Diagnostic Utility of Diurnal Salivary Cortisol Profiles in Neoplastic and Non-Neoplastic Hypercortisolism

OBJECTIVE: Salivary cortisol has the advantages of being non-invasive, readily accessible in ambulatory patients and reflecting the free bioactive fraction of cortisol. The cortisol diurnal cycle, based on six samples collected every 4 hours over a 24-hour period, allows a detailed characterization of cortisol variations throughout the day. The objective of this study was to assess the value of the salivary cortisol diurnal cycle for the diagnosis of Cushing's syndrome (CS) and the differential diagnosis of non-neoplastic hypercortisolism. DESIGN: This retrospective cohort study included all the patients hospitalized in Endocrinology department of Cochin Hospital between 2012 and 2018 who had complete serum and salivary diurnal cycle assessments. METHODS: Serum and salivary cortisol levels were measured using an automated and a radio immunoassay, respectively. RESULTS: A total of 227 subjects without CS, 46 patients with non-neoplastic CS, 72 patients with ACTH-dependent CS and 67 with adrenal CS were included. For the diagnosis of CS, the cortisol nadir throughout the day showed better diagnostic performance than midnight cortisol, both in serum and saliva with, ROC AUCs of 0.98 and of 0.96, respectively. For the differential diagnosis between non-neoplastic hypercortisolism and ACTH-dependent CS, salivary cortisol showed better diagnostic performance than midnight serum cortisol (ROC AUC 0.97; optimal cut-off 5.3 nM; sensitivity 90%; specificity 87% for the salivary cortisol nadir). CONCLUSION: The salivary cortisol diurnal cycle appears to be a powerful tool for the diagnosis of CS and for the challenging differential diagnosis of non-neoplastic hypercortisolism, with the major advantage of being accessible in ambulatory patients.