1. Cushing’s, Adrenal Insufficiency and Other Glucocorticoid Related Issues Family Practice Residency Program Waterloo, IA September 11, Janet 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
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
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
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. Urinary free cortisol baseline 2 mg 8 mg ACTH 300 µg 180 40 989 µg 991
Pituitary
Hyperfunction
Adrenal
Tumor
Ectopic
Production
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
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 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

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 µg ACTH (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. Stimulated cortisol 0.1 µg/dl
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. Stimulated cortisol 25 µg/dl
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.

51. Long-Term Therapy Hydrocortisone (10-15 mg/day)
Start with hydrocortisone and add florinef as needed.
Florinef ( mg/day)

52. Educate patient about use of steroid during “stress”
Yearly follow-up

53. Stress dose? Pulling wisdom teeth Colonoscopy Endometrial biopsy
Flu with aches and pains

54. Stress dose?
CABG
Hip replacement
Final exams
Death in the family

55. A 45 y.o. woman with RA has been treated with 10 mg of prednisone for 3 years. She will undergo laparoscopic surgery in 2 days. Her surgeon wants you to write pre-op orders.

56. Pituitary adrenal axis is suppressed
 ACTH due to exogenous glucocorticoid
Stopping glucocorticoid and/or stress of surgery could lead to adrenal crisis

57. Peri-Operative Corticosteroid Coverage
Minor surgical stress - usual dose day of procedure
Moderate surgical stress - 50 mg HC day of procedure then resume usual dose
Ann Surg 219:416, 1994

58. Peri-Operative Corticosteroid Coverage
Major surgical stress mg HC on day of procedure - 50 mg HC on post-op day 1
Resume usual dose unless clinical condition deteriorates
Ann Surg 219:416, 1994

59. Avoid too much glucocorticoid
After a stress dose rapidly resume the replacement dose
Don’t use cortisol or ACTH to try to monitor therapy

60. A 60 y.o. man has taken 60 mg of prednisone daily for 6 months for anterior ischemic optic neuropathy. His ophthalmologist has seen no improvement and wants to stop the steroid.

61. The Dilemma
Stopping the drug will lead to secondary adrenal insufficiency
He has muscle weakness and weight gain and his T score is The glucocorticoid needs to be stopped as rapidly as possible

62. Taper Option # 1 January 1 January 15 January 30 February 1
March 1
60 mg
40 mg
20 mg
10 mg
5 mg
Off

63. Taper Option # 2 January 1 January 15 February 1 March 1 April 1 60 mg
60 mg q.o.d.
30 mg q.o.d.
10 mg q.o.d.
Off

64. Taper Option # 3 January 1 January 2 February 1 March 1 April 1 May 1
etc. until off
60 mg
10 mg
9 mg
8 mg
7 mg
6 mg

65. Questions to Ask What is the reason for the taper?
Is it to avoid recurrence of disease?
Is it to avoid adrenal crisis?

66. Effect of Dose of Hydrocortisone on Mortality
RR % CI p
0<HC< ns
20<HC< ns
25<HC<
HC>
JCEM 94:4216, 2009

67. Take Home Points Remember glucocorticoid equivalencies
Use stress doses sparingly
When HPA axis is suppressed, taper slowly beginning at a maintenance dose

68. A 42 y.o. with a history of chronic back pain has severe fatigue and the lab pages you because his cortisol is 1.0 and his TSH is 1.4.

69. One of your patients takes 5 mg of prednisone daily after an organ transplant. She is having her wisdom teeth pulled tomorrow morning and calls to find out what to do about her prednisone since she will be NPO.