Hershel Raff, Ph.D., Medical College of Wisconsin and St. Luke’s Medical Center, Milwaukee, WI
Cortisol is produced by the adrenal glands and is an important hormone for normal health. Normally, cortisol is secreted with a distinctive daily pattern called a "circadian rhythm" - cortisol levels peak in the morning (usually between 7 and 8 AM) and decrease to substantially lower levels late at night. Cushing's syndrome is characterized by excessive cortisol production. The most common cause is an ACTH-secreting pituitary tumor. Since ACTH is the natural stimulator of cortisol production, too much ACTH causes the adrenal glands to grow (adrenal hyperplasia) and produce too much cortisol. (There are other causes of Cushing's syndrome in addition to pituitary tumors.)
One of the hallmarks of Cushing's syndrome of any cause is a loss of circadian rhythmicity. 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 a very simple and useful way to screen patients for Cushing's syndrome. Obtaining a late night, unstressed blood cortisol level is virtually impossible in most clinical practices. Salivary cortisol is an accurate reflection of the free, biologically active portion of cortisol in the blood. Therefore, by obtaining 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 cotton tube and a plastic tube. The patient only has to chew the cotton tube for 2-3 minutes and place it in the plastic tube. The tube is then transported to a laboratory for analysis. An alternate method is to collect saliva by expectorating directly into a test tube.
Late-evening salivary cortisol is not intended to replace the current standard screening test, but rather, complements the measurement of a 24 hr urine free cortisol. In addition to screening for Cushing's syndrome of any type, the salivary cortisol test can be extremely useful in the evaluation of patients suspected of having intermittent (waxing and waning) Cushing's syndrome. Due to the convenience of sample collection, the patient can sample saliva several evenings in a row.
There are other potential uses for salivary cortisol measurement. One is to assess decreased cortisol production (adrenal insufficiency) in patients with kidney failure or in whom blood drawing is difficult or inconvenient. The adrenal glands still need to be stimulated with synthetic ACTH (cosyntropin), with measurement of salivary cortisol substituted for blood cortisol. Salivary cortisol is also being used to search for patients with food-induced cortisol secretion, a recently discovered variation on the Cushing's syndrome theme.
There may be other uses developed in the future for salivary cortisol, and possibly other hormones measured in saliva. Testing saliva for other hormones has not been studied adequately to be used for clinical diagnosis and therapy at the current time. In the future, this may be possible.
