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

Graeme Eisenhofer, 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, Mercedes Robledo

Journal: Clinical chemistry and laboratory medicine 2021;59(2):353-363

PMID: 33001846

Free Full Text on Zurich Open Access Repository and Archive View on PubMed

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.

Address: Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; First Department of Medicine, University Medical Center Schleswig-Holstein, Lübeck, Germany.; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.; Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.; Department of Endocrinology, Diabetology and Clinical Nutrition, UniviersitätsSpital Zürich, Zurich, Switzerland.; Department of Computing and Information, University of Melbourne, MelbourneAustralia.; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.; Central Laboratory, University Hospital Würzburg, Würzburg, Germany.; Department of Hypertension, Institute of Cardiology, Warsaw, Poland.; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.

DOI: 10.1515/cclm-2020-0904

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https://doi.org/10.5167/uzh-200067

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MeSH Terms: Adrenal Gland Neoplasms, Adult, Aged, Aged, 80 and over, Algorithms, Biomarkers, Tumor, Dopamine, Female, Humans, Male, Metanephrine, Middle Aged, Mutation, Neurofibromatosis 1, Normetanephrine, Paraganglioma, Pheochromocytoma, Prospective Studies, Proto-Oncogenes, Risk Factors