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

Abstract

Context: 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.

Objective: This study aimed to characterize the clinical burden associated with CAH and quantify the degree to which CAH- and/or GC-related complications manifest.

Methods: 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.

Results: 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.

Conclusion: 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.