Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement

David Taïeb¹, Svenja Nölting^{2

3}, Nancy D Perrier⁴, Martin Fassnacht⁵, Jorge A Carrasquillo⁶, Ashley B Grossman^{7

8}, Roderick Clifton-Bligh⁹, George B Wanna¹⁰, Zachary G Schwam¹⁰, Laurence Amar^{11

12}, Isabelle Bourdeau¹³, Ruth T Casey¹⁴, Joakim Crona¹⁵, Cheri L Deal¹⁶, Jaydira Del Rivero¹⁷, Quan-Yang Duh¹⁸, Graeme Eisenhofer¹⁹, Tito Fojo^{20

21}, Hans K Ghayee^{22

23}, Anne-Paule Gimenez-Roqueplo^{11

24}, Antony J Gill^{25

26}, Rodney Hicks²⁷, Alessio Imperiale²⁸, Abhishek Jha²⁹, Michiel N Kerstens³⁰, Ronald R de Krijger^{31

32}, André Lacroix³³, Ivica Lazurova³⁴, Frank I Lin³⁵, Charlotte Lussey-Lepoutre^{11

36}, Eamonn R Maher¹⁴, Ozgur Mete³⁷, Mitsuhide Naruse^{38

39}, Naris Nilubol⁴⁰, Mercedes Robledo^{41

42}, Frédéric Sebag⁴³, Nalini S Shah⁴⁴, Akiyo Tanabe⁴⁵, Geoffrey B Thompson⁴⁶, Henri J L M Timmers⁴⁷, Jiri Widimsky⁴⁸, William J Young Jr⁴⁹, Leah Meuter⁵⁰, Jacques W M Lenders⁴⁷, Karel Pacak⁵¹

Affiliations

¹ Department of Nuclear Medicine, Aix-Marseille University, La Timone University Hospital, Marseille, France.
² Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
³ Department of Medicine IV, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
⁴ Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
⁶ Molecular Imaging and Therapy Service, Radiology Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ Green Templeton College, University of Oxford, Oxford, UK.
⁸ NET Unit, Royal Free Hospital, London, UK.
⁹ Department of Endocrinology, Royal North Shore Hospital and Cancer Genetics Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Université Paris Cité, Inserm, PARCC, Equipe Labellisée par la Ligue contre le Cancer, Paris, France.
¹² Hypertension Unit, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹³ Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.
¹⁴ Department of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
¹⁵ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁶ Research Center, CHU Sainte-Justine and Dept. of Paediatrics, University of Montreal, Montreal, Québec, Canada.
¹⁷ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁸ Department of Surgery, UCSF-Mount Zion, San Francisco, CA, USA.
¹⁹ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.
²⁰ Columbia University Irving Medical Center, New York City, NY, USA.
²¹ James J. Peters VA Medical Center, New York City, NY, USA.
²² Division of Endocrinology & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA.
²³ Malcom Randall VA Medical Center, Gainesville, FL, USA.
²⁴ Department of Oncogenetics and Cancer Genomic Medicine, AP-HP, Hôpital européen Georges Pompidou, Paris, France.
²⁵ University of Sydney, Sydney NSW Australia, Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
²⁶ NSW Health Pathology Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
²⁷ Department of Medicine, St Vincent's Hospital Medical School, Melbourne, Victoria, Australia.
²⁸ Department of Nuclear Medicine and Molecular Imaging - Institut de Cancérologie de Strasbourg Europe (ICANS), IPHC, UMR 7178, CNRS, University of Strasbourg, Strasbourg, France.
²⁹ Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
³⁰ Department of Endocrinology, University Medical Center Groningen, Groningen, Netherlands.
³¹ Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
³² Princess Máxima Center for paediatric oncology, Utrecht, Netherlands.
³³ Division of Endocrinology, Department of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Canada.
³⁴ Department of Internal Medicine 1, University Hospital, P.J. Šafárik University, Košice, Slovakia.
³⁵ Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁶ Sorbonne University, Department of Nuclear Medicine, Pitié-Salpêtrière, Paris, France.
³⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
³⁸ Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center and Endocrine Center, Kyoto, Japan.
³⁹ Clinical Research Center, Ijinkai Takeda General Hospital, Kyoto, Japan.
⁴⁰ Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁴¹ Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
⁴² Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain.
⁴³ Department of Endocrine Surgery, Aix-Marseille University, Conception Hospital, Marseille, France.
⁴⁴ Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India.
⁴⁵ Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo, Japan.
⁴⁶ Division of Endocrine Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
⁴⁷ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
⁴⁸ Third Department of Medicine, Department of Endocrinology and Metabolism of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁴⁹ Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.
⁵⁰ Stanford University School of Medicine, Department of Physician Assistant Studies, Stanford, CA, USA.
⁵¹ Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. karel@mail.nih.gov.

