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.
- MeSH
- dítě MeSH
- dospělí MeSH
- feochromocytom * genetika terapie diagnóza MeSH
- lidé MeSH
- nádory nadledvin * genetika terapie diagnóza MeSH
- paragangliom * genetika terapie MeSH
- sukcinátdehydrogenasa genetika MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.
- MeSH
- feochromocytom * diagnóza genetika terapie MeSH
- lidé MeSH
- nádory nadledvin * diagnóza genetika terapie MeSH
- paragangliom * diagnóza genetika terapie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- sukcinátdehydrogenasa genetika MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
: 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.
- MeSH
- biomedicínský výzkum MeSH
- feochromocytom * diagnóza genetika terapie MeSH
- hypertenze * MeSH
- konsensus MeSH
- lidé MeSH
- nádory nadledvin * diagnóza genetika terapie MeSH
- paragangliom * diagnóza genetika terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
- Geografické názvy
- Evropa MeSH
Pheochromocytomas and paragangliomas are chromaffin cell tumors that produce, store (e.g. in vesicles), metabolize (e.g. to yield metabolites such as normetanephrine or metanephrine), and secrete (release) catecholamines (e.g. norepinephrine and epinephrine, or dopamine). The metabolism of catecholamines is a more consistent process than that of catecholamine secretion. Pheochromocytomas are found in the adrenal gland; closely related tumors of extra-adrenal location are classified as paragangliomas. Most pheochromocytoma and paraganglioma tumors (PTTs) represent sporadic tumors but about 20-30% of these tumors are familial. Mutations in six genes to date have been identified to be responsible for familial PTTs: 1. the von Hippel-Lindau (VHL) gene leading to VHL syndrome; 2. the RET gene leading to multiple endocrine neoplasia type 2; 3. the neurofibromatosis type 1 (NF-1) gene associated with von Recklinghausens disease; and 4 and 5. mutations of genes encoding the B, C, and D subunits of mitochondrial succinate-dehydrogenase (SDHB, SDHC, and SDHD) associated with familial PTTs. The presence of catecholamine excess reflects various clinical signs and symptoms associated with PTTs. Hypertension is the most common sign and may be sustained or paroxysmal. Numerous independent studies have now confirmed that measurements of fractionated metanephrines (i.e. normetanephrine and metanephrine measured separately) in urine or plasma provide superior diagnostic sensitivity over measurement of the parent catecholamines. Current localization of PTTs should be based on the use of anatomical as well as specific functional imaging studies to proof that a tumor is indeed pheochromocytoma or paraganglioma. Laparoscopic surgery is now the technique of first choice for resection adrenal and extra-adrenal PTTs. All patients with PTTs should receive appropriate preoperative medical management to block the effects of released catecholamines (blocking the synthesis and the action of catecholamines). Currently, there is no curative treatment for malignant PTTs.
- MeSH
- alfa blokátory terapeutické užití MeSH
- alfa-methyltyrosin terapeutické užití MeSH
- diferenciální diagnóza MeSH
- fenoxybenzamin terapeutické užití MeSH
- feochromocytom diagnóza genetika chirurgie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- metastázy nádorů terapie MeSH
- paragangliom diagnóza genetika chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- dítě MeSH
- dospělí MeSH
- falešně negativní reakce MeSH
- falešně pozitivní reakce statistika a číselné údaje MeSH
- feochromocytom diagnóza sekrece MeSH
- klinické chemické testy metody normy statistika a číselné údaje MeSH
- lidé středního věku MeSH
- lidé MeSH
- metanefrin krev moč MeSH
- mladiství MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
