Pheochromocytoma: implications in tumorigenesis and the actual management.
Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
U
U
Shah
A
A
Giubellino
K
K
Pacak
D019797:3-Iodobenzylguanidine / Q000627:therapeutic use; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000315:Adrenalectomy / Q000379:methods; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002395:Catecholamines / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D019468:Disease Management; D004621:Embolization, Therapeutic; D016514:Genes, Neurofibromatosis 1; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D010673:Pheochromocytoma / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
D000970:Antineoplastic Agents; D002395:Catecholamines; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D019797:3-Iodobenzylguanidine; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human