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临床上甲状腺功能正常的患者 FT4 和 FT3 水平可疑升高:是临床发现还是分析陷阱?

Dubiously increased FT4 and FT3 levels in clinically euthyroid patients: clinical finding or analytical pitfall?

机构信息

Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, (ILM) Leipzig University, Leipzig, Germany.

pes Gesellschaft für medizinische Diagnosesysteme mbH, Markkleeberg, Germany.

出版信息

Clin Chem Lab Med. 2022 Feb 25;60(6):877-885. doi: 10.1515/cclm-2021-1211. Print 2022 May 25.

DOI:10.1515/cclm-2021-1211
PMID:35213944
Abstract

OBJECTIVES

We systematically investigated normally or subclinically increased thyroid stimulating hormone (TSH) values associated with unexpectedly increased thyroxine (FT4) and free triiodothyronine (FT3) in findings of patients without any thyroid disease. Moreover, we looked for alternatives to overcome such states with an improved diagnostic procedure and to investigate the pathogenetic background of the respective patients.

METHODS

Samples with TSH concentrations within the range of 0.4-10 mU/L combined with increased concentrations of FT4 (n=120; Cobas, Roche) were collected over a period of around six years. Cobas FT4 results were compared with measurements from Liaison (DiaSorin) and Architect (Abbott) FT4 assays. For further validation all samples were measured for total thyroxine (TT4) (Cobas, Roche). Finally, FT3 and TT3 as complementary parameters were measured in samples with leftover material. To overcome potential analytical disturbances from stimulating heterophilic antibodies, we used heterophilic blocking tubes (HBTs).

RESULTS

From the 120 samples with increased FT4 concentrations by Cobas, 51/120 were also increased by Liaison, and 26/120 by Architect. However, the measurement of TT4 indicated only n=10/120 increased values. The number of increased FT3 (n=71) measurements was higher in Architect>Cobas>Liaison (28>27>9). TT3 levels of 70/71 samples were within the reference interval. HBTs were inappropriate to reduce unspecific immunoreactivity in our samples. No clear pathogenetic background could be elucidated in the anamnesis of individual patients.

CONCLUSIONS

To overcome dubious constellations of TSH, FT4, and FT3, it is helpful to measure TT4 and TT3 for control or to use an immunoassay with an alternative assay design for the respective parameters.

摘要

目的

我们系统地研究了正常或亚临床甲状腺刺激激素(TSH)水平升高与甲状腺素(FT4)和游离三碘甲状腺原氨酸(FT3)水平意外升高相关的情况,这些情况出现在没有任何甲状腺疾病的患者中。此外,我们寻找替代方法来克服这种状态,改善诊断程序,并研究相应患者的发病机制背景。

方法

在大约六年的时间内,收集了 TSH 浓度在 0.4-10 mU/L 范围内且 FT4 浓度升高的样本(n=120;罗氏 Cobas)。罗氏 Cobas 的 FT4 结果与 Liaison(DiaSorin)和 Architect(Abbott)FT4 检测结果进行了比较。为了进一步验证,所有样本均用 Roche Cobas 测量总甲状腺素(TT4)。最后,在有剩余样本的情况下,测量 FT3 和 TT3 作为补充参数。为了克服潜在的分析干扰,如刺激异嗜性抗体,我们使用了异嗜性阻断管(HBT)。

结果

在 120 例 Cobas 检测到 FT4 浓度升高的样本中,51/120 例 Liaison 检测也升高,26/120 例 Architect 检测也升高。然而,用 TT4 测量时,仅 n=10/120 例升高。Architect>Cobas>Liaison(28>27>9)的 FT3 升高测量例数更多。70/71 例 TT3 水平在参考区间内。在我们的样本中,HBT 不适合减少非特异性免疫反应。在个别患者的病史中,无法明确阐明发病机制背景。

结论

为了克服 TSH、FT4 和 FT3 可疑的组合情况,测量 TT4 和 TT3 进行对照或使用具有替代检测设计的免疫测定法来测量相应参数是有帮助的。

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