Salivary profiles of 11-oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia.

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Several studies have highlighted the importance of the 11oxygenated 19carbon (11oxC19) adrenalderived steroids as potential biomarkers for monitoring patients with 21hydroxylase deficiency (21OHD).To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.Cross-sectional single center study including 59 patients with classic 21OHD (men=30; women=29) and 49 BMI- and agematched controls (men=19; women=30).Salivary concentrations of the following steroids were analyzed by LCMS/MS: 17hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11βhydroxyandrostenedione (11OHA4) and 11ketotestosterone (11KT).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 one and five (Δmean) in male patients = 66 %; male controls Δmean = 83 %; female patients Δmean = 47 %; female controls Δmean = 86 %; 11KT: male patients Δmean = 57 %; male controls Δmean = 63 %; female patients Δmean = 50 %; female controls Δmean = 76 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r pmale = 0.773 <0.0001; r pfemale = 0.737 <0.0001), and 11OHA4 (r pmale = 0.633 0.0002; r pfemale = 0.564 0.0014) were observed in patients but not present or reduced in controls.Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.

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Authors: Hanna Franziska Nowotny, Matthias K Auer, Christian Lottspeich, Heinrich Schmidt, Ilja Dubinski, Martin Bidlingmaier, Jo Adaway, James Hawley, Brian Keevil, Nicole Reisch