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 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age-matched controls (men=15; women=17). Outcome Measures Salivary concentrations of the following steroids were analyzed by LC-MS/MS: 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: male patients Δ mean = 79 %; male controls Δ mean = 81%; female patients Δ mean = 33 %; female controls Δ mean = 91 %; 11KT: male patients Δ mean = 64 %; male controls Δ mean = 60 %; female patients Δ mean = 49 %; female controls Δ mean = 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p) male = 0.741**; r(p) female = 0.842****), and 11OHA4 (r(p) male = 0.385 n.s. ; r(p) female = 0.527*) were observed in patients but not in controls. Conclusions Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.