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

Eisenhofer, G., Lattke, P., Herberg, M., Siegert, G., Qin, N., Därr, R., et al. (2013). Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma. Annals of Clinical Biochemistry, 50(1), 62-69. doi:10.1258/acb.2012.012066.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-86DC-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-84FF-9
Genre: Journal Article

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 Creators:
Eisenhofer, Graeme1, 2, Author
Lattke, Peter1, Author
Herberg, Maria3, Author
Siegert, Gabriele1, Author
Qin, Nan1, Author
Därr, Roland2, Author
Hoyer, Jana4, Author              
Villringer, Arno4, Author              
Prejbisz, Aleksander5, Author
Januszewicz, Andrzej5, Author
Remaley, Alan6, Author
Martucci, Victoria7, Author
Pacak, Karel7, Author
Ross, Alec H.8, Author
Sweep, Fred C. G. J.8, Author
Lenders, Jacques W. M.9, Author
Affiliations:
1Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden, Germany, ou_persistent22              
2Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany, ou_persistent22              
3Institute for Medical Informatics and Biometry, University Hospital Carl Gustav Carus, Dresden, Germany, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
5Department of Hypertension, Institute of Cardiology, Warsaw, Poland, ou_persistent22              
6Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA, ou_persistent22              
7Program in Reproductive and Adult Endocrinology, National Institutes of Health, Bethesda, MD, USA, ou_persistent22              
8Department of Laboratory Medicine, Radboud University, Nijmegen, the Netherlands, ou_persistent22              
9Department of Internal Medicine, Radboud University, Nijmegen, the Netherlands, ou_persistent22              

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 Abstract: Background Measurements of plasma normetanephrine and metanephrine provide a useful diagnostic test for phaeochromocytoma, but this depends on appropriate reference intervals. Upper cut-offs set too high compromise diagnostic sensitivity, 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 estimates 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 intervals 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.

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Language(s): eng - English
 Dates: 2012-04-232012-10-122013-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1258/acb.2012.012066
PMID: 23065528
PMC: PMC4714582
Other: Epub 2012
 Degree: -

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Title: Annals of Clinical Biochemistry
  Abbreviation : Ann Clin Biochem
Source Genre: Journal
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Publ. Info: London, UK : Association of Clinical Biochemists
Pages: - Volume / Issue: 50 (1) Sequence Number: - Start / End Page: 62 - 69 Identifier: Other: 0004-5632
CoNE: https://pure.mpg.de/cone/journals/resource/0004-5632