Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: An international expert Consensus statement Review
| Authors: | 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.; Gimenez-Roqueplo, A. P.; Gill, A. J.; Hicks, R.; Imperiale, A.; Jha, A.; Kerstens, M. N.; de Krijger, R. R.; Lacroix, A.; Lazurova, I.; Lin, F. I.; Lussey-Lepoutre, C.; Maher, E. R.; Mete, O.; Naruse, M.; Nilubol, N.; Robledo, M.; Sebag, F.; Shah, N. S.; Tanabe, A.; Thompson, G. B.; Timmers, H. J. L. M.; Widimsky, J.; Young, W. J.; Meuter, L.; Lenders, J. W. M.; Pacak, K. |
| Review 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. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023. |
| Keywords: | adult; cancer chemotherapy; child; genetics; sunitinib; systemic therapy; cancer adjuvant therapy; cancer radiotherapy; neoadjuvant therapy; temozolomide; nuclear magnetic resonance imaging; lymph node dissection; cytoreductive surgery; gene; paraganglioma; dacarbazine; metastasis; quality of life; computer assisted tomography; cell growth; clinical assessment; genetic variability; cyclophosphamide; vincristine; surgical approach; hypoxia; tumor burden; active surveillance; cell migration; consultation; upregulation; (3 iodobenzyl)guanidine i 131; pheochromocytoma; biochemistry; cell invasion; germ-line mutation; angiography; adrenal tumor; adrenal gland neoplasms; catecholamine urine level; genetic counseling; metadrenalin; catecholamine blood level; personalized medicine; alpha adrenergic receptor blocking agent; succinate dehydrogenase; adrenalectomy; germline mutation; first-line treatment; laparoscopic adrenalectomy; radionuclide therapy; open surgery; sdhb gene; whole body mri; bilateral adrenalectomy; first-degree relative; humans; human; article; positron emission tomography-computed tomography; artificial embolization; microwave thermotherapy; oxodotreotide lutetium lu 177; 3 o methyldopamine; sdhb protein, human; minimally invasive adrenalectomy; partial adrenalectomy; pseudohypoxia |
| Journal Title: | Nature Reviews Endocrinology |
| Volume: | 20 |
| Issue: | 3 |
| ISSN: | 1759-5029 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-03-01 |
| Start Page: | 168 |
| End Page: | 184 |
| Language: | English |
| DOI: | 10.1038/s41574-023-00926-0 |
| PUBMED: | 38097671 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
