特异性结合蛋白对总甲状腺激素、游离甲状腺激素及皮质醇免疫测定的影响。

The effect of specific binding proteins on immunoassay measurements of total and free thyroid hormones and cortisol.

作者信息

Gant Kanegusuku Anastasia, Araque Katherine A, Nguyen Hung, Wei Bin, Hosseini Saman, Soldin Steven J

机构信息

Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.

Endocrinology Pituitary Institute, Pacific Neuroscience Institute, John Wayne Cancer Institute, Santa Monica, CA, USA.

出版信息

Ther Adv Endocrinol Metab. 2021 Jan 27;12:2042018821989240. doi: 10.1177/2042018821989240. eCollection 2021.

DOI:10.1177/2042018821989240

PMID:33552466

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7844449/

Abstract

BACKGROUND

Immunoassay (IA) measurements of thyroid hormones have previously given inaccurate results of triiodothyronine (T3), free triiodothyronine (FT3), and free thyroxine (FT4) when concentrations of TBG are low. We evaluate the hypothesis that abnormal concentrations of specific binding proteins (BPs) affect IA measurements and provide results which might misguide the diagnosis and treatment of patients. This study assesses IAs for the measurement of T3, FT3, and cortisol when levels of TBG and CBG are high or low. Comparisons are made between IA and LC-MS/MS.

METHODS

Serum or plasma samples with high (>95th percentile, = 25) or low (<5th percentile, = 27) concentrations of BP were collected. The concentrations of T3, FT3, and cortisol were measured by validated IA and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Spearman correlation and Wilcoxon matched-pairs signed rank analyses were used to compare the two methods.

RESULTS

When TBG levels are <5th percentile, the differences between the IA and LC-MS/MS results for T3 and FT3 are statistically significant (T3, = 0.0011; FT3, = 0.0003). When CBG levels are >95th percentile, the difference between the IA and LC-MS/MS measurements of cortisol is statistically significant ( = <0.0001).

CONCLUSION

Abnormal BP concentrations appear to affect the accuracy of IA measurements of T3, FT3, and cortisol. The population of patients with either high or low levels of BPs is significant. Our samples reflect that 65% of women aged between 15 and 49 years are taking oral contraceptives in the US, and thus have elevated levels of BPs. In this group, IA results for cortisol are falsely low. Our samples reflect that patients with protein losing diseases have low BP concentrations. Among a group with renal complications, IA measurements of T3 are overestimated, while those of FT3 are underestimated. Are the Food and Drug Administration and diagnostic companies adequately assessing the accuracy of IA tests?

摘要

背景

当甲状腺素结合球蛋白（TBG）浓度较低时，免疫分析法（IA）测定甲状腺激素的三碘甲状腺原氨酸（T3）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）的结果先前已被证明不准确。我们评估特定结合蛋白（BP）浓度异常会影响IA测定并提供可能误导患者诊断和治疗结果的这一假设。本研究评估当TBG和皮质类固醇结合球蛋白（CBG）水平高或低时，IA法测定T3、FT3和皮质醇的情况。对IA法和液相色谱-串联质谱法（LC-MS/MS）进行比较。

方法

收集BP浓度高（>第95百分位数，n = 25）或低（<第5百分位数，n = 27）的血清或血浆样本。采用经过验证的IA法和液相色谱串联质谱（LC-MS/MS）法测定T3、FT3和皮质醇的浓度。使用Spearman相关性分析和Wilcoxon配对符号秩分析来比较这两种方法。

结果

当TBG水平<第5百分位数时，IA法和LC-MS/MS法测定T3和FT3结果之间的差异具有统计学意义（T3，P = 0.0011；FT3，P = 0.0003）。当CBG水平>第95百分位数时，IA法和LC-MS/MS法测定皮质醇结果之间的差异具有统计学意义（P = <0.0001）。

结论

BP浓度异常似乎会影响IA法测定T3、FT3和皮质醇的准确性。BP水平高或低的患者群体数量可观。我们的样本显示，在美国，15至49岁的女性中有65%正在服用口服避孕药，因此其BP水平升高。在这组人群中，IA法测定皮质醇的结果会错误地偏低。我们的样本显示，患有蛋白质丢失性疾病的患者BP浓度较低。在一组有肾脏并发症的患者中，IA法测定T3的结果被高估，而FT3的结果被低估。美国食品药品监督管理局和诊断公司是否充分评估了IA检测的准确性？