Longitudinal unraveling: The impact of recombinant human growth hormone on spontaneous brain activity in children with short stature–A resting-state fMRI study

Recombinant human growth hormone (rhGH) is an approved method to improve the growth and ameliorate behavioral issues in children with short stature. However, the data concerning the effects of rhGH treatment on spontaneous brain activity remains unclear. This study included 35 children with short stature, categorized into two groups: the treated group (n = 14) and the untreated group (n = 21). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessments at baseline and at the end of a one-year follow-up. The rs-fMRI based amplitude of low frequency fluctuation (ALFF) analysis method was employed to assess spontaneous brain activity. Interaction effects between rhGH and time on ALFF were detected using a mixed-effects analysis. Additionally, Stepwise regression analysis was conducted to investigate the associations between ALFF values and significant clinical indicators. The treated group exhibited significant improvements in height, weight, insulin-like growth factor-1 (IGF-1) levels, insulin-like growth factor binding protein 3 (IGFBP-3) levels, and processing speed index (PSI) when reevaluated from baseline. The interaction effect of rhGH × time was evident in the right putamen (RPUT), where the ALFF value showed a significant increase following rhGH treatment, while also demonstrating a notable positive correlation with height. Moreover, The main effect of time was manifested as a significant decrease in the ALFF value of the left dorsolateral superior frontal gyrus (LSFG) within the untreated group during the follow-up period, concurrently displaying a positive correlation with age. In conclusion, rhGH treatment not only has a positive effect on the growth, cognition, and behavior of children with short stature, but also improves and normalizes spontaneous brain activity.