Question: I have symptoms of Cushing’s but my 24-hour urinary cortisol measurement is normal. Is it possible to have a normal test and still have Cushing’s?

Answer: The 24h urine free cortisol test is an extremely sensitive and specific test for the presence of Cushing’s. When the level is high, it is likely that the patient has Cushing’s. There are a few other conditions that can cause high cortisol, including depression and alcoholism. When a 24h urine free cortisol is normal, the chance of the patient having Cushing’s syndrome is less than 1%. This generally occurs only in: 1) a very early stage of Cushing’s before the urine cortisol is consistently high, or 2) a rare condition called “periodic hormonogenesis” or cyclic Cushing’s, in which a patient has periodic excess secretion of cortisol, but is normal between these episodes. These conditions are best diagnosed by having the patient collect multiple samples over time. In the vast majority of patients, however, a normal 24h urine free cortisol excludes the diagnosis of Cushing’s.

By Dr. Beverly MK Biller, MD (Spring 1995)