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Eur J Endocrinol. 2015 Mar;172(3):251-60. doi: 10.1530/EJE-14-0730. Epub 2014 Dec 1.

Measurements of plasma metanephrines by immunoassay vs liquid chromatography with tandem mass spectrometry for diagnosis of pheochromocytoma.

Author information

1
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
2
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.

Abstract

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.

PMID:
25452465
DOI:
10.1530/EJE-14-0730
[Indexed for MEDLINE]
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