Editor's Note: This article originally appeared in the Fall, 1998 issue of the Cushing's Support and Research Foundation (CSRF) newsletter and was updated in June, 2003. Dr. Hershel Raff, Ph.D. is a Professor of Medicine and Physiology at the Medical College of Wisconsin's Endocrine Research Laboratory at St. Luke's Medical Center in Milwaukee, Wisconsin.

Cushing's syndrome - endogenous hypercortisolism - is characterized by a loss of circadian rhythmicity. In normal patients, cortisol levels peak in the early morning hours and decrease to substantially lower levels at night. Rather than the normal decrease in late evening cortisol, patients with Cushing's syndrome of any cause fail to decrease cortisol secretion in the late evening. Therefore, the measurement of elevated late evening cortisol is helpful in the diagnosis of Cushing's syndrome. Obtaining a late night, unstressed plasma cortisol is virtually impossible in most clinical practices. Salivary cortisol is in equilibrium with the free, biologically active portion of cortisol in the plasma. Therefore, if one obtains a saliva sample in patients at bedtime in their homes under unstressed conditions, one can make the diagnosis of endogenous hypercortisolism.

A simple way to sample saliva is by using a Salivette made by the Sarstedt Company (Newton, NC). This device consists of a cotton tube and plastic tubes. The patient only has to chew the cotton tube for 2-3 minutes and place it inthe plastic tube. The tube is then mailed to our lab for analysis.

We currently recommend obtaining 2 salivary cortisol samples at 11 PM in any patient in whom Cushing's syndrome is suspected. If these are abnormal, the diagnosis can be confirmed using urine free cortisol or the low dose dexamethasone suppression test. Due to the convenience of sample collection, the patient can sample saliva several evenings in a row. In fact, our clinical endocrinologists routinely order 2-3 consecutive late-evening salivary cortisol samples. Our research (Raff H, Raff JL, Findling JW. 1998 Late-Night Salivary Cortisol as a Screening Test for Cushing's Syndrome. J Clin Endocrinol Metab. 83:2681-2686 and Raff H, Findling JW A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. 2003 Jun 17;138(12):980-91. Review) has shown that the combination of late-evening salivary cortisol and urine free cortisol is very accurate in diagnosing Cushing's syndrome in most patients. Doctors can obtain a kit by contacting ACL Client Services at 1-800-877-7016 or Salimetrics at 800-790-2258 . The analytical method used at ACL Labs and at Salimetrics is now FDA cleared for the diagnosis of Cushing's syndrome. Salivary cortisol analysis is also available from Esoterix and Quest Diagnostics.