This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Algeciras-Schimnich, A. Articles by Grebe, S. K. G. Search for Related Content PubMed PubMed Citation Articles by Algeciras-Schimnich, A. Articles by Grebe, S. K. G. Related Collections Adrenal and Hypertension Cardiovascular Endocrinology Endocrine Oncology

Plasma Chromogranin A or Urine Fractionated Metanephrines Follow-Up Testing Improves the Diagnostic Accuracy of Plasma Fractionated Metanephrines for Pheochromocytoma

Departments of Laboratory Medicine and Pathology (A.A.-S., C.M.P., R.J.S., S.K.G.G.) and Medicine (W.F.Y., S.K.G.G.), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Stefan K. G. Grebe, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905. E-mail: grebs{at}mayo.edu.

Context: 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.

Objectives: 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.

Design: 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.