Body composition in children and adolescents with non-classic congenital adrenal hyperplasia and the risk for components of metabolic syndrome: An observational study

Background: Treated or untreated non-classic congenital adrenal hyperplasia (NCCAH) diagnosed in childhood could pose an increased risk of obesity and metabolic derangements in adolescence and early adulthood. We aimed to explore the interaction between muscle-to-fat ratio (MFR) and components of metabolic syndrome in pediatric subjects with NCCAH.

Methods: This retrospective observational study was conducted in the Tel Aviv Medical Center from January 2018 to January 2022. The study group comprised 75 subjects (26 males) with NCCAH (61 hydrocortisone-treated [21 males] and 14 untreated [5 males]) and 134 healthy sex- and age-matched subjects (41 males) with normal puberty served as controls. Body composition was measured by bioelectrical impedance analysis (BIA) and muscle-to-fat ratio (MFR) z-scores were calculated. Stepwise linear regression models were applied to evaluate explanatory variables for MFR z-scores, blood pressure percentiles, lipid profiles, and glucose metabolism.

Results: The median age [interquartile range] was 7.5 years [5.3, 8.8] at NCCAH diagnosis and 12.3 years [8.9, 15.4] at BIA. The median cumulative hydrocortisone dose was 7620 mg/m² [2547, 12903]. Subjects with NCCAH had higher mean BMI z-scores and lower median MFR z-scores compared to controls [(0.47 ± 0.97 vs. -0.19 ± 1.04, p<0.001) and (-0.74 [-1.06, -0.14] vs.-0.37 [-0.99, 0.15], p=0.045), respectively]. The linear regression models dependent variables and their explanatory variables were: MFR z-score (R²= 0.253, p<0.001) - socioeconomic position index (β=0.348, p=0.003), birthweight z-score (β=-0.258, p=0.013), and duration of hydrocortisone treatment in years (β=0.048, p=0.023); systolic blood pressure percentile (R² = 0.166, p<0.001) - MFR z-score (β=-9.75, p<0.001); TG/HDL ratio (R² = 0.116, p=0.024) - MFR z-score (β=-0.300, p=0.024). No significant variables were found for glucose.

Conclusions: Children and adolescents with NCCAH have a body composition characterized by an imbalance between muscle and fat tissues, which may place them at increased risk for early-onset cardiometabolic derangements. It is reassuring that glucocorticoid therapy aimed to alleviate androgen overproduction does not appear to adversely affect their body composition.