Spencer C A, Bergoglio L M, Kazarosyan M, Fatemi S, LoPresti J S
Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
J Clin Endocrinol Metab. 2005 Oct;90(10):5566-75. doi: 10.1210/jc.2005-0671. Epub 2005 Jun 28.
Changes in thyroglobulin (Tg) and/or Tg antibody (TgAb) methods can disrupt the serial monitoring of differentiated thyroid carcinoma (DTC) patients.
This study compared Tg measurements made in TgAb-negative and TgAb-positive sera using four RIA and 10 immunometric assay (IMA) methods.
TgAb detection using a panel of 12 direct methods was contrasted with four Tg recovery tests. Sera from 110 normal euthyroid subjects (68 TgAb negative/42 TgAb positive) and 131 TgAb-negative DTC patients had Tg and/or TgAb analyses made by 10 laboratories in four countries. Euthyroid controls were used to compare Tg and TgAb ranges, sensitivities, and TgAb interference, whereas DTC patients were used to study Tg assay specificities, hook effects, and the influence of high Tg levels on TgAb measurements.
Tg methods had high between-method variability [47 +/- 3% (+/-sem)] that was only marginally reduced by CRM-457 standardization (37 +/- 3%). All methods had suboptimal sensitivity, and some failed to detect Tg in some normal euthyroid controls. Although direct TgAb measurements were more reliable than exogenous recovery tests, TgAb status was only concordant in 65% of sera. Only four of 42 (9.5%) sera containing TgAb had antibody detected by all direct methods. All IMA methods reported paradoxically undetectable Tg for many TgAb-positive euthyroid controls, suggesting TgAb interference, whereas RIA methods reported appropriate normal range values for these same subjects. Some sera displaying interference had TgAb detected by only a minority of methods.
Specificity differences, suboptimal sensitivity, hook effects, and an inability to reliably detect interfering TgAb compromise the clinical utility of current Tg and TgAb methods. All of the IMA methods were prone to underestimate serum Tg in the presence of TgAb, whereas the RIA methods appeared resistant to TgAb interference.
甲状腺球蛋白（Tg）和/或Tg抗体（TgAb）检测方法的改变可能会干扰分化型甲状腺癌（DTC）患者的连续监测。
本研究比较了使用四种放射免疫分析（RIA）和十种免疫分析（IMA）方法对TgAb阴性和TgAb阳性血清中Tg的检测结果。
使用一组12种直接检测方法检测TgAb，并与四种Tg回收率检测进行对比。来自110名甲状腺功能正常的受试者（68名TgAb阴性/42名TgAb阳性）和131名TgAb阴性的DTC患者的血清，由四个国家的10个实验室进行Tg和/或TgAb分析。甲状腺功能正常的对照用于比较Tg和TgAb的范围、灵敏度以及TgAb干扰情况，而DTC患者则用于研究Tg检测的特异性、钩状效应以及高Tg水平对TgAb检测的影响。
Tg检测方法之间的差异很大[47±3%（±标准误）]，通过CRM-457标准化后仅略有降低（37±3%）。所有方法的灵敏度都不理想，有些方法未能在一些甲状腺功能正常的对照中检测到Tg。虽然直接检测TgAb比外源性回收率检测更可靠，但TgAb状态在65%的血清中才一致。42份（9.5%）含有TgAb的血清中，只有4份血清的抗体能被所有直接检测方法检测到。所有IMA方法均报告许多TgAb阳性的甲状腺功能正常对照的Tg检测不到，提示存在TgAb干扰，而RIA方法对这些相同受试者报告的是适宜的正常范围值。一些显示干扰的血清中，TgAb仅被少数方法检测到。
特异性差异、灵敏度不理想、钩状效应以及无法可靠检测干扰性TgAb，损害了当前Tg和TgAb检测方法的临床实用性。所有IMA方法在存在TgAb时都容易低估血清Tg，而RIA方法似乎对TgAb干扰有抗性。
