Question:  Depending on what you read, some sources think the 24 hour urine is the “gold standard” test for Cushing’s, while others think it’s the dexamethasone suppression test.  Some doctors will only start with a blood cortisol test, and a lot of resources I’ve read say that this is an almost worthless test.  How can Cushing’s patients feel confident when the literature and different doctors don’t agree on the best test for Cushing’s?  There are countless examples of people who had normal cortisol on their first test but did end up having Cushing’s.

Answer 1:  With regard to current laboratory testing, we all agree that it is imperfect in many cases, and can be misleading and very frustrating for the patient and the Physician as well. One test is not enough to send the patient on a course of therapy that may not work and may have side effects and/or complications. All of the treatments are designed to lower circulating cortisol levels, so unless we can be sure they are elevated, and that there is a good chance that they are the result of a pituitary source, it may not be wise to recommend treatment, especially surgery, before being certain.  It is well known that in some cases repeated testing may be needed to pin down the diagnosis with security.

By Dr. Edward Laws, Brigham and Women’s Hospital, Boston, MA

Answer 2:  Current guidelines recommend three tests for the diagnosis of possible Cushing syndrome: Late-night salivary cortisol, low-dose dexamethasone suppression test, and urine cortisol.  All 3 of these studies probe different aspects of abnormalities seen in patients who have either pituitary or adrenal Cushing syndrome.  Although urine cortisol was considered a “gold standard” in the 1980s and 1990s, it has become increasingly obvious to experienced clinicians that urine cortisol may lack adequate sensitivity in some patients.  In other words, some patients with pituitary and many patients with adrenal Cushing syndrome have normal urine free cortisol and a normal level should never be used to exclude the diagnosis.

Late-night salivary cortisol is the most sensitive means to detect patients with pituitary Cushing syndrome.  Virtually all patients who have pituitary Cushing syndrome will have elevations of late-night salivary cortisol – albeit sometimes intermittently.  Consistently normal late-night salivary cortisol levels exclude the diagnosis of pituitary Cushing syndrome.  Low-dose dexamethasone suppression test is always abnormal in patients with adrenal Cushing syndrome and abnormal in the vast majority of patients with pituitary Cushing syndrome.  Unfortunately, both late-night salivary cortisol and low-dose dexamethasone suppression testing have a 10-20% false positive rate and can be misleading. Therefore, abnormal results should ALWAYS be interpreted and evaluated by an endocrinologist.  However, normal levels of dexamethasone suppression testing and late-night salivary cortisol exclude Cushing syndrome of any type.  Consequently, many of us believe that these two studies should be the initial tests utilized in the screening of patients with possible Cushing syndrome.

By Dr. James Findling, Medical College of Wisconsin, Menomonee Falls, WI

(Summer 2018)