adrenal steroids

Question 1

glucocorticoid effects

Answer 1

• increase gluconeogenesis
• release aa through muscle catabolism
• inhibit peripheral glucose uptake
• stimulate lipolysis
• ** all to maintain adequate glucose for brain

anti-inflammatory effects:

• upregulate anti-inflamm proteins
• down regulate pro-inflamm proteins
• decrease leukocyte presence and function at sites of inflammation

Others

• fetal lung development
• cognitive function/CNS effects

Question 2

Adrenal Crisis

Answer 2

• volume depletion, hypotension, N + V, hyperkalemia, hyponatremia
• do not delay tx while waiting for definitive proof of dx
• fluid and sodium replacement (1-3 L of 0.9% NaCl +/- 5% dextrose in first 24 hrs)
• give isotonic saline **hypotonic saline will worsen hyponatremia
• high dose IV dexamethasone or hydrocortisone –> once PT is stable gradually taper to maintenance dose
• mineralcorticoids do not work acutely

Question 3

dx of adrenal insufficiency

Answer 3

• plasma cortisol at baseline then 30-60 mins after 250 micrograms of cosyntropin IV (synthetic ACTH)
• Normal: cortisol > 18 mg/dl
• abnormal: cortisol <18 mg/dl
• Primary: low cortisol, high ACTH
• secondary: low cortisol and ACTH

Question 4

tx of chronic primary adrenal insufficiency maintenance tx

Answer 4

• glucocorticoid replacement: 15-20 mg hydrocortisone on awakening and 5-10 mg in early afternoon
• mineralcorticoid replacement: 0.05-0.2 mg fludrocortisone, liberal salt intake

Question 5

tx of chronic primary adrenal insufficiency - minor febrile illness

Answer 5

• increase glucocorticoid dose 2-3 fold for the few days of illness, do not increase mineralcorticoid

Question 6

tx of chronic primary adrenal insufficiency - emergency tx of severe stress

Answer 6

• inject prefilled dexamethasone (4mg) syringe intramuscularly

Question 7

tx of primary adrenal insufficiency coverage for illness or sx

Answer 7

• mod illness: hydrocortisone 50 mg PO BID or IV
• severe illness: hydrocortisone 100 mg IV Q 8 hrs
• mod stressful procedures: 100 mg hydrocortisone IV before procedure
• major sx: 100 mg hydrocortisone IV before induction of anesthesia and then every 8 hrs for first 24 hrs

Question 8

dx of Cushing’s syndrome

Answer 8

• low dose Dexamethasone suppression test
• low ACTH= ACTH-independent Cushing’ –> adrenal tumor
• high ACTH= ACTH-dependent Cushing –> pituitary tumor or ectopic production –> high dose DEXA –> suppression (pituitary tumor) or non-suppressive (ectopic production)
• ectopic secretion will not decrease with Dexa bc the source is resistant to (-) feedback

Question 9

aminoglutethimide

Answer 9

• tx of Cushing’s
• blocks conversion of cholesterol to pregnenolone

**think: AA are so basic (cholestol –> pregnenolone is basic 1st step in steroid synthesis)

Question 10

ketoconazole

Answer 10

• tx of Cushing’s
• antifungal imadazole derivative –> inhibitor of adrenal and gonadal steroid synthesis

Question 11

mitotane

Answer 11

• tx of Cushing’s
• related to DDT insecticides –> cytotoxic action on adrenal cortex
• bad SE

**think: “mighty” = cytotoxic

Question 12

metyrapone

Answer 12

• tx and dx of Cushing’s
• inhibits 11-hydroxlation –> interferes with cortisol and corticosterone synthesis
• metryapone test: ACTH levels should rise and precursor 11-deoxycortisol should rise too

Question 13

mifepristone

Answer 13

• tx of Cushing’s
• glucocorticoid receptor antagonist
• causes generalized glucocorticoid resistance

**think: it presses on the receptor = antagonist

Question 14

primary aldosteronism screening test

Answer 14

• screen in PT with HTN and hypokalemia, or severe resistant-tx HTN
• plasma aldosterone concentration (PAC)
• plasma renin activity (PRA)
• PAC/PRA ratio > 20 ng/dL per ng/mL
• 24 hr urine collection for aldo and Na

Question 15

21-hydroxylase deficiency tx

Answer 15

• dx: increased response of 17-hydroxyprogesterone to ACTH stimulation (cosyntropin stimulation)
• steroids: dexamethasone, prednisone or hydrocortisone
• fludrocortisone in salt wasting
• giving steroids suppresses ACTH production and reduces overproduction of androgens

Question 16

toxicity of corticosteroids

Answer 16

• continued use of supraphysiologic steroid doses results in iatrogenic Cushing’s syndrome (daily doses >100 mg hydrocortisone for 2+ weeks)
• withdrawal of steroid tx resulting in adrenal insufficiency
• acute SE: insomnia, behavior changes, acute peptic ulcers, pancreatitis
• **unusual to have severe SE if used for less than 2 weeks

Question 17

complications of prolonged corticosteroid use

Answer 17

• HPA axis suppression
• peptic ulcer
• infections (thrush)
• decreased wound healing
• severe myopathy
• nausea
• depression
• glaucoma and cataracts
• benign intracranial HTN
• growth retardation in children
• osteoporosis
• suppression of ACTH –> shock state if abrupt withdrawal
• Iatrogenic Cushing’s
• hyperglycemia (due to increased gluconeogenesis)

Question 18

general considerations in clinical use of steroids

Answer 18

• glucocorticoids tend to make almost everyone feel better acutely
• try to use intermediate acting glucocorticoids
• do not decrease or stop dose abruptly
• alternate day tx to minimize SE of HPA suppression and iatrogenic cushings (but can’t suse in tx of adrenal insufficiency!)

Question 19

withdrawal from steroid tx

Answer 19

• adrenal HPA suppression can occur after 2 weeks
• PTs on long term tx should be assumed to have underlying adrenal insufficiency –> increase dose for stress and consider medical ID bracelet
• can take 2-12 mon for return of acceptable HPA axis function
• Hypothalamic pituitary function returns before adrenocortical function
• PTs at risk for adrenal crisis!!!

Question 20

tx of primary aldosteronism

Answer 20

• sx for unilateral adenoma
• medical- bilateral adrenal hyperplasia
• spironolactone or eplerenone

Question 21

Dexamethasone

Answer 21

• most potent anti-inflammatory action, longest duration of action (36-72 hrs)

tx:

• emergency tx of severe stress or trauma in primary adrenal insufficiency (prefilled IM injection)
• adrenal crisis (IV)
• Cushing’s dx (suppression test)