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Radioimmunoassay and Tandem Mass Spectrometry Measurement of Bedtime Salivary Cortisol Levels: A Comparison of Assays to Establish Hypercortisolism

Reproductive Biology and Medicine Branch (S.K.B., M.W., L.K.N.), National Institute of Child Health and Human Development, and Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; and the George Washington University Weight Management Program (D.R.), Washington, D.C., 20037

Address all correspondence and requests for reprints to: Lynnette Nieman, M.D., Building 10, CRC, 1 East, Room 1-3140, 10 Center Drive, MSC 1109, Bethesda, Maryland 20892-1109. E-mail: NiemanL{at}nih.gov.

Context: Although bedtime salivary cortisol measurement has been proposed as the optimal screening test for the diagnosis of Cushing’s syndrome, its performance using commercially available assays has not been widely evaluated.

Objective: Our objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement of salivary cortisol in obese subjects and healthy volunteers.

Design and Setting: We conducted a cross-sectional prospective study of outpatients.

Subjects and Methods: We studied 261 obese subjects (186 female) with at least two additional features of Cushing’s syndrome and 60 healthy volunteers (30 female). Subjects provided split bedtime salivary samples for cortisol measurement by commercially available RIA and LC-MS/MS. Results were considered normal or abnormal based on the laboratory reference range. Subjects with abnormal results underwent evaluation for Cushing’s syndrome.

Results: In paired samples, RIA gave a lower specificity than LC-MS/MS in obese subjects (86 vs. 94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects with at least one abnormal result, both values were abnormal in 44% (confidence interval 26–62%) of obese and 75% (confidence interval 33–96%) of healthy volunteers. In obese subjects, salivary cortisol concentrations were less than 4.0 to 643 ng/dl (<0.11–17.7 nmol/liter; normal, 100 ng/dl, 2.80 nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4–77.3 nmol/liter; normal, 170 ng/dl, 4.7 nmol/liter) by RIA. Cushing’s syndrome was not diagnosed in any subject.

Conclusion: Salivary cortisol levels should not be used as the sole test to diagnose Cushing’s syndrome if laboratory-provided reference ranges are used for diagnostic interpretation.

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