血浆游离去甲变肾上腺素、变肾上腺素和 3-甲氧基酪胺的 LC-MS/MS 测量的协调。
Harmonization of LC-MS/MS Measurements of Plasma Free Normetanephrine, Metanephrine, and 3-Methoxytyramine.
机构信息
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Clinical Chemistry, New South Wales Health Pathology, Prince of Wales Hospital, Sydney, Australia.
出版信息
Clin Chem. 2021 Aug 5;67(8):1098-1112. doi: 10.1093/clinchem/hvab060.
BACKGROUND
Plasma-free normetanephrine and metanephrine (metanephrines) are the recommended biomarkers for testing of pheochromocytoma and paraganglioma (PPGL). This study evaluated the status of harmonization of liquid chromatography-tandem mass spectrometry-based measurements of plasma metanephrines and methoxytyramine and clinical interpretation of test results.
METHODS
125 plasma samples from patients tested for PPGLs were analyzed in 12 laboratories. Analytical performance was also assessed from results of a proficiency-testing program. Agreement of test results from different laboratories was assessed by Passing-Bablok regression and Bland-Altman analysis. Agreement in clinical test interpretation based on laboratory specific reference intervals was also examined.
RESULTS
Comparisons of analytical test results by regression analysis revealed strong correlations for normetanephrine and metanephrine (R ≥ 0.95) with mean slopes of 1.013 (range 0.975-1.078), and 1.019 (range 0.963-1.081), and intercepts of -0.584 (-53.736 to 54.790) and -3.194 (-17.152 to 5.933), respectively. The mean bias between methods was 1.2% (-11.6% to 16.0%) for metanephrine and 0.1% (-18.0% to 9.5%) for normetanephrine. Measurements of 3-methoxytyramine revealed suboptimal agreement between laboratories with biases ranging from -32.2% to 64.0%. Interrater agreement in test interpretation was >94% for metanephrine and >84% for normetanephrine; improvements in interrater agreement were observed with use of harmonized reference intervals, including age-specific cut-offs for normetanephrine.
CONCLUSIONS
Analytical methods for metanephrines are well harmonized between laboratories. However, the 16% disagreement in test interpretation for normetanephrine suggests use of suboptimal method-dependent reference intervals for clinical decision-making for this metabolite. Improved analytical methods and reference interval harmonization are particularly required for 3-methoxytyramine.
背景
游离去甲肾上腺素和甲氧基肾上腺素（甲氧基肾上腺素）是检测嗜铬细胞瘤和副神经节瘤（PPGL）的推荐生物标志物。本研究评估了基于液相色谱-串联质谱法测量血浆甲氧基肾上腺素和间羟酪氨酸的分析性能以及检测结果的临床解释的协调情况。
方法
对 125 例经检测患有 PPGL 的患者的血浆样本在 12 个实验室进行分析。还通过能力验证计划的结果评估了分析性能。通过 Passing-Bablok 回归和 Bland-Altman 分析评估了不同实验室的检测结果的一致性。还研究了基于实验室特定参考区间的临床检测解释的一致性。
结果
通过回归分析比较分析测试结果，发现去甲肾上腺素和甲氧基肾上腺素具有很强的相关性（R≥0.95），平均斜率分别为 1.013（范围 0.975-1.078）和 1.019（范围 0.963-1.081），截距分别为-0.584（-53.736 至 54.790）和-3.194（-17.152 至 5.933）。方法之间的平均偏差为甲氧基肾上腺素 1.2%（-11.6%至 16.0%），去甲肾上腺素 0.1%（-18.0%至 9.5%）。实验室之间的 3-甲氧基酪氨酸测量结果不一致，偏差范围为-32.2%至 64.0%。甲氧基肾上腺素和去甲肾上腺素的检测解释的组内一致性>94%和>84%；使用协调的参考区间，包括去甲肾上腺素的年龄特异性截止值，观察到组内一致性的提高。
结论
实验室之间的甲氧基肾上腺素分析方法很好地协调一致。然而，去甲肾上腺素的检测解释有 16%的不一致，这表明在临床决策中使用代谢物的方法依赖的参考区间并不理想。需要进一步改进分析方法和参考区间的协调，特别是对于 3-甲氧基酪氨酸。
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