Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma

Buffet, Alexandre; Aim, Laurène Ben; Leboulleux, Sophie; Drui, Delphine; Vezzosi, Delphine; Libé, Rossella; Ajzenberg, C.; Bernardeschi, Danièle; Cariou, Bertrand; Chabolle, F.; Chabre, Olivier; Darrouzet, V.; Delemer, Brigitte; Desailloud, Rachel; Goichot, B.; Esvant, A.; Offredo, Lucile; Herman, Philippe; Laboureau, S.; Lefebvre, Herve; Raingeard, I.; Reznik, Yves; Sadoul, Jean‐Louis; Hadoux, Julien; Tabarin, Antoine; Tauveron, Igor; Zénaty, Delphine; Favier, Judith; Bertherat, Jérôme; Baudin, Éric; Amar, Laurence; Gimenez‐Roqueplo, Anne‐Paule

doi:10.1530/endoabs.63.oc5.1

Cited by 7 publications

(11 citation statements)

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“…Second, about 40% or more of patients with SDHB mutation have metastatic phenotype as the principal predictor of malignancy in PPGL patients [57,93,94]. Third, patients with genetic or syndromic PPGL have higher risks in development for PPGL complications compared to those with apparently sporadic disease [94,96]. Fourth, about 11% to 13% of patients with apparently sporadic PPGLs such as single benign PPGL without a family history have a mutation in susceptibility genes according to a meta-analysis [97].…”

Section: Genetic Testing For Pheochromocytoma/paraganglioma 51 Genetic Testing Is Recommended In All Patientsmentioning

confidence: 99%

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Kim

et al. 2021

Endocrinol Metab

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Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

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Section: Genetic Testing For Pheochromocytoma/paraganglioma 51 Genetic Testing Is Recommended In All Patientsmentioning

confidence: 99%

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Kim

et al. 2021

Endocrinol Metab

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“…Screenings advices do not only differ between the different mutations, but also over time, because studies on penetrance differ over time regarding the population studied (index included or not), the imaging methods used and the duration of follow‐up. Adherence to screening, leads to the detection of smaller PCC/PGL and might even lead to an improved survival for patients who develop metastases, although this is based on only few patients …”

Section: Phenotype Of Sdhx Mutation Carriersmentioning

confidence: 99%

“…Adherence to screening, leads to the detection of smaller PCC/PGL and might even lead to an improved survival for patients who develop metastases, although this is based on only few patients. 16 Until now, a clear explanation for the difference of the clinical picture between different SDHx mutations is lacking, except for the hypothesis that the extent of SDH deficiency or loss depends on the subunit. Apart from the differences, all SDHx mutations are characterized by the (potential) presence of PGL/PCC.…”

Section: Phenotype Of Sdhx Mutation Carriersmentioning

confidence: 99%

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

et al. 2019

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Succinate dehydrogenase (SDH) mutations lead to the accumulation of succinate, which acts as an oncometabolite. Germline SDHx mutations predispose to paraganglioma (PGL) and pheochromocytoma (PCC), as well as to renal cell carcinoma and gastro-intestinal stromal tumors. The SDHx genes were the first tumor suppressor genes discovered which encode for a mitochondrial enzyme, thereby supporting Otto Warburg's hypothesis in 1926 that a direct link existed between mitochondrial dysfunction and cancer. Accumulation of succinate is the hallmark of tumorigenesis in PGL and PCC. Succinate accumulation inhibits several α-ketoglutarate dioxygenases, thereby inducing the pseudohypoxia pathway and causing epigenetic changes. Moreover, SDH loss as a consequence of SDHx mutations can lead to reprogramming of cell metabolism. Metabolomics can be used as a diagnostic tool, as succinate and other metabolites can be measured in tumor tissue, plasma and urine with different techniques. Furthermore, these pathophysiological characteristics provide insight into therapeutic targets for metastatic disease. This review provides an overview of the pathophysiology and clinical implications of oncometabolite succinate in SDHx mutations. K E Y W O R D S oncometabolites, paraganglioma, pheochromocytoma, SDH mutation, succinate 1 | INTRODUCTION Mutations of genes encoding for the succinate dehydrogenase (SDH) complex, associated with familial paraganglioma (PGL) and pheochromocytoma (PCC), lead to accumulation of succinate, which disturbs the metabolic regulation of the cell. Nowadays metabolic dysregulation is recognized as one of the eight hallmarks of cancer. 1 Although germline mutations in SDHx genes are predominantly linked to PGL and PCC, these mutations also predispose to renal cell carcinoma (RCC), gastrointestinal stromal tumors (GISTs) and, possibly, pituitary adenomas. PCC, PGL and head and neck PGL (HNPGL) are rare neuroendocrine tumors arising from chromaffin cells that can synthesize and release catecholamines. Sympathetic PGLs are derived from sympathetic paraganglia in the chest, abdomen or pelvis. PCC are PGLs located in the adrenal medulla. 2 HNPGLs are derived from parasympathetic paraganglia. Common locations for HNPGLs include the carotid body and the middle ear, as well as the vagus nerve and internal jugular vein. While parasympathetic PGLs are most often non-functional tumors, PCC and sympathetic PGL release catecholamines into the circulation and can

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“…Regarding the peculiar autosomal dominant inheritance pattern of SDHD-related PGL, which is associated with a maternal genomic imprinting, a presymptomatic genetic testing of the offspring is recommended for those who are at risk of receiving the SDHD mutation from his father. Actually, it has been recently proved that an early determination of the genetic status has a positive impact on the management and clinical outcome of SDHx mutations carriers (29).…”

Section: Discussionmentioning

confidence: 99%

“…Pheochromocytoma is one of the tumors with very strong genotype-phenotype correlations. Extensive genetic research over the past decade revealed new pheochromocytoma susceptibility genes, so at present familial forms are estimated to be almost 40% (29). Uncommon clinical presentation or biochemical profile as well as unusual comorbidities in patients with PPGL may open a window to new discoveries in the field of genetics of this rare tumor (29,34,41).…”

Section: Discussionmentioning

confidence: 99%

40-Year Follow-Up of a Patient with Multiple Paragangliomas and a SDHD Mutation

et al. 2019

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Context. Germline mutations in Succinate Dehydrogenase Complex Subunit D gene (SDHD) predispose to predominantly benign head and neck and/or thoracic-abdominal pelvic paragangliomas (PGLs). Objective. We present the case of a patient carrying a germline SDHD mutation responsible for multiple PGLs, who was followed for 40 years. He was initially diagnosed with a left cervical PGL at the age of 23 years, treated by surgery. Then, he recurred and developed a multifocal disease. The second-line therapeutic option was a threedimensional conformal radiotherapy performed in 2008. In 2013 the patient had clinical, hormonal, PET-and SPECT-CT data revealing a disease progression. The treatment with the long-acting somatostatin analogue Octreotide Lar was carried out till the patient's death caused by pulmonary embolism in December 2014. Results. Complex treatment led to a long clinical and biochemical remission and control of tumor growth. Conclusions. Despite their usually benign behavior, multicentric SDHD-related PGLs can require a multimodal approach involving surgery, radiotherapy and medical treatment for providing a long-term control of the disease and maintaining a good quality of life.

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Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma

Cited by 7 publications

References 0 publications

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

40-Year Follow-Up of a Patient with Multiple Paragangliomas and a SDHD Mutation

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