A New Diagnostic Test! Salivary Cortisol: A Screening Technique By: Dr. Hershel Raff

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 in the plastic tube. The tube is then transported to our lab for analysis.

Late-evening salivary cortisol is not intended to replace the current standard screening test - measurement of a 24 hr urine free cortisol. However, the salivary cortisol test can be extremely useful for patients suspected of having intermittent Cushing's syndrome. 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) 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.

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It is best to have an endocrinologist who is familiar with Cushing's. Unfortunately, many are not. The thyroid testing will not help with Cushing's diagnosis.

Of course, not every patient with Cushing's has all these tests, but some of the tests that help diagnose Cushing's are (click on any of the names for more information):

• BLOOD
  • 2-Hour Post-Prandial Plasma Glucose
  • Androstenedione
  • Blood Calcium (Ca+)
  • Calcium
  • Dexamethasone Suppression
  • Fasting Plasma Glucose
  • Insulin
  • Insulin Tolerance
  • Metyrapone
  • Plasma ACTH
  • Plasma Cortisol
  • Plasma Renin Activity
  • Total Carbon-Dioxide Content
• DEXAMETHOSONE TESTS
• PETROSAL SINUS SAMPLING (PSS) (for pituitary Cushing's)
• SALIVARY CORTISOL
• URINE TESTS
  • 17-Hydroxycorticosteroids (17-OHCS)
  • 17-Ketogenic Steroids (17-KGS)
  • 24 Hour Urine
  • Free Cortisol (UFC)
  • High Cortisol
  • Potassium

Directions for the Twenty-four Hour Urine Test Physicians have always relied upon analysis of urine specimens in order to diagnosis and treat many disease processes. Twenty-four hour urine collections are often employed to estimate the production rates of various hormones. The accuracy of test results depends entirely on the accuracy of the urine collection technique. These instructions are provided as a guide to ensure that your 24-hour urine collection is obtained in a manner that will permit reliance upon the test results.

You should collect every drop of your urine produced during a 24-hour period. You should begin the collection in the morning or else at a time specified by your physician. At that time, pass your urine, flush it down the toilet, and note the exact time. These measures permit you to start with an empty bladder and an empty collection bottle. Thereafter, collect every single drop of urine during the day and following night. The very next morning, exactly 24 hours from the start time, you should empty your bladder and add that urine to the collection bottle. This will complete the collection. There should be no more than a 5 or 10 minute variation between the start and stop time. If you find that you must urinate an hour or so before the appointed time, go ahead and do so, then drink a full glass of water so that you could urinate again at the time to end the collection.

Urine samples should be collected in a large cup or other container and then poured into the large bottle. Do not try to urinate directly into the bottle. Void urine prior to bowel movements in order to avoid losing urine that might normally be passed during a bowel movement.

Some patients are asked to collect more than one consecutive 24-hour urine sample. If that is the case, you should complete the first collection as instructed. Then, begin the second collection by adding any urine made in the next 24-hours to the second bottle. You should not discard any urine when starting the second or any subsequent collections. Simply change bottles at the stop and start times after adding that last sample required to complete the previous collection.

The bottles for some tests contain a weak acid as a preservative. Do not discard the acid. If you accidentally get acid or urine from the bottle on your skin or clothing, rinse the effected area immediately with plenty of cold water. Collection bottles must be refrigerated. This is best accomplished by using an ice chest, cooler, or if so inclined, your refrigerator.

If you forget to collect all of the urine or perform the test improperly, discard the specimen and start again on another day. If the bottle contained an acid preservative, you will need to obtain a new bottle from the laboratory or your physician's office. Otherwise, you may reuse the bottle after rinsing it with distilled water.

There are several types of Dexamethosone Suppression Tests, but all involve precise timing, both in thaking the dsxamethosone and in the blood draw. Some types of this test also incorporate urine collection. Please check with your endocrinologist to determine exactly what must be done, and at what time.