Cardiometabolic Risks in Youth with Congenital Adrenal Hyperplasia: A PEDSnet Analysis

Overview

This large multisite study using PEDSnet data demonstrates that youth with congenital adrenal hyperplasia (CAH) have significantly increased odds of cardiometabolic diagnoses including overweight/obesity, hypertension, dysglycemia, dyslipidemia, and liver dysfunction compared to matched controls. The risk is particularly pronounced in those with classic CAH, who show markedly higher odds of hypertension and liver dysfunction.

Background

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders primarily caused by 21-hydroxylase deficiency, leading to cortisol and aldosterone deficiencies and androgen excess. Classic CAH, the more severe form, requires lifelong glucocorticoid and mineralocorticoid replacement therapy. Despite treatment advances improving survival, individuals with CAH experience alternating periods of hormone imbalance that may predispose them to adverse cardiometabolic outcomes. Prior studies have been limited by small sample sizes and single-center designs, leaving gaps in understanding the broader cardiometabolic risk profile in youth with CAH.

Data Highlights

Key Findings

• Youth with CAH have over threefold increased odds of overweight/obesity compared to matched controls.
• Hypertension risk is significantly elevated in CAH, with classic CAH patients exhibiting an eightfold increase in odds.
• Dysglycemia and dyslipidemia are also more common in youth with CAH, indicating early metabolic disturbances.
• Liver dysfunction diagnoses are approximately doubled in both all CAH and classic CAH groups relative to controls.
• The study utilized a large, multisite electronic health record database (PEDSnet) with propensity score matching to robustly compare CAH patients to controls.

Clinical Implications

Clinicians should be vigilant in monitoring cardiometabolic health in youth with CAH, especially those with the classic form, given their substantially increased risk of obesity, hypertension, and metabolic abnormalities. Early identification and management of these risk factors may help mitigate long-term cardiovascular morbidity. Multidisciplinary care including endocrinology, cardiology, and nutrition may be warranted to optimize outcomes.

Conclusion

Youth with congenital adrenal hyperplasia, particularly classic CAH, are at markedly increased risk for adverse cardiometabolic diagnoses. This large-scale study underscores the need for proactive cardiometabolic risk assessment and intervention in this vulnerable population.

References

1. Speiser et al. 2010 -- Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline
2. Falhammar et al. 2015 -- Mortality in Patients with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
3. Merke & Bornstein 2005 -- Congenital Adrenal Hyperplasia
4. PEDSnet Data Coordinating Center -- PEDSnet Clinical Research Network