Welsh Kerry J, Stolze Brian R, Yu Xiaolin, Podsiadlo Trisha R, Kim Lisa S, Soldin Steven J
Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States.
Clin Biochem. 2017 Apr;50(6):318-322. doi: 10.1016/j.clinbiochem.2016.11.022. Epub 2016 Nov 25.
Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology.
Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed.
Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7±5.0 medications, all factors known to interfere with results found on immunoassays.
Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.
非甲状腺疾病综合征患者的甲状腺激素检测存在许多异常。此类患者患有与血清蛋白水平低相关的内科合并症,且正在服用多种会干扰免疫分析平台对甲状腺激素测量的药物。目前尚不清楚这些甲状腺激素测量结果是反映生理状况,还是检测方法造成的假象。
从我们机构的重症监护病房(ICU)选取50例患者。采用金标准液相色谱-串联质谱法(LC-MSMS)测定血浆中的总甲状腺激素和游离甲状腺激素。将结果与罗氏Cobas 6000进行比较。评估患者的内科合并症和结合蛋白水平。
与免疫分析相比,LC-MSMS检测显示总三碘甲腺原氨酸(TT3)和总甲状腺素(TT4)浓度显著更易偏低。免疫分析和LC-MSMS检测的游离三碘甲腺原氨酸(FT3)水平相似。然而,通过超滤LC-MSMS检测时,许多患者的FT4浓度轻度升高(19/50,38%),而免疫分析时为1/50(2%)(p=0.0001)。白蛋白和甲状腺素结合球蛋白降低很常见,患者平均服用11.7±5.0种药物,所有这些因素均已知会干扰免疫分析结果。
参考LC-MSMS和常见免疫分析平台之间在甲状腺激素测量上存在明显差异。据推测,几种药物会取代T4与低亲和力白蛋白的结合,与免疫分析相比,通过LC-MSMS检测会使FT4浓度升高,且由于我们研究人群中结合蛋白水平低,免疫分析值会被错误降低。