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- Svenja Nölting
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland
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- Nicole Bechmann
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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- David Taieb
- Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, 13273 Marseille, France
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- Felix Beuschlein
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland
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- Martin Fassnacht
- Department of Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Würzburg, Germany
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- Matthias Kroiss
- Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany
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- Graeme Eisenhofer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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- Ashley Grossman
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX2 6HG, UK
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- Karel Pacak
- Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD 20847, USA
説明
<jats:title>Abstract</jats:title><jats:p>Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters based on underlying genetic alterations. With around 30% to 35% of Caucasian patients (a lower percentage in the Chinese population) showing germline mutations in susceptibility genes, pheochromocytomas/paragangliomas have the highest rate of heritability among all tumors. A further 35% to 40% of Caucasian patients (a higher percentage in the Chinese population) are affected by somatic driver mutations. Thus, around 70% of all patients with pheochromocytoma/paraganglioma can be assigned to 1 of 3 main molecular clusters with different phenotypes and clinical behavior. Krebs cycle/VHL/EPAS1-related cluster 1 tumors tend to a noradrenergic biochemical phenotype and require very close follow-up due to the risk of metastasis and recurrence. In contrast, kinase signaling–related cluster 2 tumors are characterized by an adrenergic phenotype and episodic symptoms, with generally a less aggressive course. The clinical correlates of patients with Wnt signaling–related cluster 3 tumors are currently poorly described, but aggressive behavior seems likely. In this review, we explore and explain why cluster-specific (personalized) management of pheochromocytoma/paraganglioma is essential to ascertain clinical behavior and prognosis, guide individual diagnostic procedures (biochemical interpretation, choice of the most sensitive imaging modalities), and provide personalized management and follow-up. Although cluster-specific therapy of inoperable/metastatic disease has not yet entered routine clinical practice, we suggest that informed personalized genetic-driven treatment should be implemented as a logical next step. This review amalgamates published guidelines and expert views within each cluster for a coherent individualized patient management plan.</jats:p>
収録刊行物
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- Endocrine Reviews
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Endocrine Reviews 43 (2), 199-239, 2021-06-19
The Endocrine Society