Recombinant human growth hormone therapy induces dose-dependent increases in uric acid and bilirubin in children with idiopathic short stature a retrospective cohort study

Objective This study aimed to examine the dose-dependent effects of recombinant human growth hormone (rhGH) therapy on uric acid (UA) and bilirubin metabolism in prepubertal children with idiopathic short stature (ISS) and to identify independent predictors of UA elevation. Methods We conducted a retrospective cohort study of 120 prepubertal children with ISS (57 boys, 63 girls) treated with rhGH (0.15–0.2 IU/kg/day) between 2019 and 2023. Serum UA, total bilirubin (TBIL), and direct bilirubin (DBIL) levels were collected at baseline and at 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment. Metabolic trajectories were analyzed using repeated-measures ANOVA. Multivariable logistic regression was used to identify risk factors, adjusted for age, sex, baseline BMI, and baseline UA. Results UA levels increased significantly from 291.7 ± 75.3 µmol/L at baseline to 368.3 ± 122.0 µmol/L at 24 months (Δ + 76.6 µmol/L, p < 0.001). A dose-dependent relationship was observed at 6 months (r = 0.269, p = 0.020) and 9 months (r = 0.262, p = 0.022). Independent predictors of UA elevation included baseline UA (OR = 1.15 per 10 µmol/L increase, 95% CI 1.05–1.26, p = 0.003) and ΔBMI SDS (OR = 2.18, 95% CI 1.03–4.64, p = 0.043). rhGH dose was also positively correlated with TBIL (r = 0.269, p = 0.020) and DBIL (r = 0.265, p = 0.020) at 6 months. Each 0.05 IU/kg/day increment in rhGH dose was associated with an eightfold increase in the risk of bilirubin elevation (OR = 8.00, 95% CI 2.15–29.70, p = 0.002). A linear regression model projected that children with baseline UA > 300 µmol/L receiving doses > 0.15 IU/kg/day would maintain UA levels above the hyperuricemia threshold (360 µmol/L) at 24 months. Conclusion rhGH therapy exerts dose-dependent effects on UA and bilirubin metabolism in clinical practice. We recommend intensified monitoring (every 3–6 months) for children with baseline UA > 300 µmol/L or on rhGH doses > 0.15 IU/kg/day, along with evaluation of insulin resistance and hepatic function. Long-term metabolic surveillance is advised for high-risk children undergoing rhGH treatment.