Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children

Background: The serum insulin-like growth factor-1 (IGF-1)/insulin-like growth factor binding protein-3 (IGFBP-3) ratio has various potential applications in growth hormone-related disorders. This study aimed to investigate the performance of the IGF-1/IGFBP-3 ratio, independently and in combination with serum IGF-1 and IGFBP-3, in the diagnosis of growth hormone deficiency (GHD) in children with short stature (SS). Methods: A 7-year cross-sectional observational study was conducted on 235 children with SS. Participants with known disorders that may affect IGF-1 other than GHD were excluded. Participants were classified into GHD (n = 64) and non-GHD (n=171) groups. GHD was defined as a slow growth rate (<25th percentile over 1 year) and suboptimal growth hormone (GH) response to 2 GH stimulation tests (peak GH<6.25 ng/mL using the DiaSorin Liaison assay). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio, independently and in various combinations, were determined. Results: GHD was diagnosed in 27.2% of participants. Among all studied variables, a low serum IGF-1/IGFBP-3 ratio demonstrated the greatest sensitivity for GHD (87.5%), with a comparable specificity (83.0%). The combination of low serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for GHD (97.7%), whereas the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of SS (100.0%). Conclusion: Our data suggest that the serum IGF-1/IGFBP-3 ratio is a useful marker for the diagnosis of GHD in children who do not have other disorders that may affect serum IGF-1 levels. Further large studies are needed to confirm the diagnostic utility of the serum IGF-1/IGFBP-3 ratio.