Practical Testing Methods for High Cortisol Levels

GLP-1 medications might be most well-known as weight-loss options, but they were originally developed as a treatment for type 2 diabetes. For many patients, the drugs remain a highly effective treatment for the condition.

However, GLP-1s are not perfect and don’t work for every patient. In April of this year, Pharmaceutical Executive spoke with Mark Bagnall, CEO of Phenomix, discussed various reasons why a significant number of patients go off the medication within the first year of using it. His discussion focused on how side effects can be severe and incapitating, while the results can be inconsistent.

Pharmaceutical Executive recently spoke with Dr. Elena Christofides, scientific/medical advisor for Sparrow Pharmaceuticals, about a different issue some GLP-1 users face. Specifically, patients with high cortisol levels face unique challenges that GLP-1s may not be able to tackle.

Pharmaceutical Executive: What are practical testing options for identifying elevated cortisol?
Dr. Elena Christofides: There are numerous ways to test for cortisol, but it is worth being clear about which tests are and are not appropriate. The least effective approach — and one that should never be used for this purpose — is a random cortisol and ACTH value. For reasons I can't fully explain, this still persists in clinical practice, perhaps because we routinely use random testing for other hormones. But the cortisol system cannot be assessed that way. It is too episodic.

The tests that were designed to evaluate cortisol have important limitations worth understanding. The 24-hour urine free cortisol was developed over 50 years ago specifically to identify pituitary disease, which means it has limited utility in adrenal disease. The salivary cortisol test was developed in the 1990s to detect recurrent pituitary disease in patients who had already undergone surgery — making it highly sensitive, but not well-suited for population screening. It can flag people with circadian disruption who don't actually have disease, which significantly limits its specificity.

The only true dynamic test of the HPA axis is the overnight dexamethasone suppression test, or ODST. This test was designed specifically to assess the responsiveness of the cortisol system — because a healthy HPA axis should respond to external steroids. When you administer dexamethasone, you should be able to suppress endogenous cortisol production. That is the hallmark of a functioning system. If you cannot suppress endogenous cortisol with exogenous steroids, you have identified a priori a dysfunctional HPA axis.

Realistically, the ODST is the only test that matters for screening purposes — the only one that tells you whether you are dealing with an HPA axis problem in the first place.