CLINICAL UTILITY OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN THE EVALUATION AND TREATMENT OF SHORT CHILDREN WITH SUSPECTED GROWTH-HORMONE DEFICIENCY

We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, b ut not partial, growth hormone deficiency (GHD). In this study, we com pare IGFBP-3 levels in short children previously divided into groups o n the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak poststimulation GH < 5 mu g/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 mu g/l but < 10 mu g/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 mu g/l. Partial GHD and normal childre n with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP- 3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low TGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal I GF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whe ther IGFBP-3 can predict the response to GH treatment in prepubertal c hildren by comparing pretreatment IGFBP-3 with the height gain achieve d by 1 year of GH treatment. The incremental growth velocity during tr eatment correlated significantly with the pretreatment IGFBP-3 so scor e (N = 46 r = -0.80, p < 0.005). The baseline IGFBP-3 so score for all subjects correlated (N = 171, r = 0.51 p < 0.0001) with height. These data suggest that IGFBP-3 may reflect GH secretion status in most chi ldren being evaluated for GHD and that a low pretreatment IGFBP-3 so s core predicts improved growth during the first year of GH treatment.