ESPE Abstracts

Background: Patients with congenital adrenal hyperplasia (CAH) might suffer from hyperandrogenism. For diagnosing and treatment monitoring, usually levels of androstenedione (A4) and testosterone (T) are measured in blood. More recently, adrenal-specific 11-oxygenated androgens such as 11- hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT) were introduced as promising biomarkers, but are not yet implemented for routine clinical care and reference intervals for children are lacking. We aim to quantify dehydroepiandrosterone (DHEA), A4, T, dihydrotestosterone (DHT), 11OHA4, 11KA4, 11OHT, and 11KT in healthy children to gain more insight into the natural course of these androgens. Moreover, we want to establish reference values for prepubertal and pubertal children to facilitate the interpretation of these androgen concentrations in CAH patients.

Methods: A sensitive two-dimensional liquid-chromatography tandem mass spectrometry assay was developed for the quantification of eight androgens (DHEA, A4, T, DHT, 11OHA4, 11KA4, 11OHT, and 11KT) and validated for clinical use. This included measurement of these androgens in a cohort of 256 healthy children (aged 0-17), which were divided into two groups based on age: a prepubertal cohort (n=133; 94 boys, 39 girls) with boys up to 10 and girls up to 9 years old, and a pubertal group (n=123; 52 boys, 71 girls) with boys over 11 and girls over 10 years old. In addition, the androgen concentrations of ten untreated paediatric CAH patients were measured and compared to the concordant reference cohort.

Results: We estimated age-adjusted median values for eightsteroids and computed reference intervals for the (11-oxygenated) androgens using a non-parametric (if n= ≥120) or transformed parametric (if n= <120) method (2.5 – 9.7 percentile). Concentrations of the 11-oxygenated androgens and DHEA started to rise around the age of 6 to 7 without sex differences. Untreated CAH patients have significantly higher concentrations of all androgens compared to the reference group.

Conclusions: The levels of adrenal-specific 11-oxygenated androgens show an age-dependent, but not sex-dependent, increase, which is most likely due to the onset of adrenarche. The 11-oxygenated androgens might be used as (additional) biomarkers to diagnose and monitor treatment of CAH patients, as conventional biomarkers show high variability. The reference intervals computed in this study facilitate the interpretation of (11-oxygenated) androgen measurements in these patients.