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Measurements of Plasma Methoxytyramine, Normetanephrine, and Metanephrine as Discriminators of Different Hereditary Forms of Pheochromocytoma
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BACKGROUND: Pheochromocytomas are rare catecholamine-producing tumors derived in more than 30% of cases from mutations in 9 tumor-susceptibility genes identified to date, including von Hippel-Lindau tumor suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (SDHB); and succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD). Testing of multiple genes is often undertaken at considerable expense before a mutation is detected. This study assessed whether measurements of plasma metanephrine, normetanephrine, and methoxytyramine, the O-methylated metabolites of catecholamines, might help to distinguish different hereditary forms of the tumor. METHODS: Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD. RESULTS: In contrast to patients with VHL, SDHB, and SDHD mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDHB and SDHD mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL, SDHB, and SDHD gene mutations in 99% of cases by the combination of normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDHB and SDHD mutations from those with VHL mutations in an additional 78% of cases. CONCLUSIONS: The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily used tool to guide cost-effective genotyping of underlying disease-causing mutations.
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“Additionally, measurements of plasma methoxytyramine discriminated patients with SDH mutations from those with VHL mutations in a further 78% of cases (181).”
From Adrenal incidentaloma (2020) · cites this paper as [181]
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“In 1 large study of patients with pheochromocytoma and/or paraganglioma, patients with NF1 and MEN2 mutations could be discriminated from those with VHL and SDH mutations in 99% of cases by the relative concentrations of normetanephrine and metanephrine, as all patients with NF1 and MEN2 presented with tumors characterized by increased plasma concentrations of metanephrine, in contrast to patients”
From Adrenal incidentaloma (2020) · cites this paper as [181]
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Metadata
- Authors
- Eisenhofer, G., Lenders, J. W., Timmers, H., Mannelli, M., Grebe, S. K., Hofbauer, L. C., Bornstein, S. R., Tiebel, O., Adams, K., Bratslavsky, G., Linehan, W. M., & Pacak, K.
- Affiliations
- Technische Universität Dresden (DE)
- Radboud University Nijmegen (NL)
- University of Florence (IT)
- Mayo Clinic (US)
- Institute of Clinical Chemistry and Laboratory Medicine and
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- National Institutes of Health (US)
- Reproductive and Adult Endocrinology Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
- Corresponding author
- Eisenhofer, Graeme
- ORCID
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-01
- Volume
- 57
- Issue
- 3
- Pages
- 411-420
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC3164998
- OpenAlex
- W2163960412
- Cited by
- 290
- References
- 35
- Citations by year
- 2025: 6 · 2024: 6 · 2023: 15 · 2022: 16 · 2021: 20 · 2020: 16 · 2019: 16 · 2018: 17 · 2017: 32 · 2016: 19 · 2015: 32 · 2014: 31 · 2013: 27 · 2012: 22
- FWCI
- 30.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Deutsche Forschungsgesellschaft
- Center for Regenerative Therapies Dresden
- Dresden Tumor Center
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Center for Cancer Research
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- pheochromocytoma, familial pheochromocytoma, methoxytyramine, normetanephrine, metanephrine, von Hippel-Lindau disease, SDHB mutation, SDHD mutation, multiple endocrine neoplasia type 2, neurofibromatosis type 1, genotyping, epinephrine, norepinephrine, dopamine
- MeSH terms
- Adrenal Gland Neoplasms, Diagnosis, Differential, Dopamine, Humans, Metanephrine, Neoplastic Syndromes, Hereditary, Normetanephrine, Pheochromocytoma, Retrospective Studies, Biomarkers, Tumor
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