ESPE Abstracts

Introduction: Rege et al. (2018) demonstrated that 11-keto-testosterone (11KT) is the dominant androgen in girls during adrenarche. Claahsen-van der Grinten et al. (2022) proposed C19 oxysteroids as a potential parameter for therapeutic control in congenital adrenal hyperplasia (CAH). Turcu et al. (2016) observed a significant elevation in C19 oxysteroids in patients with 21-hydroxylase deficiency (21OHD). Currently, C-19 oxysteroids are not routinely measured, and there are no established paediatric reference values.

Method: We developed an LC-MS/MS method to determine 11KT and 11-keto-androstenedione (11KA4). We extracted serum and plasma samples (0.1 mL) using solid phase extraction (SPE). We included 412 healthy children (140 males, 272 females, aged 0-18 years) using residual material from blood checks. A complete steroid hormone profile was available for all children, with BMI known for 409 and Tanner stage B for 249 girls and Tanner stage G for 107 boys. Furthermore, five samples from children with 21-hydroxylase deficiency (21OHD) and five samples from children with 11-β-hydroxylase deficiency (11OHD) were determined.

Results: The method was linear from 0,5 nmol/L up to 50 nmol/L for both hormones. The lowest limit of quantification (LLOQ) was 36 pmol/L. The coefficient of variation was highest for 11KT at 9% and for 11KA at 11%. Prepubertal (<8 years) girls (mean 0.50 nmol/L) have significantly higher 11KT values than boys (mean 0.21 nmol/L) (P < 0.001). With the onset of thelarche, 11KT values in girls increase significantly from 0.54 nmol/L (mean, Tanner B1) to 0.94 nmol/L (Mean, Tanner B2-5) (P < 0.0001). In boys, 11KT increases significantly with the onset of gonadarche from 0.54 nmol/L (mean, Tanner G1) to 0.89 nmol/L (mean, Tanner G2-5) (P < 0.001). Higher values for 11KT were observed in patients with 21OHD (mean 2.7 nmol/L). In contrast, patients with 11OHD exhibited values within the range of the LLOQ.

Conclusion: Age- and gender-specific reference values for 11KT and 11KA4 have been established. These values can serve as a foundation for future assessments of C19 oxy steroids. It has been demonstrated that the concentration of 11KT increases in both boys and girls with the onset of puberty. The data from the CAH cohort confirm that 11KT levels can be elevated in 21OHD. Further studies are required to determine the extent to which this is dependent on the therapy setting.