Endocrine Abstracts

Phaeochromocytomas are catecholamine-secreting tumors that usually arise from the adrenal medulla. Catecholamine-secreting tumors may also develop in retroperitoneal, pelvic or thoracic paraganglia. Here, we use the term phaeochromocytoma for catecholamine-secreting adrenal or extra-adrenal tumors. Before 2000, 10 to 15% of the patients with phaeochromocytoma were reported to have family or phenotypic evidence of a hereditary disease: multiple endocrine neoplasia type 2 (MEN2; in about 7% of cases), von Hippel-Lindau disease (VHL; 3%) and neurofibromatosis type 1 (NF1; 1%). In 2% of cases a family history of phaeochromocytoma was found, but with no evidence of these syndromes. There were also reports of phaeochromocytomas in hereditary paraganglioma (HPGL) families, who usually develop non-functional head and neck tumors associated with the parasympathetic nervous system. In 2000–2001, mutations in SDHB, SDHC and SDHD genes, that encode the B, C and D subunits of mitochondrial succinate dehydrogenase, were identified in most HPLG families. In 2002, Neumann reported that 66 of 271 patients (24%) with an apparently sporadic phaeochromocytoma had unexpected germline mutations in the RET, VHL or SDH genes. In 2005, our group diagnosed hereditary phaeochromocytoma (VHL, MEN2, NF1, HPGL) in 86 of 314 patients (27%) with phaeochromocytoma and identified an unexpected germline mutation in 30 of the 258 patients (12%) with no evidence of a syndromic or familial disease. These findings suggested that about one phaeochromocytoma carrier in three, including 10 to 15% of the patients with an apparently sporadic presentation, had hereditary disease. Most mutations detected in apparently sporadic cases affected the SDHB gene. SDHB mutation carriers had larger tumors and a more frequent metastatic evolution than those without. These new findings have important consequences for the management of patients with phaeochromocytoma and their families.