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Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma

  • Graeme Eisenhofer ORCID logo EMAIL logo , Timo Deutschbein , Georgiana Constantinescu , Katharina Langton , Christina Pamporaki , Bruna Calsina , Maria Monteagudo , Mirko Peitzsch , Stephanie Fliedner , Henri J. L. M. Timmers , Nicole Bechmann , Maria Fankhauser , Svenja Nölting , Felix Beuschlein , Anthony Stell , Martin Fassnacht , Aleksander Prejbisz , Jacques W. M. Lenders and Mercedes Robledo
Published/Copyright: October 1, 2020
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 2

Abstract

Objectives

Plasma free metanephrines are commonly used for diagnosis of pheochromocytoma and paraganglioma (PPGLs), but can also provide other information. This multicenter study prospectively examined whether tumor size, location, and mutations could be predicted by these metabolites.

Methods

Predictions of tumor location, size, and mutation type, based on measurements of plasma normetanephrine, metanephrine, and methoxytyramine were made without knowledge of disease in 267 patients subsequently determined to have PPGLs.

Results

Predictions of adrenal vs. extra-adrenal locations according to increased plasma concentrations of metanephrine and methoxytyramine were correct in 93 and 97% of the respective 136 and 33 patients in who these predictions were possible. Predicted mean tumor diameters correlated positively (p<0.0001) with measured diameters; predictions agreed well for pheochromocytomas but were overestimated for paragangliomas. Considering only patients with mutations, 51 of the 54 (94%) patients with NF1 or RET mutations were correctly predicted with those mutations according to increased plasma metanephrine, whereas no or minimal increase in metanephrine correctly predicted all 71 patients with either VHL or SDHx mutations; furthermore, among the latter group increases in methoxytyramine correctly predicted SDHx mutations in 93% of the 29 cases for this specific prediction.

Conclusions

Extents and patterns of increased plasma O-methylated catecholamine metabolites among patients with PPGLs allow predictions of tumor size, adrenal vs. extra-adrenal locations and general types of mutations. Predictions of tumor location are, however, only possible for patients with clearly increased plasma methoxytyramine or metanephrine. Where possible or clinically relevant the predictions are potentially useful for subsequent clinical decision-making.

Keywords: gene mutations; metanephrines; paraganglioma; pheochromocytoma; tumor location
Corresponding author: Graeme Eisenhofer, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; and Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr.74, 01307 Dresden, Germany, Phone: +49 351 458 4595, Fax: +49 351 458 7346, E-mail:

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: CRC/TRR 205

Funding source: European Union Seventh Framework Programme - FP7/2007–2013

Award Identifier / Grant number: 259735 (ENS@T-Cancer)

  1. Research funding: This work was supported by the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement 259735 (ENS@T-Cancer) and the Deutsche Forschungsgemeinschaft (CRC/TRR 205).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study protocol was approved by the Ethics Committees of the participating centers.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0904).

Received: 2020-06-12
Accepted: 2020-09-14
Published Online: 2020-10-01
Published in Print: 2021-02-23

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2020-0904
Keywords for this article
gene mutations; metanephrines; paraganglioma; pheochromocytoma; tumor location

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Assuring the quality of examinations using faecal immunochemical tests for haemoglobin (FIT)
  4. Review
  5. Capillary electrophoresis based on nucleic acid analysis for diagnosing inherited diseases
  6. Mini Reviews
  7. Negative hair test result after long-term drug use. About a case involving morphine and literature review
  8. Prorenin and active renin levels in paediatrics: a bioanalytical review
  9. Opinion Paper
  10. From therapeutic drug monitoring to total drug monitoring and drug-omics
  11. Perspectives
  12. The internal quality control in the traceability era
  13. Genetics and Molecular Diagnostics
  14. External quality assessment (EQA) and alternative assessment procedures (AAPs) in molecular diagnostics: findings of an international survey
  15. General Clinical Chemistry and Laboratory Medicine
  16. An evaluation of ten external quality assurance scheme (EQAS) materials for the faecal immunochemical test (FIT) for haemoglobin
  17. Optimizing hepcidin measurement with a proficiency test framework and standardization improvement
  18. Development of a certified reference material for anti-β2-glycoprotein I IgG – commutability studies
  19. Influence of patients’ clinical features at intensive care unit admission on performance of cell cycle arrest biomarkers in predicting acute kidney injury
  20. Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1–3
  21. Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma
  22. Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma
  23. Reference Values and Biological Variations
  24. Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents
  25. Cardiovascular Diseases
  26. Comparison of acetylsalicylic acid and clopidogrel non-responsiveness assessed by light transmittance aggregometry and PFA-100® in patients undergoing neuroendovascular procedures
  27. Trimethylamine-N-oxide (TMAO) predicts short- and long-term mortality and poor neurological outcome in out-of-hospital cardiac arrest patients
  28. Non-lactate strong ion difference and cardiovascular, cancer and all-cause mortality
  29. Infectious Diseases
  30. Performance of three automated SARS-CoV-2 antibody assays and relevance of orthogonal testing algorithms
  31. Development, evaluation, and validation of machine learning models for COVID-19 detection based on routine blood tests
  32. Searching for a role of procalcitonin determination in COVID-19: a study on a selected cohort of hospitalized patients
  33. Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials
  34. Erratum
  35. Corrigendum to: The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
  36. Letter to the Editors
  37. Harmonization of antineutrophil cytoplasmic antibodies (ANCA) testing by reporting test result-specific likelihood ratios: position paper
  38. Independent internal quality control (IQC) for faecal immunochemical tests (FIT) for haemoglobin: use of FIT manufacturers’ IQC for other FIT systems
  39. Parallel testing of 241 clinical nasopharyngeal swabs for the detection of SARS-CoV-2 virus on the Cepheid Xpert Xpress SARS-CoV-2 and the Roche cobas SARS-CoV-2 assays
  40. Sustained SARS-CoV-2 nucleocapsid antibody levels in nonsevere COVID-19: a population-based study
  41. Evidence for increased circulating procoagulant phospholipids in patients with COVID-19 pneumonia and their prognostic role
  42. Complete blood counts and cell population data from Sysmex XN analyser in the detection of SARS-CoV-2 infection
  43. Macro creatine kinase in an asymptomatic patient: a case report
  44. Implementation of pre-labelled barcode tubes and the GeT-System in a general hospital for the exact documentation of the time of venous blood sample and improvement of sample quality
  45. Determination of free light chains: assay-dependent differences in interpretation
  46. Association between SOX17, Wif-1 and RASSF1A promoter methylation status and response to chemotherapy in patients with metastatic gastric cancer
  47. Effect of two organizational interventions on the frequency of haemoglobin A1c and erythrocyte sedimentation rate testing
  48. Haemoglobin A1c determination from dried blood spots prepared with HemaSpot™ blood collection devices: comparison with fresh capillary blood
  49. Stability of catecholamines in whole blood: influence of time between collection and centrifugation
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