Kristiansen Søren, Friis-Hansen Lennart
a Department of Clinical Biochemistry, North Zealand Hospital , University of Copenhagen , Hilleroed , Denmark.
Scand J Clin Lab Invest. 2019 Feb-Apr;79(1-2):43-49. doi: 10.1080/00365513.2019.1571624. Epub 2019 Feb 19.
Standardization programs for thyroid hormones have revealed bias between immunochemical methods and the reference method ED-ID-LC/MS. Lack of standardization between methods, suboptimal reference intervals and replacement of serum with plasma may compromise the capability of the immunochemical thyroid methods to diagnose thyroid disease. To accommodate the demand for faster turn-around times for laboratory replies, we replaced serum with plasma on some serum CE marked thyroid methods. This forced us to do on-board analytical correction for the plasma total T4 (TT4) method on ADVIA Centaur XP. We, next, validated the capability of the ADVIA Centaur XP thyroid methods on plasma by (1) first carrying out a prospective method comparison with the ED-ID-LC/MS reference method using collected plasma samples, (2) we verified the clinical reference intervals by analyzing collected plasma samples from healthy individuals, and (3) retrospectively compared laboratory results from two different time periods using serum TT4 and serum total triiodothyronine (TT3) versus plasma free thyroxine (FT4) and plasma TT3, respectively, to diagnose thyroid disease. The plasma FT4 method displayed a negative concentration-dependent bias against the reference method. This bias was apparently counteracted by a fitted reference interval for the plasma FT4 method. Indeed, overt hyperthyroid disease was found in 1.0% and 1.1% of the cases using serum and plasma and overt hypothyroid condition were in 1.3% and 0.6% of the cases using serum and plasma, respectively. In conclusion, the ADVIA Centaur XP FT4 method displayed a negative bias at high plasma FT4 concentrations against the reference method, but the diagnostic performance was not compromised due to a fitted reference interval.
甲状腺激素标准化项目已揭示免疫化学方法与参考方法电喷雾电离串联液相色谱/质谱法（ED-ID-LC/MS）之间存在偏差。方法之间缺乏标准化、参考区间不理想以及用血浆替代血清可能会影响免疫化学甲状腺方法诊断甲状腺疾病的能力。为了满足实验室更快回复周转时间的需求，我们在一些血清CE标记的甲状腺方法中用血浆替代了血清。这迫使我们对ADVIA Centaur XP上的血浆总T4（TT4）方法进行机载分析校正。接下来，我们通过以下方式验证了ADVIA Centaur XP甲状腺方法在血浆上的性能：（1）首先使用收集的血浆样本与ED-ID-LC/MS参考方法进行前瞻性方法比较；（2）通过分析健康个体收集的血浆样本验证临床参考区间；（3）回顾性比较两个不同时间段分别使用血清TT4和血清总三碘甲状腺原氨酸（TT3）与血浆游离甲状腺素（FT4）和血浆TT3诊断甲状腺疾病的实验室结果。血浆FT4方法相对于参考方法表现出负的浓度依赖性偏差。这种偏差显然被血浆FT4方法的拟合参考区间抵消。实际上，使用血清和血浆时，分别在1.0%和1.1%的病例中发现明显的甲状腺功能亢进疾病，在使用血清和血浆时，分别在1.3%和0.6%的病例中发现明显的甲状腺功能减退情况。总之，ADVIA Centaur XP FT方法在高血浆FT4浓度下相对于参考方法表现出负偏差，但由于拟合的参考区间，诊断性能并未受到影响。
