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J Clin Endocrinol Metab. 2014 Jun;99(6):2045-51. doi: 10.1210/jc.2013-4262. Epub 2014 Mar 14.

Late-night salivary cortisol has a better performance than urinary free cortisol in the diagnosis of Cushing's syndrome.

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Division of Endocrinology Department of Medicine (P.C.L.E., B.F.C.B., L.M.M., M.C., A.C.M.) and Division of Statistics Department of Social Medicine (E.Z.M.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo 14049-900, Brazil.



The comparison of variability, reproducibility, and diagnostic performance of late-night salivary cortisol (LNSF) and urinary free cortisol (UFC) using concurrent and consecutive samples in Cushing's syndrome (CS) is lacking. Objectives, Patients, and Methods: In a prospective study, we evaluated 3 simultaneous and consecutive samples of LNSF by RIA and UFC by liquid chromatography associated with tandem mass spectrometry in Cushing's disease (CD) patients (n = 43), adrenal CS patients (n = 9), and obese subjects (n = 18) to compare their diagnostic performances. In CS patients, we also performed a modified CS severity index.


There was no difference in the coefficient of variation (percentage) between LNSF and UFC among the 3 samples obtained for each patient with Cushing's disease (35 ± 26 vs 31 ± 24), adrenal CS (28 ± 14 vs 22 ± 14), and obesity (39 ± 37 vs 48 ± 20). LNSF confirmed the diagnosis of hypercortisolism even in the presence of normal UFC in 17.3% of CS, whereas the inverse situation was not observed for UFC. The area under the receiver-operating characteristic curves for LNSF was 0.999 (95% credible interval [CI] 0.990-1.00) and for UFC was 0.928 (95% CI 0.809-0.987). The ratio between areas under the curve was 0.928 (95% CI 0.810-0.988), indicating better performance of LNSF than UFC in diagnosing CS. There was no association between the CS severity index and the degree of biochemical hypercortisolism.


Our data show that despite similar variability between both methods, LNSF has a superior diagnostic performance than UFC and should be used as the primary biochemical diagnostic test for CS diagnosis.

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