Endocrine Abstracts

JOINT625

Background: Congenital Adrenal Hyperplasia (CAH) is a genetic disorder requiring lifelong corticosteroid replacement to manage cortisol insufficiency and androgen excess. Hydrocortisone, prednisone, and dexamethasone are the primary glucocorticoids used, yet dosing, timing, and long-term impacts vary.

Objectives: This review evaluates the effectiveness and safety of hydrocortisone, prednisone, and dexamethasone replacement therapies in pediatric-CAH patients, focusing on their impact on growth, androgen suppression, and cognitive outcomes.

Methods: We synthesized findings from 25 studies published between 2000 and 2024 that assessed corticosteroid replacement therapies in children and adolescents with CAH. Data were collated on drug type, dose, patient age, and primary outcomes, including growth metrics, metabolic health, androgen control, and cognitive effects.

Results: 1. Hydrocortisone (10–20 mg/m²/day in divided doses) was the most frequently studied replacement therapy. Monitoring of 17-hydroxyprogesterone was critical for dose optimization to prevent overtreatment. Studies revealed:

• Optimal Dosing: Three- or four-times-daily regimens closely mimic natural circadian rhythms, effectively reducing androgen excess and avoiding adrenal crises.

• Growth and Metabolism: Higher doses correlated with reduced adult height predictions but minimized androgen excess when appropriately adjusted.

• Advancements: Granule formulations allowed precise dosing in younger children, enhancing growth outcomes.

2. Prednisone (1–5 mg/day, single or twice-daily dosing) showed:

• Growth Impact: Comparable linear growth to hydrocortisone in lower doses but increased growth suppression during puberty.

• Androgen Suppression: Adequate suppression of 17-OHP and androstenedione, with fewer metabolic side effects than dexamethasone.

• Clinical Use: Prednisone offered convenience in older children requiring less frequent

3. Dexamethasone (0.1–0.27 mg/m²/day or prenatal dosing) provided robust androgen suppression but raised concerns about cognitive and metabolic effects:

• Growth: Low doses-controlled androgen secretion effectively while maintaining normal bone age progression.

• Cognition: Prenatal exposure in CAH-unaffected fetuses resulted in verbal working memory issues and social anxiety, highlighting the need for cautious use.

• Novel Approaches: Ultra-low doses preserved endogenous cortisol production in nonclassical CAH patients.

Discussion: Hydrocortisone remains the preferred corticosteroid for pediatric CAH due to its safety and ability to replicate physiological cortisol rhythms closely. Prednisone offers convenience for older children but may compromise growth during puberty. Dexamethasone, while effective for androgen suppression, warrants caution due to cognitive risks, particularly with prenatal exposure.

Conclusion: Tailoring corticosteroid therapy is critical in CAH management. Hydrocortisone remains the gold standard, while prednisone and dexamethasone serve specific roles, requiring precise dosing to balance efficacy and safety.

This synthesizes the need for individualized treatment strategies and monitoring to optimize outcomes in pediatric CAH patients.