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Nowotny, Hanna Franziska; Auer, Matthias K.; Lottspeich, Christian; Schmidt, Heinrich; Dubinski, Ilja; Bidlingmaier, Martin; Adaway, Jo; Hawley, James; Keevil, Brian und Reisch, Nicole (2021): Salivary Profiles of 11-oxygenated Androgens Follow a Diurnal Rhythm in Patients With Congenital Adrenal Hyperplasia. In: Journal of Clinical Endocrinology & Metabolism, Bd. 106, Nr. 11, E4509-E4519

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Abstract

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.

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