Adrenal Insufficiency and Cushing Syndrome

Question 1

cortisol production from zona _______ and _______ is controlled by ______ hormone ACTH whose secretion is regulated by the ______ from the ______

Answer 1

fasciculata; reticularis; pituitary; CRH; hypothalamus

Question 2

skin hyperpigmentation: what is in excess and how does this happen?

Answer 2

ACTH; MSH (melanocyte-stimulating hormone) is also a part of POMC precursor of ACTH

Question 3

how is cortisol inactivated in the kidney? why is this important?

Answer 3

it is converted to cortisone by 11beta-HSD2; protects the mineralocorticoid receptor on the tubules of the distal nephron from the action of cortisol (cortisol has the same affinity for mineralocorticoid receptors as aldosterone and cortisol circulates at a thousand times greater total concentration)

Question 4

what enzyme converts cortisone back into cortisol in end-organs?

Answer 4

11beta-HSD1

Question 5

dx: low cortisol, normal/low ACTH

Answer 5

secondary (pituitary) or tertiary (hypothalamus) adrenal insufficiency

Question 6

symptoms of primary adrenal insufficiency (4)

Answer 6

hypotension, skin hyperpigmentation, hyponatremia, hyperkalemia

Question 7

initial evaluation of suspected adrenal insufficiency

Answer 7

plasma cortisol and ACTH

Question 8

expected findings in primary adrenal insufficiency

Answer 8

low cortisol, high ACTH

Question 9

what medications could cause total cortisol levels to be high and why?

Answer 9

estrogen (oral contraceptives); increase in CBG

Question 10

treatment for primary adrenal insufficiency (2)

Answer 10

hydrocortisone, fludrocortisone (glucocorticoids)

Question 11

major differences between secondary and primary adrenal insufficiency (2)

Answer 11

1. in secondary adrenal insufficiency, ACTH may be low or inappropriately normal
2. in secondary adrenal insufficiency, RAAS system and zona glomerulosa remain intact so aldosterone synthesis is preserved

Question 12

most common cause of primary adrenal insufficiency in US

Answer 12

autoimmune

Question 13

if someone with primary adrenal insufficiency is negative for adrenal autoantibodies, what is the next test you should do?

Answer 13

adrenal CT

Question 14

3 major causes of Cushing syndrome

Answer 14

1. exogenous corticosteroids
2. primary adrenal adenoma
3. ACTH-secreting pituitary adenoma

Question 15

major difference between Cushing syndrome caused by primary adrenal adenoma vs. ACTH-secreting pituitary adenoma

Answer 15

adrenal adenoma: low ACTH

ACTH-secreting pituitary adenoma: high ACTH

Question 16

dx: high cortisol, unilateral enlargement of one adrenal gland

Answer 16

Cushing syndrome caused by adrenal adenoma

Question 17

3 diagnostic tests for Cushing syndrome

Answer 17

1. late-night salivary cortisol
2. overnight low-dose dexamethasone suppression test
3. 24 hour urine free cortisol: not for screening

Question 18

how does the dexamethasone suppression test work?

Answer 18

dexamethasone is a steroid that provides negative feedback to the pituitary to suppress the secretion of ACTH. this test can therefore distinguish between Cushing syndrome caused by a pituitary adenoma or ectopic ACTH secretion (i.e., small cell lung carcinoma)

Question 19

first test when you suspect Cushing syndrome

Answer 19

plasma ACTH

Question 20

1. dx: high cortisol + low ACTH

2. dx: high cortisol + high/normal ACTH

Answer 20

1. Cushing syndrome caused by adrenal adenoma

2. Cushing syndrome caused by pituitary adenoma or ectopic ACTH