013015 adrenal insuff, cushing syndrome

Question 1

effects of cortisol

Answer 1

synchronizes circadian clock
immune and inflam
gluconeogenesis, lipolysis, proteolysis
increase appetite
depression, anxiety
growth and reproduction
cardiovascular tone

Question 2

symptoms of adrenal insufficiency

Answer 2

fatigue
GI-nausea, vomiting, anorexia, weight loss
hypotension-dizziness, orthostasis
increased skin pigmentation (primary adrenal insuff)
salt craving (primary adrenal insuff)

Question 3

lab abnormalities in adrenal insufficiency

Answer 3

hyponatremia
hyperkalemia (primary adr insuff)
lymphocytosis

Question 4

imaging abnormalities for adrenal insuff

Answer 4

bilateral adrenal enlargement

pituitary mass

Question 5

what drugs can cause adrenal insuff

Answer 5

ketoconzaole, etomidate, mitotane, metyrapone

mifepristone (glucocorticoid receptor antagonist)

Question 6

how do you diagnose adrenal insuff?

Answer 6

plasma cortisol an hour after cosyntropin (ACTH analogue) stimulation

look at CBC, serum sodium, potassium, creatinine, urea, TSH

Question 7

what is the value of the cosyntropin stimulation test?

Answer 7

it evaluates for maximum adrenocortical secretory capacity and tests for adrenal destruction (primary insufficiency) or adrenal atrophy (secondary adrenal insuff)

Question 8

once we see that the cortisol levels are low and the cosyntropin stimulation test gives low cortisol, how do you determine the cause of adrenal insufficiency?

Answer 8

slide 15

Question 9

most common cause of primary adrenal insuff

Answer 9

autoimmune adrenalitis

Question 10

blood cortisol test looks at

Answer 10

free and bound cortisol

Question 11

causes of secondary adrenal insuff

Answer 11

withdrawal from exogenous corticosteroid therapy

pituitary/hypothalamic disease (hypophysitis)

Question 12

tx for primary adrenal insuff

Answer 12

hydrocortisone-authentic cortisol (important: plasma ACTH should remain elevated even with adquate hydrocortisone-low/normal levels may reflect overreplacement)

fludrocortisone-aldosterone equivalent

Question 13

tx for secondary adrenal insuff

Answer 13

hydrocortisone (less needed than in primary adr insuff b/c there is usually still some cortisol secretion from adrenals)

Question 14

cushing’s syndrome symptoms

Answer 14

weight gain
proximal muscle weakness
hirsutism/androgen excess in women
violaceous striae
cutaneous wasting
easy bruising
facial fullness
diabetes
osteoporosis
increased BP
myopathy
neuropsych disorders
edema
hypogonadism
growth retardation (in children)

Question 15

physiologic hypercortisolism

Answer 15

due to stress, alcohol, neuropsych disorders, starvation

Question 16

what diagnosis could raise your suspicion for Cushing syndrome

Answer 16

diabetes/hypertension/metabolic syndrome
osteoporosis
adrenal nodules

Question 17

how do you diagnose Cushing’s syndrome

Answer 17

if Cushing syndrome is suspected, need exclude exogenous glucorticoid exposure first

then perform one of the following tests:

• -24 hour urine cortisol (not very sensitive)
• -overnight DST (dexamethasone)-many false positives
• -late night salivary cortisol

if the test result is abnormal, you need to exclude physiologic causes of hypercortisolism

Question 18

what are possible causes of Cushing syndrome?

Answer 18

ACTH dependent:

• ACTH secreting pituitary tumor (Cushing’s dis)
• non-pituitary ACTH secreting tumor (ectopic ACTH)

ACTH independent:

• -exogenous glucocorticoid therapy-most common cause of Cushing syndrome
• -adrenal adenoma or carcinoma
• -nodular adrenal hyperplasia (bilateral)

Question 19

how can you diagnose the cause of tCushing syndrome

Answer 19

measure plasma ACTH

see slide 38

Question 20

tx for Cushing syndrome

Answer 20

surgery-remove tumor (pituitary, adrenal)

bilateraly adrenalectomy is indicated in pts who have failed other modalities of tx. definitive tx but then would depend on steroids for life

radiotherapy (for pituitary Cushing if surgery fails)

pituitary-directed: pasireotide (somatostatin receptor agonist) and cabergoline (dopamine receptor agonist) if surgery fails

adrenal steroidogenesis inhibitors:

• -ketoconazole
• -metyrapone
• -mitotane (used in adrenal cancer)
• -etomidate

glucocorticoid receptor antagonist:
–mifeprisone

Question 21

in primary adrenal insuff, what can you see in the adrenal glands?

Answer 21

massive bilateral adrenal enlargement (due to trophic effects of ACTH)