Management of Hereditary Pheochromocytoma
Roderick John Clifton-Bligh, MBBS,PhD,FRACP
Royal North Shore Hospital
Management of hereditary pheochromocytoma/paraganglioma (PPGL) syndromes requires expert multidisciplinary care. Since 30-40% of PPGL cases will be associated with a germline pathogenic variant, arguably all PPGL cases should have comprehensive genetic testing for germline predisposition variants in at least RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, TMEM127 and MAX; NF1 is usually diagnosed on clinical grounds. Risk of hereditary predisposition increases with younger age, extra-adrenal tumor location, syndromic features and positive family history. Syndromic but non-hereditary forms of PPGL should also be considered including the Pacak-Zhuang syndrome (mosaic EPAS1 mutations) and Carney Triad (SDHC promoter methylation). Conversely, finding somatic pathogenic variants in HRAS or FGFR1 is near-definitive evidence of sporadic PPGL. Penetrance and clinical behavior of PC/PGL varies specifically between each of these genes. Genetic testing of families requires expert counseling. Lifelong screening for tumor development is recommended for even asymptomatic patients with a positive genetic test result.