Serum 11-ketotestosterone is associated with overall disease-control status but adds limited information beyond androstenedione in children with 21-hydroxylase deficiency.

INTRODUCTION: Monitoring children with 21-hydroxylase deficiency (21-OHD) requires suppression of adrenal androgen excess while avoiding glucocorticoid overtreatment. However, the clinical value of serum 11-oxygenated androgens beyond established biomarkers remains uncertain. We evaluated whether serum 11-ketotestosterone (11KT) is associated with overall disease-control status and whether it provides incremental information beyond androstenedione (A4). METHODS: We conducted a retrospective, single-center study of 67 children with classic 21-OHD and 67 healthy controls. Steroids were measured by liquid chromatography-tandem mass spectrometry in fasting serum samples collected at 08:00 before medication. Two pediatric endocrinologists, masked to all steroid results, independently adjudicated overall disease-control status using clinical information from the preceding 12 months. Associations of 11KT with disease status and A4 were examined after adjustment for relevant covariates. Discrimination was assessed using receiver operating characteristic analysis, and the incremental value of 11KT beyond age, sex, Tanner group, and A4 was evaluated using bootstrap-corrected ridge regression models. RESULTS: Serum 11KT was higher in children with 21-OHD than in healthy controls (adjusted geometric mean ratio, 1.81; 95% CI, 1.24-2.64; P = 0.002) and in suboptimally controlled than in well-controlled children (6.17; 95% CI, 3.18-11.97; P < 0.001). Within the 21-OHD group, 11KT was strongly correlated with A4 after adjustment for age, sex, and Tanner group (partial r = 0.843). The single-marker area under the receiver operating characteristic curve (AUC) was 0.875 for 11KT and 0.906 for A4. Adding 11KT to a ridge model containing age, sex, Tanner group, and A4 changed the bootstrap-corrected AUC from 0.912 to 0.903 and the corrected calibration slope from 0.835 to 0.695. Lower-limit sensitivity analyses yielded the same qualitative findings. DISCUSSION: Serum 11KT was associated with physician-adjudicated overall disease-control status in children with classic 21-OHD, but a single morning measurement provided no stable incremental information beyond A4 in this cohort. These findings do not support replacing A4 with 11KT or using 11KT as a standalone treatment target. Its potential clinical value may instead lie in contextual interpretation, particularly when conventional biomarkers and clinical findings are discordant.