July 14, 2016
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Elevated late-night salivary cortisol may indicate recurrent Cushing’s disease

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Elevated late-night salivary cortisol may serve as an early biochemical marker of recurrent Cushing’s disease, and prompt intervention may result in clinical benefits for people with Cushing’s disease, according to recent study findings.

According to the researchers, late-night salivary cortisol level is more sensitive for detecting Cushing’s disease recurrence compared with urinary free cortisol or a dexamethasone suppression test.

“Two important implications are that urine free cortisol should not be used as a screening tool for the detection of recurrent Cushing’s disease and that patients with Cushing’s disease should be screened with late-night salivary cortisol,” Ty B. Carroll, MD, assistant professor at the Medical College of Wisconsin Endocrinology Center and Clinics in Menomonee Falls, told Endocrine Today. “If the late-night salivary cortisol is abnormal therapy should be considered if the patient has clinical features that may be related to cortisol excess.”

Ty Carroll

Ty B. Carroll

Carroll and colleagues evaluated 15 patients (14 women; mean age, 49.1 years) with postsurgical recurrent Cushing’s disease (mean time to recurrence, 3.3 years) after initial remission to determine the performance of urinary free cortisol and late-night salivary cortisol measurements for detecting recurrent Cushing’s disease.

Participants were identified as having Cushing’s disease between 2008 and 2013; there was no standard for follow-up, but after remission confirmation participants were followed at least every 6 months after surgery for 2 years and then annually thereafter. Late-night salivary cortisol was the primary biochemical test to screen for recurrence, and follow-up tests with a dexamethasone suppression test, urinary free cortisol or other tests were performed if late-night salivary results were abnormal or if suspicion of recurrence was high.

Of the cohort, 80% had normal urinary free cortisol (< 45 µg/24 hours) at recurrence. Primary transphenoidal adenoma resection was performed in all participants. Evidence of pituitary adenoma on MRI at the time of recurrence was present in seven of 12 participants with normal urinary free cortisol and two of three participants with abnormal urinary free cortisol. Normal renal function was present in all participants, and 14 underwent testing with late-night salivary cortisol, dexamethasone suppression test and urinary free cortisol.

Of participants with normal urinary free cortisol at recurrence, nine had an abnormal dexamethasone suppression test (cortisol 1.8 µg/dL), and all had at least one elevated late-night salivary cortisol measurement (> 4.3 nmol/L). Mean late-night salivary cortisol was 10.2 nmol/L, and mean urinary free cortisol was 19.9 µg/24 hours.

Therapy for recurrent Cushing’s disease was administered in 11 of the 12 participants with abnormal urinary free cortisol. Adrenocorticotropic hormone (ACTH)-staining pituitary adenoma was confirmed in three participants who underwent repeat transphenoidal adenoma resection. Pharmacotherapy was administered to seven participants with normal urinary free cortisol, and two additional participants underwent bilateral adrenalectomy.

Abnormal dexamethasone suppression test was found in two participants with elevated urinary free cortisol at the time of recurrence, and two participants had confirmed abnormal late-night salivary cortisol. All three participants with elevated urinary free cortisol at the time of recurrence underwent therapy.

“This study highlights two separate but important issues,” Carroll told Endocrine Today. “The first has been described previously and here confirmed that urinary free cortisol is a very insensitive tool for the detection of recurrent Cushing’s disease. The second and more novel message is that patients with recurrent Cushing’s disease, as defined by elevations in late-night salivary cortisol, may have significant clinical benefit from treatment. This benefit occurs even in the absence of elevations of urine free cortisol.” – by Amber Cox

Disclosure: Carroll reports being a consultant for Corcept Therapeutics. Please see the full study for a list of all other authors’ relevant financial disclosures.