Late-Night Salivary Cortisol Cut-Offs for Diagnosis of Cushing Syndrome Using Second-Generation Electrochemiluminescence Immunoassay Kits

Abstract

Context: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second- generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population.

Objective: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits.

Design: Diagnostic accuracy study.

Methods: We prospectively recruited 155 controls aged 18–60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25–30 kg/m2 and hypertension and/or

diabetes [n = 52] or BMI = 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/ obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method.

Results: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs =6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and =7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively.

Conclusions: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff =6.73 nmol/L to diagnose CS.