Abstract
This nationwide study analyzed glucocorticoid treatment regimens and auxological outcomes in 349 Japanese patients with 21-hydroxylase deficiency (21-OHD) (145 males, 204 females; median (IQR) age 20.3 (14.7–30.8) years, of whom 98% had the classical form), using data from a 2017 follow-up survey. Hydrocortisone was used in all patients under 10 years (mean dose: 16.4 ± 3.6 mg/m2). In adults (≥21 years), 56/171 (33%) received hydrocortisone monotherapy, while others received synthetic glucocorticoids or combination therapies. The mean hydrocortisone-equivalent dose in adults was 18.5 ± 7.6 mg/m2, exceeding the 2014 Japanese guideline recommendations. Adult height (AH) standard deviation score (SDS) was –1.40 ± 1.05 for males and –1.32 ± 1.29 for females, with a significant negative correlation with age. The proportion of obesity in adults was notably high (30.2% in males, 40.0% in females). In adult females, a unique negative correlation was observed between hydrocortisone-equivalent dose and body mass index (BMI), possibly reflecting muscle wasting effects of high-dose glucocorticoids. Comparisons among three birth cohorts (post-newborn screening [NBS], pre-NBS, and pre-secular trend plateau) revealed significant improvements in the younger generation: the post-NBS group achieved significantly better AH SDS (males: –1.17 vs. –1.97, p = 0.033 for trend; females: –1.05 vs. –2.27, p = 0.001 for trend) and lower BMI (males: 23.0 vs. 27.5 kg/m2, p = 0.005 for trend; females: 23.0 vs. 28.2 kg/m2, p = 0.002 for trend) compared to the oldest generation. In conclusion, although glucocorticoid doses in this Japanese cohort remained relatively high, AH and BMI have significantly improved in younger generations. Continued optimization of glucocorticoid therapy is crucial to further enhance long-term health outcomes in patients with 21-OHD.
