2026-07-07 | Modified-release hydrocortisone (Efmody®) in children with congenital adrenal hyperplasia: a retrospective registry study

Background Replacement therapy for congenital adrenal hyperplasia (CAH) in childhood includes hydrocortisone and, in salt-wasting forms, addition of fludrocortisone. Immediate-release hydrocortisone often fails to adequately suppress early morning 17-hydroxyprogesterone (17OHP) levels. Hydrocortisone modified-release capsules (HMRC, Efmody ® ) were approved by the EMA in 2021 for the treatment of patients aged ≥12 years with CAH. This study evaluates the efficacy and safety of HMRC in children and adolescents based on real-world data collected from the I-CAH registry. Methods A single-center retrospective analysis of children with CAH was conducted. Linear mixed models (LMMs) were used to calculate pre–post comparisons of 17OHP saliva profiles, growth rate, bone age, body mass index, hydrocortisone and fludrocortisone dosage, blood pressure, and safety parameters before and during HMRC therapy (study registration, https://drks.de/search/de , DRKS00038319). Findings The median age of the 36 children with CAH at the time of treatment switching to HMRC was 10 years (interquartile range [IQR]: 8–14 years). Of these, 15 were prepubertal and 21 were (post)pubertal. HMRC therapy was associated with a deceleration of previously increased growth velocity (pre-switch: 0.1 SDS/year, 95% CI: 0.0 to 0.2; post-switch: -0.1 SDS/year, 95% CI: –0.2 to 0.1) and with a reduction of median difference of bone age and chronological age by 0.50 years (IQR -1.17–0.27, range -2.2–2.00). Mean hydrocortisone dose increased by 2.4 mg/m²/day during HMRC treatment. Mean morning 17OHP concentrations significantly decreased from 337 ng/L (95% CI: 240–437) to 214 ng/L (95% CI: 155–294) after switching to HMRC treatment. No adrenal crisis was observed. Interpretation Twice-daily HMRC therapy can also improve CAH therapy in children and adolescents in terms of hormonal control and growth.

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2026-06-19 | Clinical burden of classic congenital adrenal hyperplasia and glucocorticoid-related complications: a claims analysis.

Classic congenital adrenal hyperplasia (CAH) is a rare genetic condition characterized by impaired cortisol and aldosterone synthesis. Historical management required glucocorticoid (GC) therapy to replace cortisol and, often, to suppress excess ACTH and adrenal androgens. However, supraphysiologic GC doses can lead to substantial complications. This study aimed to characterize the clinical burden associated with CAH and quantify the degree to which CAH- and/or GC-related complications manifest. Retrospective cohort analyses were conducted using administrative claims data from MarketScan® Research Databases (1/1/2020-12/31/2022) to quantify the burden of CAH- and/or GC-related complications among insured patients with CAH in the United States compared with a matched cohort. A total of 719 patients with CAH receiving GC therapy were matched 1:5 with 3595 individuals based on age, sex, payer, region, and enrollment duration. Patients with CAH had significantly higher rates of predominantly GC-related complications, including cardiovascular/circulatory diseases, type 2 diabetes, hypertension, hyperglycemia, metabolic complications, obesity, and osteoporosis (all P < .05). Patients with CAH demonstrated significantly higher rates and risks of nearly all CAH-related complications compared with matched controls (P < .05). Rates and risks of nearly all complications categorized as both CAH- and GC-related were significantly higher among patients with CAH (P < .05). Rates were consistently higher in adults than pediatric patients, underscoring the progressive and cumulative nature of CAH- and GC-related morbidity. Individuals with CAH experience higher rates and risks of CAH- and/or GC-related complications, highlighting the considerable burden associated with CAH and supraphysiologic GC treatment. Higher complication rates in adults emphasize the need for early and effective management of CAH. Novel non-GC therapies may enable GC dose reduction while maintaining androgen control, potentially mitigating these complications.

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2026-06-03 | Advances in pharmacological treatment for congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH), most commonly caused by 21-hydroxylase deficiency, remains associated with substantial morbidity despite life-saving glucocorticoid replacement. This review is timely because several novel therapies have recently emerged with the potential to improve disease control while reducing glucocorticoid burden. Recent advances in CAH management include modified-release hydrocortisone, which better mimics physiological cortisol secretion and may improve androgen control with lower glucocorticoid exposure. Steroid-reducing agents have advanced rapidly, particularly the corticotropin-releasing factor type 1 receptor antagonist crinecerfont and the melanocortin 2 receptor (MC2R) antagonist atumelnant, both of which show promise in lowering adrenocorticotropic hormone (ACTH)-driven androgen excess and facilitating glucocorticoid dose reduction. Additional emerging approaches include insurmountable MC2R antagonists and the anti-ACTH monoclonal antibody Lu AG13909. Gene therapy and genome editing strategies are also progressing, although important biological and technical barriers remain, particularly for durable adrenal targeting. The therapeutic landscape for CAH is evolving rapidly beyond conventional steroid replacement. These innovations may improve biochemical control and long-term outcomes, but challenges remain regarding adrenal crisis risk, long-term safety, durability, cost, and global equity of access.

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