Objective

The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature.

Design

Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis.

Results

All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups.

Conclusion

Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

中文翻译：

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胰岛素样生长因子三元复合物成分作为诊断矮小症的生物标志物

客观的

儿童生长激素缺乏症 (GHD) 的诊断并不总是简单的，因为胰岛素样生长因子 1 (IGF-I) 或 GH 刺激试验可能无法区分 GHD 与体质性生长和青春期延迟 (CDGP) 或其他身材矮小的原因。

设计

因身材矮小就读于我科的男孩和女孩（n = 429, 0.7-16 岁）参加了这项研究。他们的平均随访时间为 9 年。在达到最终高度后的随访结束时，确定诊断，并确定三元复合物（IGF-I、IGF-结合蛋白-3（IGFBP-3）、酸不稳定亚基（ALS））的所有成分和 IGF-I/IGFBP-3 比率）被评估为各自诊断的生物标志物。

结果

三元复合体的所有成分相互之间密切相关，并且与年龄呈正相关。GHD 组和正常组之间的 IGF-I、IGFBP-3、ALS 和 IGF-I/IGFBP-3 比率有显着差异。与家族性身材矮小儿童相比，GHD 患者的 IGF-I 和 ALS 水平较低，而 GHD 患者的 IGF-I 和 IGF-I/IGFBP-3 比值显着低于 CDGP 儿童。IGF-I 和 IGF-I/IGFBP-3 受试者工作曲线截止点无法区分 GHD 和正常组或 GHD 和 CDGP 组。

结论

尽管三元复合体的所有成分之间密切相关，但每个成分都显示出统计学上显着的诊断依赖性改变。IGF-I、ALS、IGF-I/IGFBP-3比值在区分GHD与CDGP或GHD与正常组之间有优势，但没有可用的鉴别力，使生长发育学成为确立诊断的主要标准。