Free Insulin-like Growth Factor (IGF)-I in Children with PWS

In children with Prader−Willi syndrome (PWS), the standard growth hormone (GH) dose often results in high immunoreactive IGF-I levels. These high immunoreactive IGF-I levels lead to concern because their long-term effects are unknown. As a result, clinicians have to lower the GH dose, which worsens body composition and quality of life. As clinical features do not seem to correspond to immunoreactive IGF-I values, it is questionable whether immunoreactive IGF-I is a suitable marker for GH dosing, or whether another parameter better reflects IGF-I bioavailability and bioactivity. We, therefore, investigate serum immunoreactive IGF-I, free IGF-I and IGFBP-3 levels in 70 GH-treated children with PWS. Our study showed that, although immunoreactive IGF-I levels were high (>2 SDS) in the vast majority of prepubertal and pubertal children, free IGF-I SDS levels were <0 SDS in most and <1 SDS in all. Free IGF-I correlated with the immunoreactive IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio. We conclude that there is a major discrepancy between immunoreactive and free IGF-I levels. While in the majority of GH-treated children with PWS, immunoreactive IGF-I levels were high, free IGF-I levels were <0 SDS in most. Our data appear to be very reassuring and suggest that free IGF-I levels should also be taken into consideration when the immunoreactive IGF-I levels are >2 SDS in GH-treated children with PWS.