ESPE Abstracts

Introduction: In congenital adrenal hyperplasia (CAH), glucocorticoid (GC) treatment must perform two functions – to replace cortisol deficiency and to suppress the excess production of adrenal androgens. Unfortunately, androgen suppression usually requires supraphysiologic GC doses, which are associated with serious comorbidities. Our study examined the exposure or dose-dependent relationships between GCs and GC-related adverse events (GCRAEs) and comorbidities in the classic CAH population.

Methods: Using a cross-sectional analysis of an all-payer U.S. claims database from 2014-2021, we identified classic CAH patients using ICD codes and GC prescription data. Mean age was 42±16 years, 67% female. Participants were stratified by average daily GC dose, expressed in hydrocortisone equivalents (HCe): Low (10-20mg/d HCe, n=480), med (>20-30mg/d HCe, n=574) and high (>30mg/d HCe, n=965). Using an average adult BSA of 1.79mg/m2, the low dose group was designated as approximately physiologic dosing (5.6-11.2mg/m2/d). The low dose group was used as the reference and its GCRAE rates were compared against those of the medium and high dose groups using chi-squared tests.

Results: When evaluated by System Organ Class (SOC), trends were seen between increasing daily GC dose and increasing rates of GCRAEs for cardiovascular disorders, GI disorders, energy/sleep disorders, and infections. Significant differences were seen at the SOC level between the low (approximately physiologic) and high dose groups in cardiovascular disorders such as tachycardia, syncope/collapse, and cardiomegaly (P=0.0118), in energy/sleep disorders (specifically weakness) (P=0.0029), and infections such as pneumonia, sepsis, cellulitis, bronchitis (P=0.0062). When evaluated by individual disorder code, significant differences between the high and low dose groups included anxiety disorders (P=0.0196), hypertensive chronic kidney disease (P=0.0397), and abnormal weight gain (P=0.0003). Significant differences were seen between the approximately physiologic dose group and the medium dose group for bacterial infections NOS (P=0.0471), hypertensive chronic kidney disease (P=0.0157), and hyperglycemia (P=0.0312).

Conclusions: This study identified GCRAEs that displayed a dose-dependent relationship with GC exposure. As the average daily GC dose increased, so did the rates of CV disorders, GI disorders, energy/sleep disorders, and infections. In addition, rates of multiple GCRAEs were significantly increased in the groups on supraphysiologic dosing. Given the cumulative risks of lifelong exposure to supraphysiologic GC doses in classic CAH patients, this study highlights the need for steroid-sparing therapies in this population.