Multicenter Study on the Diagnostic Value of a New RIA for the Detection of Free Plasma Metanephrines in the Work‐Up for Pheochromocytoma

Abstract

Available laboratory test methods for the detection of elevated concentrations of catecholamines and their metabolites in urine and/or plasma are not always sensitive enough for the detection of pheochromocytoma. High-quality immunoassays for these compounds appear to be as accurate as high-pressure liquid chromatography (HPLC) or gas chromatography/mass spectrometry (GC-MS). Therefore, the current project aims to establish a new sensitive radioimmunoassay (RIA) for the measurement of free metanephrines in the plasma of patients in the work-up for pheochromocytoma. We report first results of an ongoing multicenter clinico-chemical evaluation study in hypertensive patients and normotensive volunteers. After an overnight fast plasma samples were collected on ice in EDTA- and heparin-coated tubes after insertion of an indwelling venous line and resting in the supine (patients) or sitting position (normal volunteers) for 30 min. Plasma metanephrines were measured by a newly developed RIA from IBL, Hamburg, Germany. Good agreement of the assay with the tandem mass spectrometry (LC-MS/MS) method for normetanephrine (r2=0.975) and for metanephrine (r2=0.985) could be demonstrated. Both specimens, EDTA and heparin plasma, can be used with the same results. The RIA has a good precision of <15% in the normal range and of <10% in the elevated concentration range. Our preliminary data suggest a high validity of the newly developed RIA for measuring free metanephrine and normetanephrine in hypertensive subjects in both EDTA and heparin plasma. Further work is required to determine the accuracy of the test in larger patient populations and in patients with pheochromocytoma.

The role of liquid chromatography–tandem mass spectrometry in the clinical laboratory

“…However, data interpretation may be complicated because of co-eluting compounds, and improvements can be made in reducing labour-intensive sample cleanup and total analysis time. Alternatively, rapid measurement of plasma free metanephrine can be achieved by the use of immunoassays [90,91]; however, cross-reactivity and nonspecific binding may lead to erroneous results. In addition, the lack of an internal standard in such assays reduces confidence in reported values.…”

Plasma Free Metanephrine Measurement Using Automated Online Solid-Phase Extraction HPLC–Tandem Mass Spectrometry

“…However, data interpretation may be complicated because of coeluting interference, and improvements can be made in reducing labor-intensive sample cleanup and total analysis time. Alternatively, rapid measurement of plasma free MN can be achieved by the use of immunoassays (14,15 ); however, cross-reactivity and nonspecific binding may lead to erroneous results. In addition, the lack of an internal standard in such assays reduces confidence in reported values.…”

Pilot quality assurance programme for plasma metanephrines

“…As a consequence, the numbers of centres measuring plasma metanephrines are still limited. Current methods include high pressure liquid chromatography (HPLC) with coulometric detection (CD), 7 immunoassay 8,9 and liquid chromatography-tandem mass spectroscopy (LC-MS/MS).…”