoglycemia with IV saline and glucose • Correct precipitating factors, especially infection • As soon as the patient is eating and drinking and off IV fluids add fludrocortisone.

39. Maintenance • Hydrocortisone 15-20 mg in the morning & 5-10 mg at 4-6 PM or prednisone 5-7.5 mg orally once a day • Fludrocortisone 0.05-2 mg/day (primary) • Follow clinical symptoms, weight, B.P., electrolytes • Educate patient to increase cortisol dose during stress

40. Cushing’s disease Harvey Williams Cushing

41. Etiology of Cushing’s syndrome (CS) Exogenous: (Iatrogenic, Factitious) Endogenous: ACTH dependent: Pituitary (68%) Ectopic ACTH (SCLC)(15%) CRH rare ACTH independent: Adenoma (9%) Carcinoma (8%) Nodular hyperplasia rare Cushing’s disease

42. Pituitary tumor

43. Adrenal tumor

44. Ectopic ACTH secretion *hypokalemia

45. Symptoms and signs

46. Cushing’s Syndrome- Symptoms Feature % Weight gain 91 Hirsutism, acne 82 Menstrual disturbances/Dec. libido 76 Psychiatric dysfunction 60 Back pain 43 Muscular weakness 29 Fractures (osteoporosis)  Infections

47. Cushing’s Syndrome- Signs Feature % Central obesity (viceral fat) 97 Plethora 94 Moon face 88 HTN 74 Easy bruising (colagen fibroblasts) 62 Red striae 56 Muscle weakness 56 Edema 50

48. Moon Face and Plethora

49. Moon Face, hirsutism & Supraclavicular Fat Pads

50. Centripetal ObesityProximal Muscle Wasting