Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Graeme Eisenhofer - , Institute of Clinical Chemistry and Laboratory Medicine, Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Peter Lattke - , University Hospital Carl Gustav Carus Dresden, Institute for Clinical Chemistry and Laboratory Medicine (Author)
  • Maria Herberg - , University Hospital Carl Gustav Carus Dresden, Institute for Medical Informatics and Biometry (Author)
  • Gabriele Siegert - , University Hospital Carl Gustav Carus Dresden, Institute for Clinical Chemistry and Laboratory Medicine (Author)
  • Nan Qin - , University Hospital Carl Gustav Carus Dresden, Institute for Clinical Chemistry and Laboratory Medicine (Author)
  • Roland Därr - , University Hospital Carl Gustav Carus Dresden, Department of Internal Medicine 3 (Author)
  • Jana Hoyer - , Max Planck Institute for Human Cognitive and Brain Sciences (Author)
  • Arno Villringer - , Max Planck Institute for Human Cognitive and Brain Sciences (Author)
  • Aleksander Prejbisz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Andrzej Januszewicz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Alan Remaley - , Eunice Kennedy Shriver National Institute of Child Health and Human Development (Author)
  • Victoria Martucci - , Eunice Kennedy Shriver National Institute of Child Health and Human Development (Author)
  • Karel Pacak - , Eunice Kennedy Shriver National Institute of Child Health and Human Development (Author)
  • H. Alec Ross - , Radboud University Nijmegen (Author)
  • Fred C.G.J. Sweep - , Radboud University Nijmegen (Author)
  • Jacques W.M. Lenders - , Radboud University Nijmegen (Author)

Abstract

Background: Measurements of plasma normetanephrine and metanephrine provide a useful diagnostic test for phaeochro-mocytoma, but this depends on appropriate reference intervals. Upper cut-offs set too high compromise diagnostic sensi-tivity, whereas set too low, false-positives are a problem. This study aimed to establish optimal reference intervals for plasma normetanephrine and metanephrine. Methods: Blood samples were collected in the supine position from 1226 subjects, aged 5-84 y, including 116 children, 575 normotensive and hypertensive adults and 535 patients in whom phaeochromocytoma was ruled out. Reference intervals were examined according to age and gender. Various models were examined to optimize upper cut-offs according to esti-mates of diagnostic sensitivity and specificity in a separate validation group of 3888 patients tested for phaeochromocytoma, including 558 with confirmed disease. Results: Plasma metanephrine, but not normetanephrine, was higher (P, 0.001) in men than in women, but reference inter-vals did not differ. Age showed a positive relationship (P, 0.0001) with plasma normetanephrine and a weaker relationship (P = 0.021) with metanephrine. Upper cut-offs of reference intervals for normetanephrine increased from 0.47 nmol/L in children to 1.05 nmol/L in subjects over 60 y. A curvilinear model for age-adjusted compared with fixed upper cut-offs for normetanephrine, together with a higher cut-off for metanephrine (0.45 versus 0.32 nmol/L), resulted in a substantial gain in diagnostic specificity from 88.3% to 96.0% with minimal loss in diagnostic sensitivity from 93.9% to 93.6%. Conclusions: These data establish age-adjusted cut-offs of reference intervals for plasma normetanephrine and optimized cut-offs for metanephrine useful for minimizing false-positive results.

Details

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalAnnals of clinical biochemistry
Volume50
Issue number1
Publication statusPublished - Jan 2013
Peer-reviewedYes

External IDs

PubMed 23065528

Keywords

ASJC Scopus subject areas