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

David Taïeb; Svenja Nölting; Nancy D Perrier; Martin Fassnacht; Jorge A Carrasquillo; Ashley B Grossman; Roderick Clifton-Bligh; George B Wanna; Zachary G Schwam; Laurence Amar; Isabelle Bourdeau; Ruth T Casey; Joakim Crona; Cheri L Deal; Jaydira Del Rivero; Quan-Yang Duh; Graeme Eisenhofer; Tito Fojo; Hans K Ghayee; Anne-Paule Gimenez-Roqueplo; Antony J Gill; Rodney Hicks; Alessio Imperiale; Abhishek Jha; Michiel N Kerstens; Ronald R de Krijger; André Lacroix; Ivica Lazurova; Frank I Lin; Charlotte Lussey-Lepoutre; Eamonn R Maher; Ozgur Mete; Mitsuhide Naruse; Naris Nilubol; Mercedes Robledo; Frédéric Sebag; Nalini S Shah; Akiyo Tanabe; Geoffrey B Thompson; Henri J L M Timmers; Jiri Widimsky; William J Young; Leah Meuter; Jacques W M Lenders; Karel Pacak

doi:10.1038/s41574-023-00926-0

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

David Taïeb
, Svenja Nölting
, Nancy D Perrier
, Martin Fassnacht
, Jorge A Carrasquillo
, Ashley B Grossman
, Roderick Clifton-Bligh
, George B Wanna
, Zachary G Schwam
, Laurence Amar
, Isabelle Bourdeau
, Ruth T Casey
, Joakim Crona
, Cheri L Deal
, Jaydira Del Rivero
, Quan-Yang Duh
, Graeme Eisenhofer
, Tito Fojo
, Hans K Ghayee
, Anne-Paule Gimenez-Roqueplo

Antony J Gill, Rodney Hicks, Alessio Imperiale, Abhishek Jha, Michiel N Kerstens, Ronald R de Krijger, André Lacroix, Ivica Lazurova, Frank I Lin, Charlotte Lussey-Lepoutre, Eamonn R Maher, Ozgur Mete, Mitsuhide Naruse, Naris Nilubol, Mercedes Robledo, Frédéric Sebag, Nalini S Shah, Akiyo Tanabe, Geoffrey B Thompson, Henri J L M Timmers, Jiri Widimsky, William J Young, Leah Meuter, Jacques W M Lenders, Karel Pacak

College of Health and Life Sciences

Aix-Marseille University
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland.
UT MD Anderson Cancer Center
University Hospital
Memorial Sloan Kettering Cancer Center, New York
University of Oxford
University of Sydney
Icahn School of Medicine at Mount Sinai
Sorbonne Paris Cité, Université Paris Diderot
Dankook University
University of Cambridge
Uppsala University
University of Montreal
National Cancer Institute
Department of Surgery, University of Otago, Christchurch, New Zealand
University Hospital Carl Gustav Carus at the TU Dresden
Bernard and Shirlee Brown Glaucoma Research Laboratory, Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY 10032, USA.
University of Florida
St Vincent's Hospital Medical School
IdEx University of Strasbourg
National Institutes of Health
University of Groningen, University Medical Center Groningen
University Medical Center Utrecht
Centre de recherche du Centre hospitalier de l'Université de Montréal
University of Toronto
Division of Biomedical Sciences, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK.; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK.
Spanish National Cancer Research Center (CNIO)
Seth GS Medical College and KEM Hospital
National Center for Global Health and Medicine
Division of Endocrine Surgery
Radboud University Medical Center
From the George Institute for Global Health, University of New South Wales Sydney (V.P., M.J.J., B.N., S. Bompoint), the Royal North Shore Hospital (V.P.), Concord Repatriation General Hospital (M.J.J.), and the Charles Perkins Centre, University of Sydney (B.N.), Sydney, and the Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW (C.P.) - all in Australia; Imperial College London (B.N.) and the Department of Renal Medicine, UCL M
Division of Endocrinology
Stanford University School of Medicine

Research output: Contribution to journal › Review article › peer-review

104 Citations (SciVal)

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.

Original language	English
Pages (from-to)	168-184
Number of pages	17
Journal	Nature Reviews Endocrinology
Volume	20
Issue number	3
Early online date	14 Dec 2023
DOIs	https://doi.org/10.1038/s41574-023-00926-0
Publication status	Published - Mar 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41574-023-00926-0

Cite this

Taïeb, D., Nölting, S., Perrier, N. D., Fassnacht, M., Carrasquillo, J. A., Grossman, A. B., Clifton-Bligh, R., Wanna, G. B., Schwam, Z. G., Amar, L., Bourdeau, I., Casey, R. T., Crona, J., Deal, C. L., Del Rivero, J., Duh, Q.-Y., Eisenhofer, G., Fojo, T., Ghayee, H. K., ... Pacak, K. (2024). Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. Nature Reviews Endocrinology, 20(3), 168-184. https://doi.org/10.1038/s41574-023-00926-0