PMID: 38097671
DOI: 10.1038/s41574-023-00926-0

Review

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement

David Taïeb et al. Nat Rev Endocrinol. 2024 Mar.

. 2024 Mar;20(3):168-184.

doi: 10.1038/s41574-023-00926-0. Epub 2023 Dec 14.

Authors

Affiliations

¹ Department of Nuclear Medicine, Aix-Marseille University, La Timone University Hospital, Marseille, France.
² Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
³ Department of Medicine IV, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
⁴ Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
⁶ Molecular Imaging and Therapy Service, Radiology Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ Green Templeton College, University of Oxford, Oxford, UK.
⁸ NET Unit, Royal Free Hospital, London, UK.
⁹ Department of Endocrinology, Royal North Shore Hospital and Cancer Genetics Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Université Paris Cité, Inserm, PARCC, Equipe Labellisée par la Ligue contre le Cancer, Paris, France.
¹² Hypertension Unit, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹³ Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.
¹⁴ Department of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
¹⁵ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁶ Research Center, CHU Sainte-Justine and Dept. of Paediatrics, University of Montreal, Montreal, Québec, Canada.
¹⁷ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁸ Department of Surgery, UCSF-Mount Zion, San Francisco, CA, USA.
¹⁹ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.
²⁰ Columbia University Irving Medical Center, New York City, NY, USA.
²¹ James J. Peters VA Medical Center, New York City, NY, USA.
²² Division of Endocrinology & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA.
²³ Malcom Randall VA Medical Center, Gainesville, FL, USA.
²⁴ Department of Oncogenetics and Cancer Genomic Medicine, AP-HP, Hôpital européen Georges Pompidou, Paris, France.
²⁵ University of Sydney, Sydney NSW Australia, Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
²⁶ NSW Health Pathology Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
²⁷ Department of Medicine, St Vincent's Hospital Medical School, Melbourne, Victoria, Australia.
²⁸ Department of Nuclear Medicine and Molecular Imaging - Institut de Cancérologie de Strasbourg Europe (ICANS), IPHC, UMR 7178, CNRS, University of Strasbourg, Strasbourg, France.
²⁹ Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
³⁰ Department of Endocrinology, University Medical Center Groningen, Groningen, Netherlands.
³¹ Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
³² Princess Máxima Center for paediatric oncology, Utrecht, Netherlands.
³³ Division of Endocrinology, Department of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Canada.
³⁴ Department of Internal Medicine 1, University Hospital, P.J. Šafárik University, Košice, Slovakia.
³⁵ Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁶ Sorbonne University, Department of Nuclear Medicine, Pitié-Salpêtrière, Paris, France.
³⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
³⁸ Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center and Endocrine Center, Kyoto, Japan.
³⁹ Clinical Research Center, Ijinkai Takeda General Hospital, Kyoto, Japan.
⁴⁰ Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁴¹ Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
⁴² Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain.
⁴³ Department of Endocrine Surgery, Aix-Marseille University, Conception Hospital, Marseille, France.
⁴⁴ Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India.
⁴⁵ Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo, Japan.
⁴⁶ Division of Endocrine Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
⁴⁷ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
⁴⁸ Third Department of Medicine, Department of Endocrinology and Metabolism of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁴⁹ Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.
⁵⁰ Stanford University School of Medicine, Department of Physician Assistant Studies, Stanford, CA, USA.
⁵¹ Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. karel@mail.nih.gov.

PMID: 38097671
DOI: 10.1038/s41574-023-00926-0

Abstract

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

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References

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Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement

Affiliations

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Research Materials