从儿童期到青年期，胰岛素样生长因子（IGF）结合蛋白（IGFBP）-3评估在生长激素（GH）缺乏诊断中的准确性：与IGF-II的低GH依赖性及循环中IGFBP-3 18千道尔顿片段的存在相关。

Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment.

作者信息

Cianfarani Stefano, Liguori Alice, Boemi Sergio, Maghnie Mohamad, Iughetti Lorenzo, Wasniewska Malgorzata, Street Maria E, Zucchini Stefano, Aimaretti Gianluca, Germani Daniela

机构信息

Rina Balducci Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Room E-178, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy.

出版信息

J Clin Endocrinol Metab. 2005 Nov;90(11):6028-34. doi: 10.1210/jc.2005-0721. Epub 2005 Aug 9.

DOI:10.1210/jc.2005-0721

PMID:16091488

Abstract

CONTEXT

Poor sensitivity of IGF binding protein (IGFBP)-3 assessment in the work-up of GH deficiency (GHD) has been ascribed to the equal affinity of IGFBP-3 for IGF-I and IGF-II and to IGFBP-3 proteolysis.

OBJECTIVE

The objective of this study was to determine the IGF-II GH dependency and IGFBP-3 proteolysis in patients with GHD from childhood to young adulthood.

DESIGN

This study was cross-sectional.

SETTING

This was a national multicenter study performed in university hospitals.

PATIENTS

One hundred thirty-one subjects (chronological age, 1.3-25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were studied.

INTERVENTIONS

IGF-I, IGF-II, and IGFBP-3 serum concentrations were measured by immunoradiometric assay. IGFBP-3 circulating forms were assessed by Western immunoblot (WIB) analysis.

MAIN OUTCOME MEASURES

Main outcome measures were sensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements.

RESULTS

Sensitivity and specificity of IGFBP-3 measurement were 27 and 100%, respectively. IGFBP-3 sensitivity was 46% in young adulthood. Sensitivity and specificity of IGF-I were 69 and 81%, respectively. Sensitivity and specificity of IGF-II assessment were 23 and 97%, respectively. IGFBP-3 WIB revealed the presence of the intact form and the major 29-kDa fragment in both GHD and subjects with idiopathic short stature. In patients with GHD, WIB showed the presence of an additional smaller IGFBP-3 fragment migrating at approximately 18 kDa.

CONCLUSIONS

Our results suggest that in children and young adults with GHD, the low GH dependency of IGF-II together with IGFBP-3 proteolytic activity yielding the 18-kDa fragment concur to reduce the sensitivity of IGFBP-3 assessment, ultimately making it too inaccurate as a screening test in the work-up of GHD.

摘要

背景

胰岛素样生长因子结合蛋白（IGFBP）-3评估在生长激素缺乏症（GHD）检查中的敏感性较差，这归因于IGFBP-3对胰岛素样生长因子（IGF）-I和IGF-II的亲和力相同以及IGFBP-3的蛋白水解作用。

目的

本研究的目的是确定儿童至青年期GHD患者的IGF-II生长激素依赖性和IGFBP-3蛋白水解作用。

设计

本研究为横断面研究。

地点

这是一项在大学医院进行的全国多中心研究。

患者

研究了131名受试者（实际年龄1.3 - 25岁），其中72例GHD患者和59例特发性身材矮小受试者。

干预措施

采用免疫放射分析法测定血清IGF-I、IGF-II和IGFBP-3浓度。通过Western免疫印迹（WIB）分析评估IGFBP-3的循环形式。

主要观察指标

主要观察指标为IGF-I、IGF-II和IGFBP-3测量的敏感性和特异性。

结果

IGFBP-3测量的敏感性和特异性分别为27%和100%。青年期IGFBP-3的敏感性为46%。IGF-I的敏感性和特异性分别为69%和81%。IGF-II评估的敏感性和特异性分别为23%和97%。IGFBP-3的WIB显示，在GHD患者和特发性身材矮小受试者中均存在完整形式和主要的29 kDa片段。在GHD患者中，WIB显示存在另一个迁移约18 kDa的较小IGFBP-3片段。