{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:11:11Z","timestamp":1792858271190,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["314061271-CRC\/TRR 205\/1"],"award-info":[{"award-number":["314061271-CRC\/TRR 205\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Plasma-free normetanephrine and metanephrine (metanephrines) are the recommended biomarkers for testing of pheochromocytoma and paraganglioma (PPGL). This study evaluated the status of harmonization of liquid chromatography-tandem mass spectrometry-based measurements of plasma metanephrines and methoxytyramine and clinical interpretation of test results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>125 plasma samples from patients tested for PPGLs were analyzed in 12 laboratories. Analytical performance was also assessed from results of a proficiency-testing program. Agreement of test results from different laboratories was assessed by Passing-Bablok regression and Bland-Altman analysis. Agreement in clinical test interpretation based on laboratory specific reference intervals was also examined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Comparisons of analytical test results by regression analysis revealed strong correlations for normetanephrine and metanephrine (R\u2009\u2265\u20090.95) with mean slopes of 1.013 (range 0.975\u20131.078), and 1.019 (range 0.963\u20131.081), and intercepts of \u22120.584 (\u221253.736 to 54.790) and \u22123.194 (\u221217.152 to 5.933), respectively. The mean bias between methods was 1.2% (\u221211.6% to 16.0%) for metanephrine and 0.1% (\u221218.0% to 9.5%) for normetanephrine. Measurements of 3-methoxytyramine revealed suboptimal agreement between laboratories with biases ranging from \u221232.2% to 64.0%. Interrater agreement in test interpretation was &amp;gt;94% for metanephrine and &amp;gt;84% for normetanephrine; improvements in interrater agreement were observed with use of harmonized reference intervals, including age-specific cut-offs for normetanephrine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Analytical methods for metanephrines are well harmonized between laboratories. However, the 16% disagreement in test interpretation for normetanephrine suggests use of suboptimal method-dependent reference intervals for clinical decision-making for this metabolite. Improved analytical methods and reference interval harmonization are particularly required for 3-methoxytyramine.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvab060","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T19:54:19Z","timestamp":1618257259000},"page":"1098-1112","source":"Crossref","is-referenced-by-count":30,"title":["Harmonization of LC-MS\/MS Measurements of Plasma Free Normetanephrine, Metanephrine, and 3-Methoxytyramine"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-675X","authenticated-orcid":false,"given":"Mirko","family":"Peitzsch","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia","family":"Novos","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, New South Wales Health Pathology, Prince of Wales Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Kaden","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Kurlbaum","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology, Julius-Maximilians-Universit\u00e4t Wuerzburg, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius E","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Adaway","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Grouzmann","sequence":"additional","affiliation":[{"name":"D\u00e9partement M\u00e9decine de Laboratoire et Pathologie, Laboratoire des Cat\u00e9cholamines et Peptides, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"McWhinney","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Hoad","sequence":"additional","affiliation":[{"name":"PathWest Laboratory, Fiona Stanley Hospital, Perth, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Woollard","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Auckland City Hospital, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Centre Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Boot","sequence":"additional","affiliation":[{"name":"Department of Blood Sciences, Newcastle upon Tyne Hospitals NHS Foundation 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