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We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak post-stimulation GH < 5 micrograms/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 micrograms/l but < 10 micrograms/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 micrograms/l. Partial GHD and normal children 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 IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

To analyze the utility of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay in the diagnosis of growth hormone deficiency (GHD) we measured IGF-I and IGFBP-3 in sera from normal children (n = 309), short children (n = 99) and patients with GHD (n = 73). In 80% and 93% of classical GHD (cGHD), IGF-I and IGFBP-3 levels, respectively, were below the age-related cutoff levels (lower limit). In 81% and 88% of normal short children (NS), IGF-I and IGFBP-3 levels, respectively, were above the age-related cutoff levels. Thus, both IGF-I and IGFBP-3 were good parameters for screening GHD. In contrast, in more than half of partial GHD (pGHD), either IGF-I or IGFBP-3 was above the age-related cutoff levels. The poor discrimination between patients with pGHD and NS by using these two parameters may be the result of their relatively similar GH levels, as compared to cGHD, or due to the limitations of GH stimulation tests. In about 80-90% of NS, IGF-I and IGFBP-3 were above the age-related cutoff levels at all ages. A hundred percent of cGHD under 10 years old had IGFBP-3 below the age-related cutoff levels, whereas 79% of cGHD under 10 years old had IGF-I below the age-related cutoff levels. Thus in the younger age groups, IGFBP-3 may be more sensitive than IGF-I. It may be because IGFBP-3 levels are relatively higher than those of IGF-I in younger subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

To analyze the utility of insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay for diagnosis of growth hormone deficiency (GHD) we measured IGFBP-3 in sera from normal children, short children and patients with GHD. The sensitivity (true positive ratio) of IGFBP-3 for complete GHD (cGHD) was 93%, while the specificity (true negative ratio) for normal short children (NS) was 88%. In contrast, the sensitivity of IGFBP-3 for partial GHD (pGHD) was only 43%. The poor discrimination between patients with pGHD and NS may be the result of their relatively similar GH level, as compared to cGHD, or due to the limitations of GH stimulation tests. The specificity of IGFBP-3 for NS was excellent in children of all ages: less than 10 years old (87%) and older than 10 (88%). However, sensitivity for GHD was good for children less than 10 years old (84%) but poor for children older than 10 (64%). IGFBP-3 may be less sensitive for diagnosing GHD in older children because IGFBP-3 levels may also increase during puberty due to mechanisms independent of the GH-IGF-I axis.