Thalange N K, Price D A, Gill M S, Whatmore A J, Addison G M, Clayton P E
University Department of Child Health, Royal Manchester Children's Hospital, Pendlebury, United Kingdom.
Pediatr Res. 1996 May;39(5):849-55. doi: 10.1203/00006450-199605000-00018.
GH insensitivity may be an inherited condition or may arise as a consequence of disease of malnutrition. Laron syndrome is the most severe form of GH insensitivity, arising from an absent or defective GH receptor. Less severe forms of GH insensitivity, however, may exist, resulting in short stature but in few other features of Laron syndrome. We have identified a heterogeneous group of children with short stature and either high basal (> 10 mU/L) or high peak GH levels (> 40 mU/L) on GH provocation testing, to examine biochemical markers of GH sensitivity. These children received 4 d of GH (0.1 U/kg) and the increment in IGF-I, IGF binding protein (BP)-3, and GHBP was determined. Eight GHD children, commencing GH therapy, were recruited as positive controls. The two groups could not be differentiated by age, height SDS (SD score), height velocity SDS, or body mass index. IGF-I and IGFBP-3 generation were correlated in all children (delta SDS IGF-I versus delta SDS IGFBP-3, r = 0.49, p = 0.03). Neither basal GHBP levels or the increment in GHBP were predictive of the IGF-I or IGFBP-3 response to GH. The GHI group had a significantly reduced IGFBP-3 response to stimulation with 4 d of GH (median percent increment in IGFBP-3, 26%, versus 72% in the GHD group, P = 0.03); their IGF-I response to GH was also reduced (median % increment in IGF-I 75% versus 144% in the GH deficient group), but this did not achieve significance, p = 0.06. In all children, the percentage rise or delta SDS in both IGF-I and IGFBP-3 inversely correlated with the GH peak obtained on provocation testing, the latter being the most significant determinant of GH peak. We propose that the "IGF generation test", in particular IGFBP-3 generation, can be used in the investigation of partial GH insensitivity. Further work, however, is required to establish diagnostic criteria for partial GH insensitivity.
生长激素不敏感可能是一种遗传性疾病，也可能是营养不良性疾病的结果。拉伦综合征是生长激素不敏感最严重的形式，由生长激素受体缺失或缺陷引起。然而，可能存在不太严重的生长激素不敏感形式，导致身材矮小，但很少有拉伦综合征的其他特征。我们已经确定了一组身材矮小的异质性儿童，他们在生长激素激发试验中基础生长激素水平高（>10 mU/L）或峰值生长激素水平高（>40 mU/L），以检查生长激素敏感性的生化标志物。这些儿童接受了4天的生长激素（0.1 U/kg）治疗，并测定了胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白（BP）-3和生长激素结合蛋白（GHBP）的增量。八名开始生长激素治疗的生长激素缺乏症儿童被招募为阳性对照。两组在年龄、身高标准差评分（SDS）、身高增长速度SDS或体重指数方面无法区分。所有儿童的IGF-I和IGFBP-3生成均呈相关（IGF-I的SDS变化与IGFBP-3的SDS变化，r = 0.49，p = 0.03）。基础GHBP水平或GHBP的增量均不能预测IGF-I或IGFBP-3对生长激素的反应。生长激素不敏感（GHI）组对4天生长激素刺激的IGFBP-3反应明显降低（IGFBP-3的中位增量百分比为26%，而生长激素缺乏症（GHD）组为72%，P = 0.03）；他们对生长激素的IGF-I反应也降低了（IGF-I的中位增量百分比为75%，而生长激素缺乏组为144%），但未达到显著水平，p = 0.06。在所有儿童中，IGF-I和IGFBP-3的升高百分比或SDS变化与激发试验中获得的生长激素峰值呈负相关，后者是生长激素峰值的最主要决定因素。我们建议，“IGF生成试验”，特别是IGFBP-3生成试验，可用于部分生长激素不敏感的研究。然而，需要进一步的工作来建立部分生长激素不敏感的诊断标准。
