Real-world data highlight cardiometabolic consequences of chronic glucocorticoid exposure and poor androgen control in classic congenital adrenal hyperplasia
Presenter: Oksana Lekarev, DO, Weill Cornell Medicine, New York, NY
Long-term risk of cardiometabolic comorbidities associated with glucocorticoid exposure and androgen control in classic congenital adrenal hyperplasia: a Cox proportional hazards analysis from the CAHtalog registry. Presented June 14, 2026.
Cardiometabolic risk increased with higher glucocorticoid exposure, while poorer androgen control was associated with incident hypertension in patients with classic congenital adrenal hyperplasia, according to a real-world analysis of data from CAHtalog, a comprehensive US registry of patients with this condition.
The analysis, presented at ENDO 2026, highlighted the cumulative long-term morbidity burden associated with chronic supraphysiologic glucocorticoid use and the clinical importance of androgen control, given the biologic and sex-specific effects of androgens on cardiometabolic risk, according to the investigators.
In view of the findings, the investigators suggested that treatment strategies that improve androgen control while making it possible to lower the glucocorticoid dose may help mitigate the long-term morbidity associated with classic congenital adrenal hyperplasia.
Registry supports patient-centered clinical research
Congenital adrenal hyperplasia requires lifelong glucocorticoid therapy for cortisol replacement, but controlling androgen excess typically requires supraphysiologic doses. Such exposure, variably associated with androgen oversuppression or persistent excess, may contribute to long-term morbidity.
Neurocrine Biosciences established the CAHtalog (Congenital Adrenal Hyperplasia: Patient and Clinical Outcomes in Real-World Practice Settings) registry in partnership with the CARES Foundation to characterize longitudinal treatment patterns in this condition and its natural history and impact. The database was designed to support patient-centered clinical research in congenital adrenal hyperplasia. Neurocrine Biosciences licenses the registry data from PicnicHealth.
Building on prior descriptive analyses, the investigators applied longitudinal time-to-event models to evaluate associations between glucocorticoid exposure, androgen control, and incident comorbidities. Outcomes included hypertension, overweight or obesity, and metabolic syndrome, defined using diagnosis codes and clinical measurements. As per monitoring guidance, investigators limited the analyses to patients older than 2 years.
Investigators used Cox proportional hazards models with age as the time scale, defining study entry at each participant's first registry record and censoring observations at the first occurrence of each outcome. Time-varying covariates included glucocorticoid dose, expressed as hydrocortisone equivalents (mg/m²/day); androstenedione levels, expressed relative to age- and sex-specific upper limits of normal; and overweight or obesity status, as appropriate.
The models were adjusted for sex, and investigators assessed model assumptions and statistical inference. Sensitivity analyses incorporated relevant concomitant medications and alternative measures of androgen control to evaluate the robustness of the findings.
Findings
Investigators analyzed data from the CAHtalog registry on 126 patients (40.5% male), with a mean follow-up period of 8.99 years (pediatric patients) and 12.94 years (adult patients). During the analysis period, 72 patients became adults.
In hypertension analyses (n = 107), each 1 mg/m²/day increase in glucocorticoid dose was associated with a 20% higher risk of incident hypertension (hazard ratio 1.20, P = .001) and each increase in androstenedione of 0.5 upper limits of normal was associated with a 29% higher risk (hazard ratio 1.29, P = .048), after multivariable adjustment.
Higher glucocorticoid exposure was consistently associated with an increased risk of overweight or obesity (hazard ratio 1.08, P = .048) and metabolic syndrome (hazard ratio 1.08, P = .27). For metabolic syndrome, investigators observed evidence that androgen levels confounded the association between glucocorticoid exposure and risk, with sex-specific interactions further influencing outcomes.
Study limitations include nonstandardized androstenedione timing relative to glucocorticoid dosing, gaps in longitudinal monitoring, and limited sample size.
Disclosures
No disclosures.
References
Lekarev O, Jahagirdar D, McKibbon C, et al. Long-term risk of cardiometabolic comorbidities associated with glucocorticoid exposure and androgen control in classic congenital adrenal hyperplasia: a Cox proportional hazards analysis from the CAHtalog registry. Presented at ENDO 2026, June 14, 2026, Chicago, IL.
Neurocrine Biosciences. CAHtalog. https://www.neurocrinemedical.com/cahtalog-data-access/ Accessed June 16, 2026.