title: Plasma free metanephrine, normetanephrine, and 3-methoxytyramine for the diagnosis of pheochromocytoma/paraganglioma.
abstract: BACKGROUND
  Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL secrete either catecholamine or their metabolites, metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and metanephrine (MN) for the diagnosis of PHEO/PGL.
  
  
  METHODS
  Sixty-five patients referred to endocrine/ENT clinics were enrolled. Twelve patients with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients (39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14 patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age- and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN were measured using high-performance liquid chromatography. Receivers operating characteristics was plotted and cut-off levels were established.
  
  
  RESULTS
  When compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in 3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL, there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-, 6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in combination with MN was high in 97% of the patients with PHEO/PGL. All three metabolites in combination were high in 83% of patients with HNPGL. In malignant PHEO/PGL, 50% subjects had increased levels of both NM and 3MT.
  
  
  CONCLUSIONS
  Measurement of plasma-free NM along with 3MT and MN provides a better tool for the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT can be used for the diagnosis of malignant PHEO/PGL.
authors.affiliation: Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.
authors.forename: M L
authors.initials: ML
authors.lastname: Khurana
authors.affiliation: Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khadgawat
authors.affiliation: Department of Nuclear Medicine, AIIMS, New Delhi, India.
authors.forename: C S
authors.initials: CS
authors.lastname: Bal
authors.affiliation: Department of Biostatistics, AIIMS, New Delhi, India.
authors.forename: Guresh
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Department of E. N. T, AIIMS, New Delhi, India.
authors.forename: S C
authors.initials: SC
authors.lastname: Sharma
authors.affiliation: Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
keywords: 3 methoxy tyramine; metanephrine; normetanephrine; paraganglioma; pheochromocytoma