Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients

Abstract

abstract. Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

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

“…In our study, specificity of measurements of plasma-free MNs exceeded that of the 24 urinary-fractionated MNs and does not support their contention. Our findings are in line with some [ 17 , 38 , 39 , 40 , 41 , 42 ] but not all [ 30 , 43 , 44 ] authors assessing the performance of P-MNs measured by EIA, and is not related to sample size nor to pre-TP of PPGL of the study populations ( Supplementary Figures S2 and S4 , respectively). Supplementary Figure S3 gives a summary of the diagnostic performance of the EIAs of the available literature for the quantification of plasma-free metanephrines.…”

“…However, PPGL not discovered are potentially life-threatening [ 12 , 13 , 48 ], and suspicion of PPGL given a positive biochemical test result may always be prudent. Six of the pertinent studies assessing P-MNs by EIA in comparison to other methods do not mention a FU of their patients defined free of PPGL [ 30 , 40 , 42 , 43 , 44 ], or do not report the duration of FU [ 38 ]. Three other series provide clinical, or clinical and radiological FU for 1–2 years [ 17 , 38 , 41 ] which is in line with our approach ( Supplementary Figure S4 ).…”

Diagnostic accuracy of plasma free metanephrines in a seated position compared with 24-hour urinary metanephrines in the investigation of pheochromocytoma

“…Whether this requirement is feasible for every patient at every center remains questionable. The clinical utility of plasma free metanephrines as a diagnostic for pheochromocytomas in Asian patients was lately evaluated by Tanaka et al [12], but the plasma free metanephrines were determined using an enzyme immunoassay. Unfortunately, such procedures can be susceptible to non-specific binding and cross-reactivity leading to lower diagnostic sensitivity and specificity compared to the liquid chromatography-tandem mass spectrometry (LC-MS/MS) which is known a reliable and sensitive test for the biochemical detection of pheochromocytoma [13].…”

Clinical evaluation and treatment of phaeochromocytoma

“…33 Several studies have demonstrated that plasma and urinary O-methylated catecholamine metabolites, normetadrenaline (NMA) and metadrenaline (MA) have high diagnostic sensitivity and specificity, which is essential for the biochemical diagnosis of PPGL (Table 2). [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] While there have been differences observed in the diagnostic sensitivity and specificity of UMets and PMets using different analytical methodologies, to date, there has not been a multicentre comparison using the gold standard method 1 of liquid chromatography tandem mass spectrometry (LC-MS/MS) for analysis.…”