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), 11β-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). RESULTS: Similar to the previously described rhythmicity of 17OHP, 11OHA4 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 (11-OHA4: mean reduction of hormone concentrations between timepoint 1 and 5 (Δ (mean)) in male patients = 66%; male controls Δ (mean) = 83%; female patients Δ (mean) = 47%; female controls Δ (mean) = 86%; 11KT: male patients Δ (mean) = 57%; male controls Δ (mean) = 63%; female patients Δ (mean) = 50%; female controls Δ (mean) = 76%). Significant correlations between the area under the curve for 17OHP and 11KT (r(p)(male) = 0.773(<0.0001); r(p)(female) = 0.737(<0.0001)), and 11OHA4 (r(p)(male) = 0.633(0.0002); r(p)(female) = 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.