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

Layla Damen,Anita C S Hokken-Koelega,Laura C G De Graaff,Melitza S M Elizabeth,Stephany H Donze,Sjoerd A A Van Den Berg

doi:10.3390/jcm11051280

Abstract

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.

Highlights

Our findings suggest that measuring serum free insulin-like growth factor (IGF)-I levels could contribute to the decision of whether or not to change the growth hormone (GH) dose when high immunoreactive IGF-I levels are found in a GH-treated child with Prader–Willi syndrome (PWS), when our results are confirmed in another study
We found a major discrepancy between serum immunoreactive IGF-I SD score (SDS) and free
Our findings show that immunoreactive IGF-I levels are not appropriate for GH dosing in children with PWS

Summary

Introduction

Prader–Willi syndrome (PWS) is a rare multisystem genetic disorder caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13 [1,2]. PWS is characterized by muscular hypotonia, short stature, abnormal body composition, developmental delay, behavioral problems and hyperphagia, which can result in severe obesity when uncontrolled [2–4]. The benefits of growth hormone (GH) treatment in children are well established, as GH improves body composition, psychomotor development, cognition and linear growth [5–9]. In children with PWS, the treatment with a standard GH dose often results in high serum immunoreactive insulin-like growth factor (IGF)-I levels, with levels often being

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