@article{aa5a59896e9048b1bc27499d3bd28695,

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

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.",

author = "David Ta{\"i}eb and Svenja N{\"o}lting and Perrier, \{Nancy D\} and Martin Fassnacht and Carrasquillo, \{Jorge A\} and Grossman, \{Ashley B\} and Roderick Clifton-Bligh and Wanna, \{George B\} and Schwam, \{Zachary G\} and Laurence Amar and Isabelle Bourdeau and Casey, \{Ruth T\} and Joakim Crona and Deal, \{Cheri L\} and \{Del Rivero\}, Jaydira and Quan-Yang Duh and Graeme Eisenhofer and Tito Fojo and Ghayee, \{Hans K\} and Anne-Paule Gimenez-Roqueplo and Gill, \{Antony J\} and Rodney Hicks and Alessio Imperiale and Abhishek Jha and Kerstens, \{Michiel N\} and \{de Krijger\}, \{Ronald R\} and Andr{\'e} Lacroix and Ivica Lazurova and Lin, \{Frank I\} and Charlotte Lussey-Lepoutre and Maher, \{Eamonn R\} and Ozgur Mete and Mitsuhide Naruse and Naris Nilubol and Mercedes Robledo and Fr{\'e}d{\'e}ric Sebag and Shah, \{Nalini S\} and Akiyo Tanabe and Thompson, \{Geoffrey B\} and Timmers, \{Henri J L M\} and Jiri Widimsky and Young, \{William J\} and Leah Meuter and Lenders, \{Jacques W M\} and Karel Pacak",

year = "2024",

month = mar,

doi = "10.1038/s41574-023-00926-0",

language = "English",

volume = "20",

pages = "168--184",

journal = "Nature Reviews Endocrinology",

issn = "1759-5029",

publisher = "Nature Publishing Group",

number = "3",

}

Taïeb, D, Nölting, S, Perrier, ND, Fassnacht, M, Carrasquillo, JA, Grossman, AB, Clifton-Bligh, R, Wanna, GB, Schwam, ZG, Amar, L, Bourdeau, I, Casey, RT, Crona, J, Deal, CL, Del Rivero, J, Duh, Q-Y, Eisenhofer, G, Fojo, T, Ghayee, HK, Gimenez-Roqueplo, A-P, Gill, AJ, Hicks, R, Imperiale, A, Jha, A, Kerstens, MN, de Krijger, RR, Lacroix, A, Lazurova, I, Lin, FI, Lussey-Lepoutre, C, Maher, ER, Mete, O, Naruse, M, Nilubol, N, Robledo, M, Sebag, F, Shah, NS, Tanabe, A, Thompson, GB, Timmers, HJLM, Widimsky, J, Young, WJ, Meuter, L, Lenders, JWM & Pacak, K 2024, 'Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement', Nature Reviews Endocrinology, vol. 20, no. 3, pp. 168-184. https://doi.org/10.1038/s41574-023-00926-0

TY - JOUR

T1 - Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants

T2 - an international expert Consensus statement

AU - Taïeb, David

AU - Nölting, Svenja

AU - Perrier, Nancy D

AU - Fassnacht, Martin

AU - Carrasquillo, Jorge A

AU - Grossman, Ashley B

AU - Clifton-Bligh, Roderick

AU - Wanna, George B

AU - Schwam, Zachary G

AU - Amar, Laurence

AU - Bourdeau, Isabelle

AU - Casey, Ruth T

AU - Crona, Joakim

AU - Deal, Cheri L

AU - Del Rivero, Jaydira

AU - Duh, Quan-Yang

AU - Eisenhofer, Graeme

AU - Fojo, Tito

AU - Ghayee, Hans K

AU - Gimenez-Roqueplo, Anne-Paule

AU - Gill, Antony J

AU - Hicks, Rodney

AU - Imperiale, Alessio

AU - Jha, Abhishek

AU - Kerstens, Michiel N

AU - de Krijger, Ronald R

AU - Lacroix, André

AU - Lazurova, Ivica

AU - Lin, Frank I

AU - Lussey-Lepoutre, Charlotte

AU - Maher, Eamonn R

AU - Mete, Ozgur

AU - Naruse, Mitsuhide

AU - Nilubol, Naris

AU - Robledo, Mercedes

AU - Sebag, Frédéric

AU - Shah, Nalini S

AU - Tanabe, Akiyo

AU - Thompson, Geoffrey B

AU - Timmers, Henri J L M

AU - Widimsky, Jiri

AU - Young, William J

AU - Meuter, Leah

AU - Lenders, Jacques W M

AU - Pacak, Karel

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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.

UR - https://www.nature.com/articles/s41574-023-00926-0

UR - https://www.scopus.com/pages/publications/85180214116

U2 - 10.1038/s41574-023-00926-0

DO - 10.1038/s41574-023-00926-0

M3 - Review article

C2 - 38097671

SN - 1759-5029

VL - 20

SP - 168

EP - 184

JO - Nature Reviews Endocrinology

JF - Nature Reviews Endocrinology

IS - 3

ER -

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

Abstract

UN SDGs

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