Measurements of Plasma-Free Metanephrines by Immunoassay Versus Urinary Metanephrines and Catecholamines by Liquid Chromatography with Amperometric Detection for the Diagnosis of Pheochromocytoma/Paraganglioma

Abstract

Studies conflict concerning the use of enzyme immunoassays (EIA) for plasma free metanephrines (P-MNs) vs. other methods for pheochromocytoma/paraganglioma (PPGL) diagnosis. We compared commercially available EIAs for P-MNs with high-pressure liquid chromatography (HPLC) for 24 h-urinary MNs (U-MNs) and -catecholamines (U-CATs). 943 (565 female, 378 male) patients (54 PPGL, 889 Non-PPGL) were studied. Simultaneous measurements of all parameters analyzed at the central lab of our university hospital was mandatory for inclusion. Sensitivity of P-MNs (94.4%) was similar to that of U-MNs (100%), and both were higher than of U-CATs (77.8%), specificity of P-MNs (100%) higher than of U-MNs (73.6%), and similar to U-CATs (99.8%). With the recently proposed downward adjusted ULN of P-MNs to correct for the reported negative bias of the EIAs sensitivity (98.1%) raised non-significantly, but specificity decreased significantly (94.8%). Areas under receiver-operating characteristic curves indicated comparable diagnostic performance of P-MNs (0.989) vs. U-MNs (0.995), both better than U-CATs (0.956). In summary, the EIAs to measure P-MNs performed similarly to U-MNs by HPLC, and both better than U-CATs by HPLC. The post-test probability of PPGL given a positive test result was best for P-MNs, and higher than for the other pairs of analytes. Downward corrections of ULN of P-MNs did not improve test performances.

Pheochromocytomas and paragangliomas

“…Measurements of plasma free metanephrines and urinary fractionated metanephrines are currently considered standard of care [8]. A recent study compared urine and plasma metanephrines by both HPLC and enzyme immunoassay (EIA) methods and found that all four methods are of similar diagnostic utilities, in fact plasma metanephrines by EIA actually had the highest posttest probability in this analysis [13 ▪ ]. In the pediatric population, particular attention must be paid to the logistics of obtaining plasma and urine samples.…”

ProSAAS peptide of the granin protein family in biochemical diagnostics of pheochromocytoma

“…Currently, the most sensitive methods are chromatographic techniques, especially the technique of mass spectrometry (LC-MS/MS, liquid chromatography with tandem mass spectrometry). The sensitivity and specificity of this method in the determination of plasma free metanephrines is 94% and 100%, respectively [7]. In our work, we used the isotope method (RIA, radioimmunoassay) to determine plasma concentrations of metanephrine and normetanephrine.…”