Endocrine Abstracts

JOINT2906

Context: The standard treatment for congenital adrenal hyperplasia (CAH) in childhood includes hydrocortisone and, for salt-wasting CAH, fludrocortisone supplementation. Regular monitoring and dose adjustments are essential to prevent over- or under-dosing during growth and puberty. Conventional fast-acting hydrocortisone often fails to adequately suppress the early morning surge of 17-OH progesterone (17OHP), and the requirement for three daily doses poses adherence challenges. In 2021, the European Medicines Agency approved hydrocortisone modified-release capsules (HMRC, Efmody®) for children aged 12 and older with CAH. Its modified release allows for twice-daily dosing, with the highest dose at bedtime, better replicating physiological cortisol secretion by achieving peak levels in the early morning.

Objective: To investigate growth, pubertal development, safety, long-term disease control and dosage of hydrocortisone and fludrocortisone in children and youth with CAH treated with HMRC and monitored by 17OHP saliva profiles.

Methods: This study is a retrospective, descriptive analysis of CAH patients treated at a single-center outpatient clinic. Linear mixed models (LMMs) are used to compare the average growth rate of parental target height and BMI before and after switching to hydrocortisone modified-release capsules (HMRC). Additionally, average dosage, blood pressure, and 17OHP level before and after switch are calculated using LMMs. The LMMs account for patient heterogeneity in time-dependent changes. Pubertal status is assessed using breast stage in females and testicular stage in males.

Results: Since September 2021, 42 children with CAH (22 males) have been treated with hydrocortisone modified-release capsules (HMRC). At the time of treatment switch, the median age was 11 years (IQR 8–14), with 16 children classified as prepubertal, 17 as pubertal, and 9 as postpubertal. Prior to the switch, growth rates were accelerated (0.10 z-scores/year, CI: 0.04–0.15, P<0.001), whereas a deceleration was observed afterward (−0.05 z-scores/year, CI: −0.15 to 0.04), particularly in (pre-)pubertal patients (0.13 vs. −0.12). The average hydrocortisone dosage increased by 3.25 mg/m² per day upon switching from immediate-release hydrocortisone to HMRC. Morning 17OHP levels suggested underdosage before the switch (323 ng/l, CI: 250–396) and improved control afterward (228 ng/l, CI: 167–289, P<0.01). No increase in adrenal crises was observed.

Conclusion: HMRC treatment in children with CAH improves morning pre-dose 17OHP levels, while growth rates align more closely with the parental target height. No significant adverse effects or severe complications were observed. Further research is needed to assess long-term outcomes and quality of life.