Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature

Abstract

The causes for growth failure in children with idiopathic short stature (ISS) are not definitely established. Peripheral GH resistance due to changes at the level of the GH receptor has been suggested as one of the most probable explanation. In this study, we have selected a group of prepubertal children with ISS to evaluate the GHBP/receptor status by measuring the GH binding protein (GHBP) activity in plasma. Thirty prepubertal children with ISS (18 boys and 12 girls; age range: 4.79 to 11.33 yr) and twenty age-matched children with normal growth (11 boys and 9 girls) were studied. The ISS group presented growth retardation of -2.3 +/- 0.43 SD score (mean +/- SD) and normal GH secretion. Plasma IGF-I levels were below or in the low normal range (mean +/- SD: 136.3 +/- 62.3 micrograms/l, a concentration that was significantly different from IGF-I levels in the normal group (mean +/- SD: 187 +/- 57.5 micrograms/l p < 0.005). Plasma GHBP activity using a GH-binding/gel chromatography assay showed significantly lower values in ISS group (mean +/- SD: 7.17 +/- 1.5%) as compared with those of the control group (mean +/- SD: 12.02 +/- 2.04%; p < 0.001). There were no significant age- or sex-related differences in GHBP values in either group. The decreased GHBP levels observed in this group of children with ISS suggest that they may present a certain degree of GH insensitivity, probably due to a defect at the GH-receptor level.

Analysis of the intracellular signalling domain of the human growth hormone receptor in children with idiopathic short stature

“…The aetiology of ISS in the group of children in our study is unknown but endocrine investigations suggest they may have a degree of GHI with normal or elevated GH levels following provocation and low serum IGF-I levels (100% < 50th centile; 64.5% < 10th centile). Partial GHI has been reported by other groups in ISS, but principally in association with low serum GHBP activity (Carlsson et al, 1994;Attie et al, 1995;Goddard et al, 1995;Davila et al, 1996). GHBP levels in children in our study were normal, which led us to hypothesize that, if GHR gene defects were the cause of short stature in these subjects, they were.…”

Bone mineral status in prepubertal children with constitutional delay of growth and puberty

“…Causes for CDGP are far from clear. Children with this condition are included, in most studies, in idiopathic short stature, and, whereas normality in the GH secretory dynamics has been reported (22), there are studies that report an impaired GH secretion (23,24), decreased GH binding proteins (25,26) and mutations of the GH receptor in some children with idiopathic short stature (27). Therefore, an abnormality in the GH/IGF-I axis cannot be excluded as a possible factor for the poor mineral density found in CDGP.…”