Janet A. Schlechte, M.D.

1. Cushing’s, Adrenal Insufficiency and Other Glucocorticoid Related IssuesFamily Practice Residency ProgramWaterloo, IASeptember 11, 2013Janet A. Schlechte, M.D.

2. Disclosure of Financial Relationships Janet A. Schlechte, M.D. has no relationships with any proprietary entity producing health care goods or services consumed by or used on patients.

3. Objectives • Approach to glucocorticoid excess • Management of adrenal insufficiency • Peri-op management of glucocorticoids • Steroid taper

5. Cushing’s Syndrome Causes • ACTH secreting pituitary tumor • Adrenal adenoma/carcinoma • Ectopic ACTH production • Exogenous glucocorticoid

9. Classic Features of Cushing’s • Centripetal obesity • Violaceous striae • Proximal muscle weakness • Amenorrhea • Thin skin • Bruising

13. Other Features of Cushing’s • Hypertension • Glucose intolerance • Diabetes • Hypokalemia • Bone loss

14. Causes of Cushing’s Syndrome • ACTH secreting pituitary tumor • Adrenal adenoma/carcinoma • Ectopic ACTH production • Exogenous glucocorticoid

15. Pituitary versus Adrenal Cushing’s

16. Ectopic ACTH Secretion • Severe hypokalemia • Metabolic alkalosis • Muscle weakness • Few of the classic stigmata • Hyperpigmentation

18. Cushing’s Syndrome • Rare disorder • How often will it present in the primary care setting?

19. Many people complain of weight gain and bruising but few have Cushing’s • Even astute clinicians should screen for glucocorticoid excess

20. Screening Tests • 24 hour urine cortisol • 1 mg dex test • 11 p.m. salivary cortisol

21. 24 Hour Urine Cortisol • Inconvenient but most sensitive • May need to do more than one unless results are 2-3x normal • Occasional false positives

22. Diurnal Variation of Cortisol Pre-Dex Cortisol Post-Dex Time

23. 1 mg Dex Test • 1 mg dexamethasone at 11 p.m. and measure 8 a.m. cortisol the next day • Healthy subjects will have cortisol <2 µg/dl

24. 1 mg Dex Test • false positives - dilantin - obesity - estrogen - stress - depression

25. A 30 y.o. woman has gained 20 pounds over the last six months. She has also noted leg swelling and her blood pressure is harder to control. She takes HCTZ and a BCP.B/P 140/100, BMI 35, bruises on legs, buffalo hump, pale pink striae.

26. She has read about Cushing’s syndrome and is worried about a pituitary tumor • Potassium 3.8, A1C 5.6%, CBC nl

27. She takes 1 mg of dex at 11 p.m. and an 8 a.m. cortisol the next day is 10 µg/dl. • Does she have Cushing’s?

28. She collects a 24 hour UFC and the result is 53 µg/dl (<50) • Does she have Cushing’s?

29. A 40 y.o. man has poorly controlled hypertension. His weight has increased by 50 lb in the last year. He has bright purple striae and significant muscle weakness. A 1 mg DST shows a cortisol of 20 so screening test is positive.

30. To rule out a false positive do confirmatory test • He collects a 24 hour UFC and the value is 350 µg/dl (<50) • Test is positive – he has Cushing’s • Now what?

31. When cortisol excess is confirmed draw ACTH ACTH  Pituitary tumor Adrenal tumor Ectopic

32. Glucocorticoid Excess Screening Test Normal Abnormal Confirm Test Stop Abnormal Normal Get ACTH Stop Undetectable Elevated Adrenal Pituitary Ectopic Do DST to differentiate

33. ACTH Cortisol ACTH Cortisol ACTH Cortisol Adrenal Tumor Ectopic Production Pituitary Hyperfunction Urinary free cortisol baseline 2 mg 8 mg ACTH 300 µg 180 40 989 µg 991 990 undet. 4034 µg 4000 3989

34. A 41 y.o. collapsed on the golf course in August. For 6 months he has been tired with intermittent nausea, abdominal pain and deterioration of his golf game. In the ER his BP was 60/- with a pulse of 130. He has a deep tan, pigmented buccal mucosa, a small thyroid and a normal neuro exam.

35. In The ER • Sodium 125 • Potassium 6.4 • Chloride 98 • CO2 18 • Creatinine 1.4 • Glucose 75

36. Features of Primary AI • Hyperpigmentation • Fatigue and weakness • Hypotension • Postural dizziness • Abdominal pain • Weight loss

37. Causes of Primary Adrenal Insufficiency • Autoimmune • Adrenal hemorrhage • Granulomatous disease

42. Your working diagnosis is primary adrenal insufficiency. • How do you confirm your suspicion?

43. Cortrosyn stimulation test - Measure plasma cortisol before and 1 hour after IM injection of 250 µgACTH (cortrosyn)

44. Short Cortrosyn Stimulation Test Cortisol Normal 1° AI

45. After cortrosyn stimulation test begin steroid replacement. • Little practical reason to start dexamethasone before cortrosyn.

46. After the cortrosyn test the IV saline is continued and you give the 100 mg of hydrocortisone. One hour later the lab calls with the cortisol results. • Basal cortisol 0.1 µg/dl • Stimulated cortisol 0.1 µg/dl

47. What if the results were • Basal cortisol 9 µg/dl • Stimulated cortisol 25 µg/dl

48. Classical Glucocorticoid Equivalents Daily Replacement Doses 5 mg Prednisone 20-25 mg Hydrocortisone 0.75 mg Dexamethasone 37.5 mg Cortisone acetate

49. More Physiologic Equivalents Daily Replacement Doses 5 mg Prednisone 10-15 mg Hydrocortisone 0.75 mg Dexamethasone

50. Treatment Guidelines • Monitor therapy clinically and with electrolytes. • Can’t use ACTH or cortisol to monitor therapy. • Consider other autoimmune disease.