title: Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytoma.
abstract: BACKGROUND
  The initial diagnosis of pheochromocytoma relies on plasma fractionated metanephrines levels. Normal levels exclude pheochromocytoma, but positive tests have a low positive predictive value due to the disease's rarity.
  
  
  OBJECTIVE
  The objective of the study was to evaluate three approaches to distinguish between true-positive and false-positive tests: 1) increased cutoff for plasma fractionated metanephrines, 2) measurement of serum/plasma chromogranin A (CGA), and 3) urine fractionated metanephrine testing.
  
  
  METHODS
  We studied retrospectively all Mayo Clinic patients with positive plasma fractionated metanephrine tests over a 15-month period and determined their final diagnosis based on histology, imaging, additional biochemical tests, and more than 1 yr follow-up. For a subgroup, urine fractionated metanephrine results were available. All original plasma samples were retested for CGA.
  
  
  RESULTS
  Of 140 patients, 40 had a chromaffin tumor confirmed and 100 excluded, indicating a positive predictive value of plasma fractionated metanephrines of 28.6%. Increasing the threshold for a positive test improved specificity to 98% but missed eight cases (20%). Incorporation of urine fractionated metanephrine testing as follow-up test achieved 80% specificity and 91% sensitivity. The corresponding figures for CGA were 71 and 87% for all patients and 89 and 87% when patients taking proton pump inhibitors were excluded.
  
  
  CONCLUSIONS
  Unless plasma fractionated metanephrines levels are elevated more than 4-fold above the upper limit of normal, patients with a positive plasma fractionated metanephrines test should be evaluated with urine fractionated metanephrines and serum/plasma CGA assays before being subjected to imaging or invasive diagnostic tests.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Algeciras-Schimnich
authors.forename: Carol M
authors.initials: CM
authors.lastname: Preissner
authors.forename: William F
authors.initials: WF
authors.lastname: Young
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.forename: Stefan K G
authors.initials: SK
authors.lastname: Grebe
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood* / Q000652:urine*; D053379:Chromogranin A / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood* / Q000652:urine*; D008875:Middle Aged; D008910:Minnesota; D010673:Pheochromocytoma / Q000097:blood* / Q000652:urine*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D053379:Chromogranin A; D008676:Metanephrine