CONTEXT Although salivary steroid sampling offers several advantages, the diagnostic potential of salivary steroid metabolites remains largely unexplored.

OBJECTIVE This work aimed to evaluate the diagnostic utility of salivary steroid profiling in patients with adrenal diseases.

METHODS This prospective, multicenter study comprised 313 patients with nonfunctioning adrenal adenoma (NF), primary aldosteronism (PA), Cushing syndrome (CS), and mild autonomous cortisol secretion (MACS). Salivary samples for morning and night steroids were collected using standardized protocols. The liquid chromatography-mass spectrometry-based steroid profiling was applied to quantify cortisol, cortisone, tetrahydrocortisone (THE), 20α-dihydrocortisol (20α-DHF), 18-hydroxycortisol (18-OHF), and dehydroepiandrosterone sulfate (DHEA-S). The primary outcome was the diagnostic performance of morning and night salivary steroids.

RESULTS In the PA group, morning and night salivary levels of 18-OHF were higher compared to the other groups (all P < .05). Morning and night salivary levels of cortisone, THE, and 20α-DHF were significantly elevated in the CS group compared to other groups (all P < .05). Only night-time salivary levels of cortisone (P = .040) and 20α-DHF (P = .029) were elevated in the MACS group compared to the NF group. Receiver operating characteristic analyses indicated that morning salivary 18-OHF was moderately specific for PA, whereas night salivary 20α-DHF and cortisone provided robust diagnostic accuracy for CS. Combined night salivary steroids exhibited superior diagnostic performance compared to morning salivary steroids in the CS group (area under the curve, 0.903 vs 0.754; P = .007).

CONCLUSION Salivary steroid profiling holds promise as a noninvasive tool for the diagnosis of adrenal diseases.