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血清甲状腺球蛋白自身抗体:分化型甲状腺癌患者中的患病率、对血清甲状腺球蛋白测量的影响及预后意义

Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.

作者信息

Spencer C A, Takeuchi M, Kazarosyan M, Wang C C, Guttler R B, Singer P A, Fatemi S, LoPresti J S, Nicoloff J T

机构信息

Department of Medicine, University of Southern California, Los Angeles 90033, USA.

出版信息

J Clin Endocrinol Metab. 1998 Apr;83(4):1121-7. doi: 10.1210/jcem.83.4.4683.

DOI:10.1210/jcem.83.4.4683
PMID:9543128
Abstract

The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.

摘要

与普通人群相比,分化型甲状腺癌(DTC)患者循环甲状腺自身抗体(TgAb或抗甲状腺过氧化物酶)的患病率增加了近3倍(分别为40%和14%)。25%的DTC患者和10%的普通人群中存在血清TgAb(无论有无抗甲状腺过氧化物酶)。术后连续血清TgAb和血清Tg模式与疾病的存在与否相关。通过放射免疫分析(RIA)和两种免疫分析方法(IMA)对87份TgAb阳性血清进行血清Tg测量,以研究TgAb干扰情况。TgAb干扰定义为相对于TgAb阴性血清,Tg RIA和Tg IMA值之间存在显著的方法间不一致(变异系数>41.7%),在69%的TgAb阳性血清中发现了这种情况。TgAb干扰的特征是Tg RIA值高于IMA值,并且一般来说,在含有高浓度TgAb的血清中更频繁、更严重。然而,一些血清在血清TgAb水平较低(1 - 2 IU/mL)时显示出明显的干扰,而其他TgAb值非常高(>1000 IU/mL)的血清则没有干扰。发现凝集法对于检测导致干扰的低浓度TgAb(1 - 10 IU/mL)过于不敏感。外源性Tg回收率测试是检测TgAb干扰的不可靠方法。具体而言,回收的外源性Tg随添加的Tg类型和量以及孵育时间而变化。此外,对于一些显示出明显血清RIA/IMA不一致的血清,发现回收率超过80%。对于循环TgAb的DTC患者,血清Tg的测量目前存在问题。使用一种能够提供与肿瘤状态一致测量值的Tg检测方法很重要。当存在TgAb时,IMA方法容易低估血清Tg,增加漏诊持续性或转移性DTC的风险。本研究中使用的RIA方法在转移性DTC的TgAb阳性患者组中提供了更符合临床的血清Tg值。此外,由于连续血清TgAb测量与连续血清Tg RIA测量平行,TgAb浓度可能是随访TgAb阳性患者的另一个临床上有用的肿瘤标志物参数。连续血清Tg和TgAb测量之间的差异可能提醒医生注意TgAb干扰血清Tg测量的可能性,并促使在临床决策中更谨慎地使用此类数据。

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