ORF32-06 - Analysis of the Glucocorticoid Treatment in Relation to Growth Outcomes in a Cohort of 1500 Children with Congenital Adrenal Hyperplasia - Real-World Data from the I-CAH Registry

Background
Previous analysis from the I-CAH Registry has demonstrated substantial international and inter-centre variability in glucocorticoid (GC) replacement practices. We hypothesised that differing treatment strategies are associated with distinct clinical outcomes and that improved understanding of these relationships may support optimisation of hormone replacement in congenital adrenal hyperplasia (CAH). This study aimed to investigate the impact of GC dosing on growth outcomes, specifically height and weight, in children and young people with CAH.

Methods
We analysed longitudinal data from children with CAH recorded in the I-CAH Registry since 2003. Data were collected in collaboration with participating centres and analysed using multivariable regression models implemented in the R statistical platform. GC doses were standardised and expressed as hydrocortisone (HC) equivalents per body surface area (mg/m²/day), conversion rate: 20 mg hydrocortisone = 4 mg prednisolone = 500 mcg dexamethasone = 25 mg cortisone acetate. Associations between GC dose and height and weight standard deviation scores (SDS), adjusted for age and sex, were examined. SDS were calculated using Growth Analyser with WHO reference data.

Findings
Data from 1,571 patients encompassing 14,411 clinical visits across 23 countries and 60 centres were included. Marked international variability in GC dosing was observed, with median doses ranging from 5.0 to 20.6 mg HC-equivalent/m²/day. GC dose was significantly associated with the country of treatment (R²=0.08, p< 0.01). Height-SDS demonstrated an inverted U-shaped trajectory across childhood, with lower values in infancy (mean SDS -1.4), a peak in early childhood up to 9 years (mean SDS 0.5), followed by another a decline to a mean SDS -1.0 when reaching adult age (18 years). Multivariable analyses indicated that up to 53% of the variance in height-SDS was explained by weight-SDS, GC dose per body surface area, and country of treatment (under 9 years: R²=0.53, p< 0.01; over 9 years: R²=0.15, p< 0.01). Weight-SDS increased modestly with GC dose (R²=0.005, p< 0.01), although birth weight and country of origin were the strongest predictors (R²=0.16, p< 0.01).

Interpretation
This large-scale longitudinal analysis of real-world data highlights pronounced international variation in GC replacement practices for paediatric CAH. The findings indicate that GC dosing is associated with growth outcomes, particularly height. The reduced height SDS in infancy may have several explanations, including relatively high GC exposure during early life, underscoring the need for strategies that optimise replacement therapy while minimising the risk of overtreatment from infancy onwards.