Growth hormone assays: current methodologies and their limitations

Growth hormone assays: current methodologies and their limitations
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DOI:
10.1007/s11102-007-0030-1
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发表时间:
2007-06-01
期刊:
影响因子:
3.8
通讯作者:
Strasburger, Christian J.
Strasburger, Christian J.
中科院分区:
医学2区
文献类型:
--
作者:
Bidlingmaier, Martin;Strasburger, Christian J.

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测量循环生长激素 (GH) 浓度对于诊断 GH 缺乏或 GH 过量至关重要。用于测量肽激素的免疫测定法的发明是一项重大突破,使得能够对更大系列样品中的 GH 浓度进行常规分析。在过去的几十年中,测量技术已经从灵敏度较低、主要基于多克隆抗血清的放射性测定发展到最新一代采用单克隆抗体的高灵敏度化学发光方法。不幸的是,新测定的开发并没有导致不同测定方法获得的结果之间更好的一致性。相反,当基于单克隆抗体的检测变得更加流行时,差异往往会增加。特定患者样本中 GH 浓度的实际报告值仍然主要取决于各自实验室使用的方法,限制了国际共识指南在临床实践中的适用性。分析物本身的异质性、用于校准的不同参比制剂的可用性以及 GH 结合蛋白等基质成分的干扰是 GH 测定标准化困难的原因之一。另一个挑战来自于治疗肢端肥大症的 GH 受体拮抗剂的可用性,肢端肥大症基本上是 GH 的突变形式,因此会干扰许多 GH 测定。本综述概述了临床实践中使用的 GH 检测方法、其局限性以及标准化的下一步可能采取的措施。
Measurement of circulating growth hormone (GH) concentrations is essential in diagnosis of either GH deficiency or GH excess. The invention of immunoassays for the measurement of peptide hormones was a major breakthrough, enabling the routine analysis of GH concentrations in larger series of samples. Over the last few decades, measurement technology has evolved from less sensitive, mainly radioactive assays based on polyclonal antisera to the latest generations of highly sensitive chemiluminescence methods employing monoclonal antibodies. Unfortunately, the development of newer assays did not lead to better agreement among the results obtained by different assay methods. On the contrary, the differences tended to increase when monoclonal antibody based assays became more popular. The actual value reported for the GH concentration in a specific patient's sample still mainly depends on the method used by the respective laboratory, limiting the applicability of international consensus guidelines in clinical practice. The heterogeneity of the analyte itself, the availability of different reference preparations for calibration and the interference from matrix components such as GH binding protein are among the reasons why standardizing GH assays is difficult. An additional challenge arose from the availability of a GH receptor antagonist for the treatment of acromegaly, which is basically a mutated form of GH and therefore interferes in many GH assays. This review provides an overview on GH assays used in clinical practice, their limitations and the potential next steps towards standardization.