Testing for adrenal insufficiency: random cortisol level versus cort stim test

Let’s say a patient presents to the medical floor with hypotension and hyperkalemia, and generalized fatigue and weakness. Adrenal insufficiency might be on your differential. What’s the most accurate way to test for it? Can you get away with using doing a random cortisol level?

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Reference

A random serum cortisol level must always be in the context of what time of day it was taken. There are different laboratory cutoffs depending on what time of day the sample was taken. Typically, a morning cortisol level is most helpful. An AM cortisol level >15 mcg/dL is very reassuring that someone doesn’t have adrenal insufficiency. But any level <15 does not exclude adrenal insufficiency! As this case report shows.

A cort stim test (also called ACTH/cosyntropin stim test) involves measuring an AM serum cortisol, injecting 250 mcg of ACTH or cosyntropin, waiting 30 minutes, and then measuring serum cortisol again. An “adequate response” ruling out adrenal insufficiency is  ≥18 to 20 mcg/dL before or after ACTH injection. If there is an inadequate response, you may consider directly measuring ACTH levels or doing other tests to further evaluate for primary vs. secondary adrenal insufficiency.

Note 1: patients with higher levels of cortisol-binding globulin (like cirrhotics or those with nephrotic syndrome) may have lower levels of cortisol, and may be incorrectly diagnosed with adrenal insufficiency using normal cut-off ranges.

Note 2: this doesn’t apply to patients who are really, really sick in the ICU. As this review discusses, critically ill patients are probably relatively adrenally insufficient because they need tons of cortisol to maintain perfusion and create an inflammatory response.

One point that this review makes is:

Our belief is that adrenal insufficiency appears to be unlikely when a random cortisol measurement is greater than 34 μg per deciliter. Conversely, adrenal insufficiency is likely if the serum cortisol level is below 15 μg per deciliter during acute severe illness. For persons with cortisol levels between these two values, a poor response on a corticotropin test would indicate the possibility of adrenal insufficiency and a need for supplemental corticosteroids.

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