CONSENSUS DOCUMENTGenetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of HypertensionLenders, Jacques W.M.a,b; Kerstens, Michiel N.c; Amar, Laurenced; Prejbisz, Aleksandere; Robledo, Mercedesf; Taieb, Davidg; Pacak, Karelh; Crona, Joakimi; Zelinka, Tomášj; Mannelli, Massimok; Deutschbein, Timol; Timmers, Henri J.L.M.a; Castinetti, Fredericm; Dralle, Henningn; Widimský, Jřrij; Gimenez-Roqueplo, Anne-Pauleo; Eisenhofer, Graemeb,pAuthor Information aDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands bDepartment of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany cDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands dUnité d’Hypertension Artérielle, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université de Paris-PARCC, INSERM, Paris, France eDepartment of Hypertension, Institute of Cardiology, Warsaw, Poland fHereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain gDepartment of Nuclear Medicine, La Timone University Hospital, European Center for Research in Medical Imaging, Aix-Marseille University, Marseille, France hSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA iDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden jCenter for Hypertension, 3rd Department of Medicine, Division of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic kDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy lDivision of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany mAix-Marseille Université, Department of Endocrinology, Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille Medical Genetics (MMG), et Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France nDepartment of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University of Duisburg-Essen, Essen, Germany oAssistance Publique-Hôpitaux de Paris, AP-HP, Hôpital Européen Georges Pompidou, Service de Génétique, Université de Paris, PARCC, INSERM, Paris, France pInstitute of Clinical Chemistry and Laboratory Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany Correspondence to Jacques W.M. Lenders, MD, PhD, Radboud University Medical Center, Nijmegen, Department of Internal Medicine, P.O. Box 6500 HB, Geert Grooteplein Zuid 8, Nijmegen, 6525GA, The Netherlands. Tel: +31243618819; fax: +31243541734; e-mail: Jacques.firstname.lastname@example.org Abbreviations: 123I-MIBG, 123I-metaiodobenzylguanidine; 18F-FDOPA, 18F-fluorodihydroxy-phenylalanine; ATRX, alpha-thalassemia/mental retardation syndrome X-linked; BP, blood pressure; CSDE1, cold-shock domain containing E1; CT, computed tomography; HIF2α, hypoxia inducible factor 2α; HNPGL, head/neck paraganglioma; LC-ECD, liquid chromatography with electrochemical detection; LC-MS/MS, liquid chromatography with tandem mass spectrometry; MAML3, MAsterMind-Like 3; MAX MYC, associated factor X; MDH2, malate dehydrogenase 2; MEN2, multiple endocrine neoplasia type 2; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1; NGS, next-generation sequencing; PET, positron emission tomography; PGL, paraganglioma; PPGL, phaeochromocytoma and paraganglioma; RET, rearranged during transfection; SDHA, succinate dehydrogenase subunit A; SDHAF2, succinate dehydrogenase complex assembly factor 2; SDHB, succinate dehydrogenase subunit B; SDHC, succinate dehydrogenase subunit C; SDHD, succinate dehydrogenase subunit D; SLC25A11, solute carrier family 25 member 11; TCGA, the cancer genome atlas; TERT, telomerase reverse transcriptase; TMEM127, transmembrane domain protein 127; VHL, von Hippel-Lindau; VUS, variants of unknown significance Received 4 January, 2020 Revised 16 February, 2020 Accepted 27 February, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). Journal of Hypertension: August 2020 - Volume 38 - Issue 8 - p 1443-1456 doi: 10.1097/HJH.0000000000002438 Buy SDC Metrics Abstract Phaeochromocytoma and paraganglioma (PPGL) are chromaffin cell tumours that require timely diagnosis because of their potentially serious cardiovascular and sometimes life- threatening sequelae. Tremendous progress in biochemical testing, imaging, genetics and pathophysiological understanding of the tumours has far-reaching implications for physicians dealing with hypertension and more importantly affected patients. Because hypertension is a classical clinical clue for PPGL, physicians involved in hypertension care are those who are often the first to consider this diagnosis. However, there have been profound changes in how PPGLs are discovered; this is often now based on incidental findings of adrenal or other masses during imaging and increasingly during surveillance based on rapidly emerging new hereditary causes of PPGL. We therefore address the relevant genetic causes of PPGLs and outline how genetic testing can be incorporated within clinical care. In addition to conventional imaging (computed tomography, MRI), new functional imaging approaches are evaluated. The novel knowledge of genotype-phenotype relationships, linking distinct genetic causes of disease to clinical behaviour and biochemical phenotype, provides the rationale for patient-tailored strategies for diagnosis, follow-up and surveillance. Most appropriate preoperative evaluation and preparation of patients are reviewed, as is minimally invasive surgery. Finally, we discuss risk factors for developing metastatic disease and how they may facilitate personalised follow-up. Experts from the European Society of Hypertension have prepared this position document that summarizes the current knowledge in epidemiology, genetics, diagnosis, treatment and surveillance of PPGL. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.