Rose: Adrenal Pharmacology Flashcards
(42 cards)
What is an ACTH stimulation test? What does it tell you?
Compares blood cortisol levels before and after 250 micrograms of tetracosactide (synthetic ACTH) (IV) is given.
If cortisol exceeds normal levels (↑ by at least 2x) by 1 hour, then primary adrenal gland fxn = normal
When do you do a long ACTH Stimulation test?
if short test reveals that cortisol is abnormal
used to differentiate between primary and secondary adrenal insufficiency
How do you do a long ACTH stimulation test? What does it tell you?
1 mg tetracosactide (IV/IM) multiple administrations → blood taken 1, 4, 5, and 24 hrs later
How does a LONG ACTH stimulation test allow you to differentiate between primary and secondary adrenal insufficiency?
o In 1- Addison’s Dz → cortisol level is ↓ at all time points
o In 2- corticoadrenal insufficiency (adrenal gland is small but still responsive) → delayed but normal response of ↑ cortisol is seen
What are the 5 steps to establish hypercortisolism and determine the origin of Cushing syndrome?
- 24 hr urine sample measurement of FREE cortisol
- Late night salivary cortisol (>2 tests)
- Special populations (prego and epilepsy)
- Once hypercorisolism is established a baseline plasma ACTH is obtained
- Dexamethosone challenge test
High levels of cortisol in a 24 hr urine sample indicate….
Hypercorisolism (overwhelms metabolism conversion to inactive cortisone)
Late night salivary cortisol tests that show a LOSS of circadian rhythm and ABSENCE of late night nadir are indicative of…
CUshings syndrome
What should you not use to test a pregnant women that you suspect may have hypercortisolism?
Urine sample–urine tends to be FREE of cortisol
What test should not be used in epileptics in that you suspect have hypercortisolism?
dex text (antiepileptic drugs ENHANCE dex clearance)
Use urine or salivary cortisol
Once hypercortisolism is established a baseline ACTH is obtained. What is hte difference between a high and low level?
LOW ACTH> ACTH indep disease
HIGH ACTH> ACTH dep disease
What is the gold standard screening test for hypercortisolism?
A. Low Dose Dex Test: 1 mg dexamethasone test overnight or 48 h 2 mg/d dexamethasone test
How do you interpret a low dose dex test?
o If blood levels of cortisol are lower than normal (post-test) → Cushing Syndrome can be ruled out
o If blood levels of cortisol are NOT lower than normal (post-test) → fail test
How does estrogen affect dex drug clearance?
Estrogen ↑ the cortisol-binding globulin (CBG)
→ result in false positive rates with dex test
(estrogen containing drugs like OCPs should be stopped 6 weeks before test)
How do antiepileptics affect dex drug clearance?
(phenytoin, carbamazepine, and EtOH)
→ induce hepatic enzymatic clearance of dexamethasone
How does liver disease affect dex drug clearance?
DECREASES clearance of dex
What test is used to distinguish Cushing pituitary ACTH secreting tumor from ectopic cells?
High Dose Dex Text
pituitary ACTH secreting tumor will show ↓ to dexamethasone in cortisol
What will Cushing syndrome caused by an adrenal tumor show on a dex test?
- Low dose test: no change
- ACTH level: low
In most cases, the high dose test is not needed
What will Dex tests show in a pt with Cushing Syndrome related to ectopic ACTH producing tumor?
Low dose test: no change
ACTH level: high
High-dose test: no change
What will dex tests show in a pt with CS cuased by a pituitary tumor (Cushing disease)?
Low dose test: no change
High dose test: normal suppression (if there is no suppression → another test is needed)
How do glucocorticoids affect the CVS?
- Positive inotropic effect (↑ strength of muscular contraction)
- Na+/H2O retention → ↑ BP
- Maintains the sensitivity of small vessels to catecholamines → retains tone and BP
How do glucocorticoids affect the CNS?
- ↓ seizure threshold
* Behavioral Δs: mood depression/elevation (common), euphoria and restlessness (some), anxiety and psychosis (possible)
How do glucocorticoids affect the GI System?
- ↑ gastric acid and pepsin
- may suppress the local immune response against H. pylori → ulcer formation
- ↓ Ca++ absorption from the gut
How do glucocorticoids affect bone metabolism?
- direct inhibition of osteoblasts
- 2o stimulation of parathyroid hormone → stimulates osteoclasts
- Net absorption of bone matrix
How do glucocorticoids cause skeletal muscle wekaness and fatigue?
- Hypokalemia
- Muscle wasting – loss of protein
- May result in a greater disability than the original inflammation