Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Investigating the 11-oxyandrogens and 21-deoxycortisol for therapeutic monitoring of congenital adrenal hyperplasia (143961)

Jennifer L Ng 1 2 , Lauren T Tyack 2 , Ee Mun Lim 3 4 , Rui Zhang 3 , Suzanne J Brown 4 , Gerald F Watts 5 , Bronwyn G.A. Stuckey 2 4
  1. Hollywood Consulting Centre, Nedlands, WA, Australia
  2. The Keogh Institute for Medical Research, Nedlands, WA, Australia
  3. Chemical Pathology, PathWest QEII Laboratory, Nedlands, WA, Australia
  4. Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  5. Head of Cardiometabolic Service, Royal Perth Hospital, Perth, WA, Australia

Background: Biochemical monitoring of classic 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) relies on serum measurements of 17-hydroxyprogesterone (17OHP), androstenedione (A4) and testosterone (T). High biological variability, particularly of 17OHP, limits interpretation of results and makes therapeutic adjustments based on single measurements challenging (1). Aims: We aimed to investigate the biological variability of the 11-oxyandrogens and 21-deoxycortisol (21DF) and to compare steroid concentrations between poorly and adequately controlled patient samples as defined by serum A4 concentrations. Method: In this prospective study, repeated LC-MS/MS androgen profiles were performed in 21 women with classical CAH referred by Endocrinologists from the Keogh Institute, WA, between April 2022 and June 2025. The biological component of the intra-individual coefficient of variation (CVB) was calculated for each analyte. Serum concentrations of four 11-oxyandrogens and 21DF were compared between samples in adequate versus poor biochemical control as judged by A4 levels within or above age and sex appropriate reference ranges. Results: There were 74 observations among the 21 participants. The CVB was lowest for 11OHT (33.7%) and 11KA4 (41.8%) and highest for 21DF (157.5%). Of the conventional biomarkers, CVB was lowest for T (47.0%) and A4 (60.5%) and highest for 17OHP (107.9%). Median concentrations of all steroids were lower in adequately versus poorly controlled samples (all p-values <0.0001). When A4 was within range, all four 11-oxyandrogens and T were within published normative ranges (2). However, 17OHP and 21DF remained elevated in adequately controlled samples. Conclusions: These results support recommendations to aim for A4 and T within the upper-normal range while allowing 17OHP and 21DF to remain elevated to avoid glucocorticoid over-replacement. The 11-oxyandrogens may be superior to conventional biomarkers for therapeutic monitoring given their lower biological variability and adrenal-specificity. Normalising 11KT, a potent adrenal-specific androgen may be a reasonable therapeutic goal. Larger studies including children and men are required.

  1. 1. Speiser, P. W., et al. (2018). "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline." The Journal of Clinical Endocrinology & Metabolism 103(11): 4043-4088.
  2. Schiffer L, Kempegowda P, Sitch AJ, Adaway JE, Shaheen F, Ebbehoj A, et al. Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation. European journal of endocrinology. 2023;188(1)