Bioactive Insulin-like Growth Factor (IGF)-I Concentrations in Children on Growth Hormone Therapy

Background Monitoring Insulin-like Growth factor (IGF)-I concentration is recommended during Growth Hormone (GH) therapy (GHT) in children. Supranormal levels of total IGF-I have raised concerns of long-term risks. Aim To evaluate bioactive and total IGF-I in healthy and in GH treated children and adolescents. Material and method A reference population of 570 children (59% girls) from the Copenhagen Puberty Study (COPUS) III and 126 short children (36% girls) with GHD and other non-GHD conditions. We established pediatric, sex-specific reference ranges of serum concentrations of bioactive IGF-I (KIRA) and compared with total IGF-I and IGF-I/IGFBP-3 molar ratio (iSYS) and total IGF-I, -II, IGFBP-3 and ALS (LC-MS/MS) in a subgroup. Further, we compared IGF-I bioactivity with total IGF-I, IGFBP-3 (iSYS) and IGF-I/IGFBP-3 molar ratio during GHT. Results Bioactive IGF-I increased with age in healthy children and correlated positively with total IGF-I and IGF-I/IGFBP-3 in healthy males (r=0.61 and r=0.57; p<0.001) and females (r=0.58 and r=0.59; p<0.001) and with IGF-I, -BP-3 and ALS (LC-MS/MS) (r=0.56, r=0.29 and r=0.38; p<0.001). Bioactive IGF-I and IGF-II (r=-0.29; p<0.001) correlated negatively. In 13% (17/126) of the patients bioactive IGF-I was above +2SD whereas total IGF-I was above +2SD in 25% (32/126) patients. Nine patients had both total and bioactive IGF-I above +2SD. In the non-GHD groups bioactive IGF-I SDS were lower than IGF-I SDS (p=0.015). Conclusion Bioactive IGF-I was within reference ranges in the majority of GH treated children. Monitoring bioactive IGF-I may help optimize GH dosing in specific patient subgroups.