Hauffa Berthold P, Lehmann Nils, Bettendorf Markus, Mehls Otto, Dörr Helmuth-Günther, Stahnke Nikolaus, Steinkamp Heinz, Said Elfriede, Ranke Michael B
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Heidelberg, Germany.
Eur J Endocrinol. 2007 Nov;157(5):597-603. doi: 10.1530/EJE-07-0338.
Childhood GH deficiency, suspected in the presence of decreased height velocity and short stature, is usually characterized by low IGF-I and IGF-binding protein-3 (IGFBP-3) serum concentrations and is conventionally confirmed by diminished GH peak responses to pharmacological stimuli.
We evaluated the agreement between different IGF-I (IGFBP-3) assays in predicting GH deficiency and tested whether variability between growth factor screening and pharmacological testing could be diminished by reassessment of growth factor and GH peak concentrations in a single laboratory.
Using the Tuebingen IGF-I (IGFBP-3) RIA, 317 (321) sera from children evaluated for growth disorders in 19 centers were reanalyzed. In 103 children with insulin hypoglycemia and arginine tests, we evaluated how the association between the outcome of growth factor screening and functional testing would change if different assays were employed.
Locally measured IGF-I correlated better than IGFBP-3 with the results of the central laboratory (Tuebingen) assay (slope of the regression curve 1.05; 95% confidence interval (95% CI) 1.01-1.1 versus 1.18; 95% CI 1.09-1.3). Agreement between local and central laboratory assays in predicting GH deficiency was better for IGF-I than for IGFBP-3 assays (kappa =0.59 versus kappa =0.47). The poor agreement between growth factor screening and GH pharmacological testing was not improved when hormone concentrations were remeasured in the central laboratory (kappa local=-0.0031, central=0.12).
In children with impaired growth, growth factor screening reflects different aspects of GH insufficiency than does functional testing. Agreement between these approaches is poor and could not be improved by reduction of assay-related variability.
儿童生长激素缺乏症,在身高增长速度减慢和身材矮小的情况下被怀疑,通常表现为血清胰岛素样生长因子-I(IGF-I)和胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度降低,传统上通过对药物刺激的生长激素峰值反应减弱来确诊。
我们评估了不同的IGF-I(IGFBP-3)检测方法在预测生长激素缺乏症方面的一致性,并测试了通过在单个实验室重新评估生长因子和生长激素峰值浓度,是否可以减少生长因子筛查和药物检测之间的变异性。
使用图宾根IGF-I(IGFBP-3)放射免疫分析,对来自19个中心评估生长障碍的儿童的317份(321份)血清进行重新分析。在103名接受胰岛素低血糖和精氨酸试验的儿童中,我们评估了如果采用不同的检测方法,生长因子筛查结果与功能测试之间的关联将如何变化。
本地测量的IGF-I与中心实验室(图宾根)检测结果的相关性优于IGFBP-3(回归曲线斜率1.05;95%置信区间(95%CI)1.01-1.1,而IGFBP-3为1.18;95%CI 1.09-1.3)。在预测生长激素缺乏症方面,本地实验室和中心实验室检测结果之间的一致性,IGF-I检测优于IGFBP-3检测(kappa值分别为0.59和0.47)。当在中心实验室重新测量激素浓度时,生长因子筛查与生长激素药物检测之间的一致性较差的情况并未得到改善(本地kappa值=-0.0031,中心kappa值=0.12)。
在生长受损的儿童中,生长因子筛查反映的生长激素不足的方面与功能测试不同。这些方法之间的一致性较差,且不能通过减少检测相关的变异性来改善。