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Clin Endocrinol (Oxf). 2012 Apr;76(4):467-72. doi: 10.1111/j.1365-2265.2011.04239.x.

Late-night salivary cortisol for diagnosis of Cushing's syndrome by liquid chromatography/tandem mass spectrometry assay.

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Division of Endocrinology, Metabolism and Nutrition, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.



Late-night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing's syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut-points.


The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis.


Late-night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver-operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut-off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%.


Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges.

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