Endocrine Abstracts

Hereditary pheochromocytoma/paraganglioma (PHEO/PGL) syndrome is a rare disease. It has been demonstrated that about 25% of the apparently sporadic PHEO/PGL are due to a germ line mutation in one of the susceptibility genes, such as, VHL, RET, NF1, TMEM127, MAX and the genes encoding the four subunits of the mitochondrial enzyme succinate dehydrogenase (SDH) as well as the gene encoding one SDH assembly factor, SDHAF2. SDH is located in the inner mitochondrial membrane and is formed by four subunits: SDHA–B–C–D. It is an enzyme involved in the tricarboxylic acid cycle and in the mitochondrial electron transport chain.

Beside the pivotal role played by mitochondria in modulating programmed cell death and other fundamental processes within cells, the first incontestable examples of causality between mitochondrial dysfunction and tumorigenesis were only discovered when mutations in SDH were found to be the initiating events of familial PHEO/PGL.

Germ line mutations in SDHD, SDHAF2, SDHC and SDHB genes are responsible for the occurrence of different syndromes named PGL1, PGL2, PGL3 and PGL4 respectively. Also mutations of SDHA can predispose to functioning PHEO/PGL (PGL5 ?). PGL1 presents benign, non-secreting, multiple head and neck PGLs (HN-PGL) not frequently associated with PHEOs and/or abdominal secreting PGLs. PGL2 presents only HN-PGLs. PGL3 is mainly characterized by single HN-PGL but recently abdominal secreting PGL has also been reported. PGL4 presents PHEO or abdominal/thoracic PGL, which, at variance with tumors developed in PGL1 and PGL3, are malignant in up to 30% of cases, leading to metastatic disease. PGL1 and PGL2 are parent of origin diseases and only carriers of the mutation in the paternal allele can develop tumors of the paraganglia. Overall, SDH mutations accounts for 3–5% of PHEO/PGL presenting as apparently sporadic.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.