Introduction: Glucocorticoid treatment remains a challenging aspect in the management of congenital adrenal hyperplasia (CAH). Current strategies for monitoring treatment are suboptimal and rely largely on frequent blood tests, which are traumatising in children and young persons (CYP). Recent evidence indicates a crucial role of 11-oxygenatedC19 androgens in the pathogenesis of CAH.
Aim: To explore the use of 11-oxygenatedC19 androgens in non-invasive clinical tests to monitor glucocorticoid treatment in CAH.
Objective: To establish the correlation between plasma and salivary androgens in CYP with CAH.
Patients and Methods: We conducted a prospective multi-centre study recruiting CYP with CAH across the United Kingdom. Participants included 78 patients (43 females, 35 males, 8-18 years (12.87+/-3.04 years)) and 62 matched controls. Using liquid chromatography tandem mass spectrometry, we measured plasma and salivary concentrations for five steroid hormones: 17-hydroxyprogesterone, androstenedione, testosterone, 11-hydroxyandrostenedione and 11-ketotestosterone. The relationship between plasma and salivary steroids was analysed by Spearman correlation to assess their usefulness in clinical practice.
Results: Salivary and plasma concentrations correlated well for all the five steroids measured, with the strongest correlations found for androstenedione and 11-ketotestosterone: androstenedione(rs=0.931, P<0.001), testosterone (rs=0.867, P<0.001), 17-hydroxyprogesterone(rs=0.871, P<0.001), 11-hydroxyandrostenedione(rs=0.876, P<0.001), 11-ketotestosterone (rs=0.944, P<0.001). In addition, high correlations were found in CYP with CAH when analysing subgroups based on gender and age. Plasma and salivary steroid concentrations were significantly raised in patients compared to controls for all hormones, with the exception of testosterone which was higher in healthy individuals compared to CAH patients for the subgroup of pubertal boys. Analysing patients subgroups of CAH control based on 17-hydroxyprogesterone concentrations (<15 nmol/L; 15-30 nmol/L; >30 nmol/L), the strongest correlations between plasma and saliva were found for androstenedione and 11-ketotestosterone in both overtreated (androstenedione(rs=0.797, P=0.002), 11-ketotestosterone (rs=0.888, P<0.001)) and undertreated(androstenedione(rs=0.924, P<0.001), 11-ketotestosterone (rs=0.878, P<0.001)) CAH patients.
Conclusions: We have established that salivary concentrations correlate well with plasma concentrations for androgens used as markers of therapy control in CAH patients. Importantly, the best correlations were found for adrenal-derived 11-oxygenatedC19 androgen 11-ketotestosterone as well as 17-hydroxyprogesterone and androstenedione, which are widely used for CAH monitoring. Thus, we believe that this novel and improved combination of salivary steroid hormones can serve as non-invasive monitoring tool in CAH providing a significant amount of additional information and will ultimately improve management and outcomes in CAH.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology