Salivary Profiles of 11-oxygenated Androgens Follow a Diurnal Rhythm in Patients With Congenital Adrenal Hyperplasia

Context: Several studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD). Objective: To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD. Design, Setting, and Participants: Cross-sectional single-center study including 59 patients with classic 21OHD (men=30; women=29) and 49 body mass index- and age-matched controls (men=19; women=30). Outcome Measures: Salivary concentrations of the following steroids were analyzed by liquid chromatography-tandem mass spectrometry: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11 beta-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). Results: Similar to the previously described rhythmicity of 17OHP, 11-OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11OHA4: mean reduction of hormone concentrations between timepoint 1 and 5 (Delta(mean)) in male patients=66%; male controls Delta(mean)=83%; female patients Delta(mean)=47%; female controls Delta(mean)=86%; 11KT: male patients Delta(mean)=57%; male controls Delta(mean)=63%; female patients Delta(mean)=50%; female controls Delta(mean)=76%). Significant correlations between the area under the curve for 17OHP and 11KT (r(male)(p)=0.773(<0.0001); r(female)(p)=0.737(<0.0001)), and 11OHA4 (r(male)(p)=0.633(0.0002); r(female)(p)=0.564(0.0014)) were observed in patients but not present or reduced in controls. Conclusions: Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.