The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism

Objective: The use of late-night salivary cortisol (LNSaIC) for diagnosing subclinical hypercortisolism (SH) is debated. No data are available regarding the role of LNSaIC as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in SH diagnosis. The aim of this study was to evaluate the diagnostic accuracy of LNSaIC measured by LC-MS/MS in SH. Design: Cross-sectional prospective study of outpatients. Methods: In 70 consecutive patients with adrenal incidentalomas (AI), without signs and symptoms of hypercortisolism, we diagnosed SH in the presence of at least two of the following: cortisol after 1 mg overnight dexamethasone suppression test (1 mg DST) > 83 nmol/l, 24-h urinary free cortisol (UFC) > 193 nmol/24 h, and morning ACTH < 2.2 pmol/l. The LNSaIC levels by LC-MS/MS at 2300 h (normal values < 2.8 nmol/l) and the presence of hypertension, type 2 diabetes mellitus (T2DM), and osteoporosis (OP) were assessed. Results: The increased LNSaIC levels (> 2.8 nmol/l) had an 83.3% specificity (SP) and a 31.3% sensitivity (SN) for predicting the biochemical diagnosis of SH. The increased LNSaIC had an 85.2% SP and a 55.6% SN for predicting the presence of hypertension, T2DM, and OP, while the combination of LNSaIC > 1.4 nmol/l (cutoff with 100% SN) plus 1 mg DST > 50 nmol/l had an 88.9% SN and an 85.2% SP (similar to SH criterion at enrollment). Conclusions: In AI patients, LNSaIC measured by LC-MS/MS appears to be useful in combination with 1 mg DST for diagnosing SH, while it is not useful as a single criterion.