The role of GH/IGF-1 axis dysfunction and inflammatory cytokines in pediatric short stature

Short stature in children is a common clinical condition frequently associated with abnormalities in the GH/IGF-1 axis. Emerging evidence points to the involvement of inflammatory cytokines and serum markers in modulating this dysfunction. This study aims to investigate the molecular pathways underlying GH/IGF-1 axis impairment and assess the levels of inflammatory cytokines and other related biomarkers in children with short stature.

A total of 150 children diagnosed with short stature were recruited from the endocrinology department of a tertiary care hospital. An ageand sex-matched group of 150 healthy children served as controls for comparison. Serum concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and other relevant biomarkers were measured using enzyme-linked immunosorbent assay (ELISA). Genetic testing was performed to detect mutations in genes involved in the GH/IGF-1 signalling pathway. Data analysis was conducted using SPSS software, with statistical significance set at p< 0.05.

Children with short stature showed significantly reduced GH and IGF-1 levels (p< 0.001) and elevated IL-6 and IL-8 levels (p< 0.01). A moderate negative correlation was found between IL-6 and IGF-1 levels (r=-0.45, p< 0.001), suggesting that inflammation may impair growth signalling. GHR gene mutations were significantly more common in the short stature group (14.7% vs. 2.7%, p< 0.001) and were associated with lower IGF-1 levels.

This findings of the study suggest that impaired GH/IGF-1 signalling, increased inflammatory cytokines, and a higher prevalence of GHR gene mutations collectively contribute to the pathophysiology of pediatric short stature. These results highlight the need for integrative diagnostic approaches and future therapeutic strategies that target both endocrine and inflammatory pathways.