How do we diagnose Cushing's? We have 3 screening tests:
1. 24-hour Urinary Free cortisol 2. dexamethasone suppression test 3. Late night salivary cortisol
Late night salivary cortisol is THE BEST first test for Cushing's. Let's explore why the other two have their problems:
When can't we trust the dexamethasone suppression test?
1⃣.changes in Cortisol Binding Globulin (CBG)
⏫ CBG- increased estrogen (pregnancy, oral contraceptives, hormone replacement therapy), SERM
⏬ CBG- cirrhosis, nephrotic syndrome, critical illness
When can't we trust the dex suppression test?
2⃣ changes to dex metabolism
⏫ dex metabolism (CYP3A4 inducer)- anti seizure meds, pioglitazone, alcohol
⏬ dex metabolism- antidepressants (fluoxetine), diltiazem, cimetidine
ALWAYS measure a morning dex level with the cortisol!
How about 24 hour urine free cortisol?
Since we are measuring free cortisol, not total, changes to Cortisol Binding Globulin does not matter (like in the dex suppression test)
When can we not trust the 24-hr urine free cortisol?
1⃣Incorrect collection-even with the best instructions, patient may not collect urine adequately. Given variation in cortisol secretion by circadian rhythm, this leads to inaccuracy.
Solution? Get at least two 24hr collections
When can we not trust the 24-hr urine free cortisol?
2⃣exogenous steroids- steroids are in creams, supplements, inhalants, injections that will interfere with this test. Take a careful history to exclude these.
When can we not trust the 24-hr urine free cortisol?
3⃣High urine output- Volume >3L/day should be interpreted with caution
4⃣Renal impairment- GFR<60 can lead to false results
5⃣ Pregnancy- normal values can be several fold higher
For more info see this article as part of a beautifully crafted Cushing's-themed issue in Pituitary: link.springer.com/article/10.100…