Abstract

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment.

Highlights

  • Recombinant human growth hormone therapy is widely used for short stature due to various causes, such as chromosomal/genetic abnormalities, small for gestational age (SGA), idiopathic short stature (ISS), and idiopathic GH deficiency (IGHD) [1]

  • Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 (IGFBP-3) levels and peak GH level with the GH stimulation test were significantly decreased in CGHD group compared with PGHD (p < 0.05), whereas the sex ratio, age, bone age (BA), height, weight, body mass index (BMI), initial Recombinant human growth hormone (rhGH) dose did not differ among the groups

  • BA, IGF-I standard deviation score (SDS), initial rhGH dose, and peak GH level in the GH stimulation test were significantly low, and weight and BMI were showed the opposite trend in the IGHD group (p < 0.05) compared with ISS and SGA groups

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Summary

Introduction

Recombinant human growth hormone (rhGH) therapy is widely used for short stature due to various causes, such as chromosomal/genetic abnormalities, small for gestational age (SGA), idiopathic short stature (ISS), and idiopathic GH deficiency (IGHD) [1]. Relationship between serum IGF-I/IGFBP-3 and height in rhGH therapy disease, the response of increased height has been reported, and many researchers are striving to find a suitable factor that can reflect the safety and efficiency of rhGH [1,2,3,4,5]. Serum IGF-I and IGF binding protein (IGFBP)-3 levels depend on GH levels under normal physiological conditions [7]. IGFBP-3 is a carrier protein of IGF-I, regulating the activity of IGF-I, the relationship is vague in rhGH therapy [6]. Only a limited amount of previous clinical data has been reported comparing the growth response to long-term rhGH therapy using IGF-I and IGFBP-3 levels in ISS and SGA cases to those in IGHD [12,13,14]

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