SUN-475 Circadian Salivary Cortisol And Cortisone Concentrations In Patients With Endogenous Hypercortisolism: A Cross-sectional Study

Abstract Disclosure: S. Ahmadian: None. S.R. Chacko: None. S. Sharma Sharma: None. V.M. Fell: None. A. Peersen: None. E.J. Atkinson: None. K.L. Moehnke: None. Y. Chai: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Cortisol secretion follows a circadian pattern with highest concentrations in the morning, and lowest at night. Loss of circadian cortisol variation has been reported in patients with Cushing syndrome (CS), however, is scarcely investigated in patients with mild autonomous cortisol secretion (MACS). Outpatient assessment of late night and early morning salivary cortisol and cortisone may serve as a valuable diagnostic tool in patients with hypercortisolism. Methods: We conducted a single-center cross-sectional study of adults evaluated at our center between 04/2024 and 04/2025. The study included patients with Cushing’s syndrome (CS), mild autonomous cortisol secretion (MACS), and referent subjects without known adrenal disorders. Participants were provided with two cotton swabs (Salivettes) and instructed to collect saliva samples at two standardized time points: at bedtime (PM) and on waking (AM). Each swab was kept in the mouth for 2-2.5 minutes. Saliva was analyzed for cortisol and cortisone using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Delta cortisol and delta cortisone were defined as the difference between AM and PM concentrations for each individual and were calculated for all participants. Results: A total of 82 patients (32 with ACTH-dependent CS, 5 with ACTH-independent CS, and 45 with MACS), median age of 55 years [IQR 44-65], 63 (77%) women, and 71 referent subjects, median age of 34 years [IQR 28-42], 54 (76%) women, were included. Delta cortisol was higher in referents (median of 212 ng/dL, [IQR 157-358]) vs patients with CS (median 95 ng/dL [IQR -21-184]) or MACS (median 131 ng/dL, [IQR 91-229]). Similarly, delta cortisone was also highest in referents with a median of 828 ng/dL [IQR 612-1131] versus median of 211 ng/dL [IQR -58-468] in CS and 484 ng/dL [IQR 189-849] in MACS. When compared to referents in an age- and sex-adjusted linear regression model, delta cortisone was lower in both patients with CS (est -1.3 (95%CI -1.75 to -0.85), P<0.001 and MACS (est -0.66, 95%CI of -1.17 to -0.16, P=0.010). Delta cortisol was lower in patients with CS (est -1.32, 95%CI -2.11 to -0.54, P=0.001), but not MACS (est -0.51, 95%CI -1.39 to 0.36). Conclusion: Patients with both CS and MACS demonstrate a blunted circadian salivary cortisol and cortisone secretion, as reflected by a lower delta cortisol and cortisone when compared to referent subjects. Assessment with delta salivary cortisone in patients with MACS may be more valuable than a standard of care late night salivary cortisol assessment. Presentation: Sunday, July 13, 2025