免疫测定法与液相色谱-串联质谱法测定血浆甲氧基肾上腺素用于嗜铬细胞瘤的诊断。
Measurements of plasma metanephrines by immunoassay vs liquid chromatography with tandem mass spectrometry for diagnosis of pheochromocytoma.
机构信息
Endocrine and Diabetes UnitDepartment of Internal Medicine I, University Hospital, University of Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, GermanyComprehensive Heart Failure CenterUniversity of Würzburg, Würzburg, GermanyInstitute of Clinical Chemistry and Laboratory MedicineUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of HypertensionInstitute of Cardiology, Warsaw, PolandMedizinische Klinik und Poliklinik IVLudwig-Maximilians-Universität München, Munich, GermanyDivision for Specific EndocrinologyDepartment of Endocrinology and Diabetology, Medical Faculty, University Dusseldorf, Dusseldorf, GermanyLDN Labor Diagnostika Nord GmbH und Co. KGNordhorn, GermanyCentral Laboratory of the University Hospital of WuerzburgWürzburg, GermanyComprehensive Cancer Center MainfrankenUniversity of Würzburg, Würzburg, GermanyDepartment of Medicine IIIUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Endocrine and Diabetes UnitDepartment of Internal Medicine I, University Hospital, University of Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, GermanyComprehensive Heart Failure CenterUniversity of Würzburg, Würzburg, GermanyInstitute of Clinical Chemistry and Laboratory MedicineUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of HypertensionInstitute of Cardiology, Warsaw, PolandMedizinische Klinik und Poliklinik IVLudwig-Maximilians-Universität München, Munich, GermanyDivision for Specific EndocrinologyDepartment of Endocrinology and Diabetology, Medical Faculty, University Dusseldorf, Dusseldorf, GermanyLDN Labor Diagnostika Nord GmbH und Co. KGNordhorn, GermanyCentral Laboratory of the University Hospital of WuerzburgWürzburg, GermanyComprehensive Cancer Center MainfrankenUniversity of Würzburg, Würzburg, GermanyDepartment of Medicine IIIUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresd
Endocrine and Diabetes UnitDepartment of Internal Medicine I, University Hospital, University of Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, GermanyComprehensive Heart Failure CenterUniversity of Würzburg, Würzburg, GermanyInstitute of Clinical Chemistry and Laboratory MedicineUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of HypertensionInstitute of Cardiology, Warsaw, PolandMedizinische Klinik und Poliklinik IVLudwig-Maximilians-Universität München, Munich, GermanyDivision for Specific EndocrinologyDepartment of Endocrinology and Diabetology, Medical Faculty, University Dusseldorf, Dusseldorf, GermanyLDN Labor Diagnostika Nord GmbH und Co. KGNordhorn, GermanyCentral Laboratory of the University Hospital of WuerzburgWürzburg, GermanyComprehensive Cancer Center MainfrankenUniversity of Würzburg, Würzburg, GermanyDepartment of Medicine IIIUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
出版信息
Eur J Endocrinol. 2015 Mar;172(3):251-60. doi: 10.1530/EJE-14-0730. Epub 2014 Dec 1.
BACKGROUND
Reports conflict concerning measurements of plasma metanephrines (MNs) for diagnosis of pheochromocytomas/paragangliomas (PPGLs) by immunoassays compared with other methods. We aimed to compare the performance of a commercially available enzyme-linked immunoassay (EIA) kit with liquid chromatography-tandem mass spectrometric (LC-MS/MS) measurements of MNs to diagnose PPGLs.
METHODS
In a substudy of a prospective, multicenter trial to study the biochemical profiles of monoamine-producing tumors, we included 341 patients (174 males and 167 females) with suspected PPGLs (median age 54 years), of whom 54 had confirmed PPGLs. Plasma MNs were measured by EIA and LC-MS/MS, each in a specialized laboratory.
RESULTS
Plasma normetanephrine (NMN) and MN were measured 60 and 39% lower by EIA than by LC-MS/MS. Using upper cut-offs stipulated for the EIA, diagnostic sensitivity was only 74.1% at a specificity of 99.3%. In contrast, use of similar cut-offs for MN and overall lower age-adjusted cut-offs for NMN measured by LC-MS/MS returned a diagnostic sensitivity and specificity of 98.1 and 99.7%. Areas under receiver-operating characteristic curves, nevertheless, indicated comparable diagnostic performance of the EIA (0.993) and LC-MS/MS (0.985). Diagnostic sensitivity for the EIA increased to 96.2% with a minimal loss in specificity (95.1%) following use of cut-offs for the EIA adapted to correct for the negative bias.
CONCLUSIONS
The EIA underestimates plasma MNs and diagnostic sensitivity is poor using commonly stipulated cut-offs, resulting in a high risk for missing patients with PPGLs. Correction of this shortcoming can be achieved by appropriately determined cut-offs resulting in comparable diagnostic performance of EIA and LC-MS/MS assays.
背景
免疫测定法与其他方法相比，在用于诊断嗜铬细胞瘤/副神经节瘤（PPGL）的血浆代谢正肾上腺素（MNs）测量方面，报告结果存在冲突。我们旨在比较商业上可用的酶联免疫吸附测定（EIA）试剂盒与 MNs 的液相色谱-串联质谱（LC-MS/MS）测量，以诊断 PPGL。
方法
在一项前瞻性、多中心研究中，我们对单胺产生肿瘤的生化特征进行了亚研究，纳入了 341 名疑似患有 PPGL（中位年龄 54 岁，男性 174 名，女性 167 名）的患者，其中 54 名患者被确诊为 PPGL。血浆 MNs 通过专门的实验室分别采用 EIA 和 LC-MS/MS 进行测量。
结果
EIA 比 LC-MS/MS 测量的血浆去甲肾上腺素（NMN）和 MN 分别低 60%和 39%。使用 EIA 规定的上限切点，特异性为 99.3%时，诊断敏感性仅为 74.1%。相比之下，使用 LC-MS/MS 测量的 MN 和总体上较低的年龄调整后 NMN 切点，得到了 98.1%的诊断敏感性和 99.7%的特异性。然而，接受者操作特征曲线下面积表明 EIA（0.993）和 LC-MS/MS（0.985）的诊断性能相当。使用适应于纠正负偏倚的 EIA 切点，诊断敏感性增加至 96.2%，特异性损失最小（95.1%）。
结论
EIA 低估了血浆 MNs，使用常用规定的切点，诊断敏感性较差，导致 PPGL 患者漏诊的风险较高。通过适当确定切点来纠正这一缺陷，可以实现 EIA 和 LC-MS/MS 检测的诊断性能相当。
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