Bioactive IGF-I Concentrations in Children on GH Therapy

Abstract

Background: Monitoring IGF-I concentration is recommended during GH therapy 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.

Materials and methods: A reference population of 570 children (59% girls) from the Copenhagen Puberty Study III and 126 short children (36% girls) with GH deficiency (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 acid labile subunit (liquid chromatography-tandem mass spectrometry) in a subgroup. Further, we compared IGF-I bioactivity with total IGF-I, IGFBP-3 (iSYS) and IGF-I/IGFBP-3 molar ratio during GH therapy.

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 < .001) and females (r = 0.58 and r = 0.59; P < .001) and with IGF-I, BP-3, and acid labile subunit (liquid chromatography-tandem mass spectrometry) (r = 0.56, r = 0.29, and r = 0.38; P < .001). Bioactive IGF-I and IGF-II (r = -0.29; P < .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 = .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.

Keywords: GH therapy; IGF-I; IGFBP-3; LC-MS/MS; bioactive IGF-I; rhGH.