Boguszewski M, Bjarnason R, Rosberg S, Carlsson L M, Albertsson-Wikland K
Department of Pediatrics, University of Goteborg, Sweden.
J Clin Endocrinol Metab. 1997 Apr;82(4):1014-9. doi: 10.1210/jcem.82.4.3902.
This study was undertaken to characterize the serum levels of GH-binding protein (GHBP) before and during GH treatment in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters. Sixty-seven prepubertal short children (49 boys and 18 girls; height SD score, -5.4 to -2.0; age, 2.0-12.8 yr) born SGA, 8 of whom (6 boys and 2 girls) had signs of Silver-Russell syndrome, participated in the study. Total GHBP was measured by a ligand-mediated immunofunctional assay. The mean (SD) change in height SD score during the year before the start of GH treatment (0.1 IU/kg.day) was 0.11 (0.20) SD score, and this value increased to a 0.84 (0.43) SD score during the first year (P < 0.001) and to a 1.27 (0.63) SD score during the 2-yr period of therapy (P < 0.001). The baseline GHBP values ranged from 49-392 pmol/L, and no relationships were found among sex, chronological age, and maximal GH response to an arginine-insulin tolerance test. A positive correlation between GHBP and body composition, expressed as weight for height SD score, was found in the whole group (r = 0.28; P < 0.05) and in boys (r = 0.44; P < 0.01). No relationship was found between GHBP and spontaneous 24-h GH secretion, in terms of either GH secretion rate or pulsatile pattern, whereas GHBP was positively correlated with insulin-like growth factor I (IGF-I) SD score (r = 0.28; P < 0.05) and IGF-binding protein-3 SD score (r = 0.39; P < 0.01). Using a multiple stepwise linear regression analysis, the model using the IGF-binding protein-3 SD score and the weight for height SD score at the start of GH therapy accounted for 33% of the variance in the baseline GHBP values. A mean increase of 27 (51)% in GHBP levels was found after 1 yr of therapy. However, a high degree of variability in the response of individuals to GH treatment in terms of GHBP levels was observed: in some children GHBP levels increased, whereas in others they decreased. In conclusion, GHBP levels in short prepubertal children born SGA were mostly within the normal range previously reported and correlated directly with body composition. An increase in GHBP levels was observed during GH treatment in some SGA children. No correlation was found between pretreatment GHBP levels and growth response to GH treatment.
本研究旨在描述小于胎龄儿(SGA)出生的青春期前矮小儿童在生长激素(GH)治疗前及治疗期间血清生长激素结合蛋白(GHBP)水平的特征及其与生长参数的关系。67名SGA出生的青春期前矮小儿童(49名男孩和18名女孩;身高标准差评分,-5.4至-2.0;年龄,2.0 - 12.8岁)参与了研究,其中8名(6名男孩和2名女孩)有Silver-Russell综合征的体征。采用配体介导的免疫功能测定法测量总GHBP。在开始GH治疗(0.1 IU/kg·天)前一年身高标准差评分的平均(SD)变化为0.11(0.20)标准差评分,在第一年该值增加到0.84(0.43)标准差评分(P < 0.001),在2年治疗期间增加到1.27(0.63)标准差评分(P < 0.001)。基线GHBP值范围为49 - 392 pmol/L,未发现性别、实足年龄与精氨酸 - 胰岛素耐量试验的最大GH反应之间存在相关性。在整个组(r = 0.28;P < 0.05)和男孩中(r = 0.44;P < 0.01)发现GHBP与身体组成(以身高标准差评分表示的体重)呈正相关。就GH分泌率或脉冲模式而言,未发现GHBP与自发性24小时GH分泌之间存在相关性,而GHBP与胰岛素样生长因子I(IGF - I)标准差评分呈正相关(r = 0.28;P < 0.05),与IGF结合蛋白 - 3标准差评分呈正相关(r = 0.39;P < 0.01)。使用多元逐步线性回归分析,在GH治疗开始时使用IGF结合蛋白 - 3标准差评分和身高标准差评分表示的体重的模型占基线GHBP值方差的33%。治疗1年后发现GHBP水平平均增加27(51)%。然而,观察到个体对GH治疗在GHBP水平方面的反应存在高度变异性:在一些儿童中GHBP水平升高,而在另一些儿童中则降低。总之,SGA出生的青春期前矮小儿童的GHBP水平大多在先前报道的正常范围内,且与身体组成直接相关。在一些SGA儿童的GH治疗期间观察到GHBP水平升高。未发现治疗前GHBP水平与GH治疗的生长反应之间存在相关性。