Adrenal 2 (Cushing's)

Question 1

Syndrome of ANY excess Cortisol state

Answer 1

Cushing’s SYNDROME

Question 2

Syndrome of excess Cortisol BECAUSE of ACTH-producing Pituitary Adenoma

Answer 2

Cushing’s DISEASE

*“syndrome” is any state, but “disease” is specifically due to tumor

Question 3

MOA of Cushing’s DISEASE

Answer 3

ACTH producing Pituitary tumor–> elevated Cortisol

Question 4

How can excess of Cortisol also result in excess Aldosterone and Androgens?

Answer 4

Can overwhelm cortisol-cortisone shunts in kidney, allowing the excess cortisol to cross-react with aldosterone and androgen receptors

Question 5

Steps to diagnosing Cushing’s Syndrome

Answer 5

1) Measure cortisol & confirm hypercortisolism

2) Localize the source by measuring plasma ACTH
- if high –> ACTH-dependent
- if low –> ACTH-independent Cushing’s Syndrome –> adrenal gland imaging

3) if ACTH-dependent, give HIGH dose dexamethasone to measure cortisol
- if still high –> Ectopic ACTH tumor
- if low (<5 mcg/dl) –> Cushing’s DISEASE (pituitary tumor)

Question 6

What are 3 tests to confirm Hypercortisolism?

Answer 6

24-hour urinary free cortisol*
LOW-dose dexamethasone suppression test*
Salivary free cortisol

*most reliable

Question 7

How does the low dose Dexamethasone administration test help with diagnosing Cushing’s Syndrome?

Answer 7

Acts as a steroid, so it should suppress Cortisol synthesis in normal patients

Question 8

If you have high Cortisol but low ACTH, what is the diagnosis?

Answer 8

Adrenal secreting adenoma

*usually benign

Question 9

You determine that there is high Cortisol. What is the next step to diagnosing Cushing’s Syndrome

Answer 9

Measure ACTH (determine if due to high ACTH or adrenal source of cortisol)

*if elevated, give HIGH dose dexamethasone to see response

Question 10

Purpose of the HIGH dose Dexamethasone Suppression Test in evaluating ACTH-dependent Cushing’s Syndrome

Answer 10

Differentiate between Pituitary vs. Etopic ACTH production

*Pituitary responds (decreased cortisol), ectopic doesn’t

Question 11

Treatment for a ACTH-Secreting Pituitary Tumor

Answer 11

Surgery (#1 tx)
ACTH synthesis blockers or steroid biosynthesis blockers
Bilateral Adrenalectomy

Question 12

Treatment for a Primary Adrenal Tumor

Answer 12

Surgery (#1 tx)
Steroid biosynthesis blockers
Adrenolytic drugs

Question 13

Treatment for Ectopic ACTH Syndrome

Answer 13

Surgery (#1 tx)
Steroid biosynthesis blockers
Bilateral Adrenalectomy

Question 14

ACTH secretion/synthesis blocking drugs (2 total)

Answer 14

Cabergoline

Pasireotide

Question 15

Cabergoline & Pasireotide exert their effect on

Answer 15

pituitary tumor

Question 16

With Cabergoline & Pasireotide, you will see ____ ACTH and _____ cortisol

Answer 16

decreased, decreased

Question 17

Steroid synthesis blockers (2 total)

• inhibition of steroidogenesis

Answer 17

Ketoconazole

Aminoglutethimide

Question 18

Ketoconazole & Aminoglutethimide exert their effect on

Answer 18

Adrenal Glands

Question 19

Glucocorticoid and Mineralocorticoid blockers (2 total)

Answer 19

Spironolactone

Mifepristone

Question 20

Spironolactone & Mifepristone exert their effect on

Answer 20

target tissues

Question 21

With Spironolactone & Mifepristone, you will see _____ cortisol

Answer 21

increased

• b/c the drugs are just blocking cortisol action/binding not its synthesis

Question 22

Just like CAH, ACTH-dependent cushing’s syndrome can have

Answer 22

hyperplastic adrenal glands

Question 23

Clinical features of hypercortisolism

Answer 23

• muscle wasting, weakness
• easy bruising, poor wound healing
• decreased bone formation, osteoporosis, fractures
• central obesity
• diabetes
• psychiatric disturbances