THU207 11-oxygenated Androgens Are Strongly Associated With Treatment Quality In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency

Disclosure: O. Abawi: None. T. Du Toit: None. G. Sommer: None. C.D. Vögel: None. M. Groessl: None. U. Halbsguth: None. S.E. Hannema: None. C. de Bruin: None. E. Charmandari: None. E.L. van den Akker: None. C.E. Flueck: None. Introduction: Treatment of children with Congenital Adrenal Hyperplasia (CAH) aims at balancing steroid replacement, hyperandrogenism and hypercortisolism. Optimal treatment and its assessment however remain a conundrum. Currently, specialists integrate clinical and conventional laboratory parameters such as 17-hydroxyprogesterone (17OHP) and androstenedione (A4). In recent years, 11-oxygenated androgens (11oxyAs) have been proposed as promising biomarkers, but their merit in treatment monitoring is not yet established. Aim: To investigate potential biomarkers of treatment quality in children with CAH by comprehensive serum steroid profiling. Methods: This prospective, observational cohort study was conducted at 4 academic pediatric endocrinology outpatient clinics and included children with genetically confirmed 21-hydroxylase deficiency. At 2 consecutive visits (mean 4.1 ± 0.7 months apart), a targeted and untargeted panel of conventional adrenal and additional peripheral steroids was analysed in serum using liquid chromatography-mass spectrometry. This included 11β-hydroxy (11OH)-androstenedione (11OHA4), 11keto-A4 (11KA4), 11OH-testosterone (11OHT), and 11keto-T (11KT). At each visit, the pediatric endocrinologist classified patients as undertreated, optimally treated or overtreated based on detailed clinical and endocrinologic evaluation, including serum 17OHP and A4 profiling. Mixed-effects logistic regression analyses on log-steroid concentrations adjusted for age, sex, BMI-z, pubertal status, CAH subtype (classic vs non-classic) and random effects for unique patients were performed to investigate odds ratios (OR) of being undertreated vs optimally treated. False discovery rate adjusted P<0.05 was considered significant. Results: We included 138 visits (86 [62%] optimal treatment, 52 [38%] undertreatment) from 72 patients, of whom 31 (43%) girls, 59 (82%) had classic CAH, and 31 (43%) were prepubertal. Mean age at first visit was 10.6 ± 5.2 years, mean BMI-z was 0.6 ± 1.1. Ten out of 17 conventional steroids, including 17OHP and 21-deoxycortisol but not A4, were associated with undertreatment. All 11oxyAs were associated with undertreatment: 11OHA4 (OR 3.64, SE 1.42, P=0.008), 11OHT (OR 2.91, SE 1.09, P=0.012), 11KT (OR 2.77, SE 1.00, P=0.01), and 11KA4 (OR 2.64, SE 0.84, P=0.009). The strongest association with undertreatment was found for the sum of 11oxyAs (OR 4.04, SE 1.70, P=0.008). Discussion: We show that 11oxyAs have the strongest association with undertreatment in children with CAH. This study supports the inclusion of 11oxyAs in the biochemical work-up of CAH to improve treatment monitoring and underscores the importance of analysing unconventional steroids in CAH by comprehensive steroid profiling. Following on, our steroid profiling can now be extended to characterise other forms of CAH and cases of suspected overtreatment. Presentation: Thursday, June 15, 2023