Mauras N, Walton P, Nicar M, Welch S, Rogol A D
Nemours Children's Clinic and Research Programs, 807 Nira St., Jacksonville, Florida 32207, USA.
Pediatr Res. 2000 Nov;48(5):614-8. doi: 10.1203/00006450-200011000-00010.
Accurate interpretation of the results of GH stimulation tests is of pivotal importance not only in the evaluation of the etiology of growth retardation in children but also in the selection of the best candidates for GH therapy. We performed this study to test a novel immunofunctional GH ( IFGH) assay that makes use of the concept that one GH molecule dimerizes two GH receptors and compared the results with those obtained using two GH assays, the Diagnostic Systems Laboratories ELISA and a Hybritech immunoradiometric assay in 19 children with short stature undergoing routine GH stimulation testing. We also tested 13 normally statured control children to revisit the issue of what constitutes normal GH responses to stimuli, using all three assays and arginine and either L-dopa or insulin-induced hypoglycemia as secretagogues. Concentrations of IGF-I, IGF binding protein-3, and acid labile subunit were measured as well. There was a significant correlation between peak IFGH and Diagnostic Systems Laboratories ELISA GH responses to stimuli (r(2) = 0.93) as well as between the Diagnostic Systems Laboratories ELISA and Hybritech immunoradiometric assay (r(2) = 0.91). There were no significant differences between the short stature and normal group in peak or mean GH concentrations regardless of the assay used; however, the IGF-I, IGF binding protein-3, and acid labile subunit concentrations were substantially lower in the short stature group. There was a wide spectrum of GH concentrations in the normal group; approximately 50% of the children had peak GH concentrations <7 ng/mL, approximately 30% <5 ng/mL, and two pubertal normal subjects peaked to only 2 ng/mL with use of both the ELISA and IFGH assays. We conclude that 1) sensitive GH assays, ELISA and immunoradiometric assay, accurately detect a GH capable of generating a biologic signal comparable to an IFGH and 2) that normal GH stimulation test results can be substantially lower than previously accepted. GH-dependent growth factors may be more sensitive indicators of GH sufficiency than GH concentrations in response to pharmacologic stimuli.
准确解读生长激素（GH）刺激试验的结果不仅对评估儿童生长发育迟缓的病因至关重要，而且对选择生长激素治疗的最佳候选者也至关重要。我们开展这项研究，以测试一种新型免疫功能生长激素（IFGH）检测方法，该方法利用一个生长激素分子使两个生长激素受体二聚化的概念，并将结果与使用两种生长激素检测方法（诊断系统实验室酶联免疫吸附测定法（ELISA）和海布里奇免疫放射测定法）对19名身材矮小儿童进行常规生长激素刺激试验所获得的结果进行比较。我们还对13名身材正常的对照儿童进行了检测，使用这三种检测方法以及精氨酸和左旋多巴或胰岛素诱导的低血糖作为促分泌剂，以重新审视什么构成对刺激的正常生长激素反应这一问题。同时还测量了胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白-3（IGFBP-3）和酸性不稳定亚基的浓度。IFGH峰值与诊断系统实验室ELISA生长激素对刺激的反应之间存在显著相关性（r(2) = 0.93），诊断系统实验室ELISA与海布里奇免疫放射测定法之间也存在显著相关性（r(2) = 0.91）。无论使用何种检测方法，身材矮小组和正常组在生长激素峰值或平均浓度方面均无显著差异；然而，身材矮小组的IGF-I、IGFBP-3和酸性不稳定亚基浓度显著较低。正常组的生长激素浓度范围很广；使用ELISA和IFGH检测方法时，约50%的儿童生长激素峰值浓度<7 ng/mL，约30%<5 ng/mL，两名青春期正常受试者峰值仅为2 ng/mL。我们得出结论：1）灵敏的生长激素检测方法，即ELISA和免疫放射测定法，能够准确检测出一种能够产生与IFGH相当的生物信号的生长激素；2）正常的生长激素刺激试验结果可能比以前公认的要低得多。与对药物刺激的生长激素浓度相比，生长激素依赖性生长因子可能是生长激素充足性更敏感的指标。
