Cushing's Syndrome

Question 1

MCC of Cushings syndrome

Answer 1

exogenous cortisol (steroid supplementation; think COPD)

Question 2

What is Cushing’s disease?

Answer 2

high cortisol due to elevated anterior pituitary secreted ACTH (pituitary adenoma)

Question 3

What is ectopic cushings syndrome?

Answer 3

high cortisol due to non-pituitary secreted ACTH (small cell lung cancer, carcinoid tumor)

Question 4

What are the current 3 types of Cushings syndromes?

Answer 4

1. ACTH- Dependent (high ACTH due to cushings disease or ectopic cushings or CRH syndrome)
2. ACTH-Independent (low ACTH; due to adrenal adenoma/carcinoma, micronodular hyperplasia)
3. Pseudo-Cushings (major depression, alcoholism)

Question 5

Screening tests for cushings?

Answer 5

Low dose dexamethasone suppression
- 1mg given; positive if cortisol > 1.8 mcg/dL (50 nmol/L)

24 hour urinary free cortisol (test at least twice)
- positive if > 3x normal

Late night salivation cortisol test (test at least twice)

• positive if elevated
• -normally diurnal and low

Question 6

Confirmatory tests for Cushing’s?

Answer 6

Late afternoon or midnight ACTH levels

• < 5 pg/dL = ACTH independent (adrenal adenoma)
• 5-10 pg/dL indeterminate
• > 15 pg/dL ACTH dependent (pituitary adenoma; will need to do additional testing!!!)

Question 7

What additional testing is needed if suspected ACTH dependent Cushing’s?

Answer 7

High dose dexamethasone test (8mg)

• > 50% suppression of ACTH = likely pituitary adenoma
• <50% suppression = likely ectopic Cushings (MCC lung cancer)

Question 8

How does Cortisol Releasing Hormone test affect the following:

Cushing syndrome
Psuedo-Cushing
Pituitary adenoma
Ectopic etiology

Answer 8

Cushing syndrome: cortisol will increase

Psuedo-Cushings: cortisol will be low

Pituitary adenoma: ACTH and cortisol will rise

Ectopic etiology: no response in ACTH or cortisol

Question 9

Peri-operatively, what must be administered to a patient?

Answer 9

stress-dose steroids for glycemic and BP control; want to avoid adrenal insufficiency

Question 10

what are 4 medical therapies for unresectable cushings disease/syndome?

Answer 10

1. aminoglutehimide (inhibits cholesterol conversion to pregnenolone)
2. Metyrapone (inhibits 11-beta hydroxylase)
3. Ketoconazole
4. Mifepristone (cortisol and progesterone blockers)

Question 11

What is Nelsons syndrome?

Answer 11

pituitary tumor post bilateral adrenalectomy

• usually chromophobe adenoma
• elevated ACTH w/o negative feedback
• hyperpigmentation, HAs, visual changes