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

Endocr J. 2014;61(7):667-73. doi: 10.1507/endocrj.ej13-0277. Epub 2014 May 28.


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.

Publication types

  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Adrenal Gland Neoplasms / blood
  • Adrenal Gland Neoplasms / diagnosis*
  • Adrenal Gland Neoplasms / pathology
  • Adrenal Gland Neoplasms / urine
  • Adrenal Glands / pathology
  • Adult
  • Biomarkers / blood
  • Biomarkers / chemistry
  • Biomarkers / urine
  • Cohort Studies
  • Female
  • Hospitals, Municipal
  • Hospitals, University
  • Humans
  • Immunoenzyme Techniques
  • Japan
  • Male
  • Metanephrine / blood*
  • Metanephrine / chemistry
  • Metanephrine / urine
  • Middle Aged
  • Normetanephrine / blood*
  • Normetanephrine / chemistry
  • Normetanephrine / urine
  • Pheochromocytoma / blood
  • Pheochromocytoma / diagnosis*
  • Pheochromocytoma / pathology
  • Pheochromocytoma / urine
  • Prospective Studies
  • Sensitivity and Specificity
  • Solubility
  • Vanilmandelic Acid / urine


  • Biomarkers
  • Normetanephrine
  • Metanephrine
  • Vanilmandelic Acid