Longitudinal Modeling and Simulation of Growth Hormone Efficacy in Children With Idiopathic Short Stature

Growth hormone (GH) has been widely used to treat idiopathic short stature (ISS), defined as a height that falls below the third percentile or 2 standard deviations below the mean for age and sex. This study aimed to evaluate the long-term effects of GH on relative growth response in children with ISS using a nonlinear mixed-effects (NLME) model for longitudinal data and to support personalized medicine through predictive modeling approach.

A total of 91 prepubertal patients with ISS were included in this study. The height percentile adjusted for age and sex was used as the outcome to reflect physiological growth, and the cumulative GH dose (mg/kg) was used as the exposure metric. A Gompertz-based NLME model was fitted to describe the dose-response relationship, and stepwise covariate modeling identified significant baseline predictors. The model performance was assessed using visual predictive checks and goodness-of-fit plots.

The final model estimated a baseline height percentile of 0.63 ± 0.90 and an upper growth limit of 17.2 ± 11.1. Body mass index, insulin-like growth factor-binding protein 3, and paternal height were significant covariates influencing the total growth.

This study demonstrated the utility of NLME modeling for quantifying the treatment response to GH in patients with ISS. The developed model was integrated into a web-based tool, allowing clinicians to predict individualized growth trajectories and optimize GH treatment strategies in real-world practice.