Adrenal Pharm Flashcards
What are glucocoritcoid target tissues? (4)
Adipose, liver, muscle, CNS
What are mineralocorticoid target tissues? (3)
Kidney, colon, sweat glands
What is the name of synthetic ACTH?
Tetracosactide
What is the short ACTH stimulation test? What is a normal result?
Measure blood cortisol before and after 250 mcg tetracosactide (synthetic ACTH). Normal: 1 hr later, cortisol > nl level + has at least doubled.
What is done if the short ACTH stim test is abnormal? Why?
Long ACTH stimulation test b/c pituitary may be functioning but with smaller response than normal
How does the long ACTH stimulation test work?
1 mg tetracosatide w mult administrations. Blood levels taken 1, 4, 8, and 24 hours later
What long ACTH stim test result would be expected with primary Addison’s disease?
Cortisol level reduced at all timepoints.
What long ACTH stim test result would be expected with secondary corticoadrenal insufficiency (adrenal is small but still responsive)
Delayed but normal response (increased cortisol)
How does the urine test for hypercortisolism work? How many tests are required?
Tests FREE cortisol in 24 hr sample. High = overwhelms metabolic conversion to inactive cortisone, > 2 tests = hypercortisolism.
How does the late night salivary cortisol test work?
Loss of circadian rhythm + absence of late night nadir on >2 tests suggests Cushing’s syndrome
How should hypercortisolism be tested in pregnant women?
Urine free cortisol test.
How should hypercortisolism be tested in epileptic patients?
Urine or salivary cortisol. Do not use dexamethasone levels as antiepileptic drugs enhance dex clearance
What happens after hypercortisolism is confirmed? Why?
Need to determine ACTH levels. High = ACTH dependent disease. Low = ACTH independent disease.
How does the Dexamethasone Challenge work?
Low dose (1 mg) overnight or 2 mg/d over 48 hrs, then measure cortisol. Lower than normal = axis working, rules out Cushing syndrome
3 caveats to the dexamethasone challenge
- Estrogens -> inc cortisol-binding globulin -> false-pos test. Need to stop for 6 weeks to do test 2. Antiepileptics and alcohol -> inc hepatic clearance. 3. Liver disease -> dec clearance.
Why might a high dose Dex test be done?
8 mg overnight test. Even pituitary ACTH secreting tumor will respond -> dec cortisol. High dose -> negative feedback on pituitary ACTH-producing cells, but not on ectopic ACTH-producing cells or adrenal adenoma.
What dex test results would be seen with Cushing Disease
Low: no dec in cortisol. High: suppresses cortisol.
What dex test results would be seen with ectopic cells secreting ACTH?
Low and High dose both yield no suppression of cortisol.
What dex test results would be seen with Cushing syndrome caused by an adrenal tumor?
Low ACTH. No response to low dose. High dose test usually not needed.
When would the CRF/H stimulation test be used?
Once Cushing syndrome is diagnosed to distinguish between Cushing disease (pituitary issue) and ectopic ACTH-secreting tumors.
What are the possible CRH stim test results and coordinating conditions?
Unresponsive: ectopic tumors and adrenal tumors. Responsive: pituitary tumors - CRF -> inc ACTH & cortisol.
How is ACTH measured in the CRF stimulation test?
Concurrent pituitary venous drainage and peripheral venous sampling of ACTH. 2.5x difference = Cushing’s of pituitary origin. Equal = ectopic tumor.
Effect of glucocorticoids on CV system
Pos inotropic effect, increased BP d/t Na & water reten
Effect of glucocorticoids on CNS
Lowers seizure threshold. Behavior changes e.g. mood dep or elevation, euphoria, restlessness. Anxiety and psychosis possible.
Effect of glucocorticoids on GI system
Increased gastric acid and pepsin, may suppress local immune response v h. pylori -> ulcer, decreased Ca abs from gut
Effect of glucocorticoids on bone metabolism
Direct inhib of osteoblasts w 2* stim of PTH -> stim osteoclasts. Net absorption of bone matrix.
Effect of glucocorticoids on skeletal muscle
Weakness, fatigue, muscle wasting d/t loss of protein, hypokalemia.
Hematological effect of glucocorticoids
Dec lymphocytes (T cells dec > B cells) -> susceptible to infection. Dec eosinophils & basophils. Increased neutrophils and erythrocytes. Inhibits leuocyte extravasation.
