Endocrine Abstracts

Introduction: In most patients with familial history of pheochromocytoma/paraganglioma, leads in the majorty of cases to a postive genetic testing for mutations, and what’s more in those patients with no familial antecedents, about 10–25% carry a mutation in one related gene. In these cases other aspects like, bilaterality, multiplicity or location must be taken into account.

Objective: The objective of the study was to discuss the importance of genetic testing in apparently sporadic cases.

Design: Nine probands, with no familial or personal antecedents of pheochromocytoma or paraganglioma, were analyzed for the major genes: VHL, RET, SDHB, SDHC and SDHD.

Results: Nine probands (six men and three women) with an average of 55.8±10.3 years old were analyzed, 8 cases (88.8%) of pheochromocytoma and only one proband with non-fuctioning paragangliomas (mediastinal paraganglioma and glomus jugulare tumor). Genetic analysis was performed using a multi-gene panel testing for the major genes, for analyzing patients’ blood and tumor samples. A rate of 33.3% for genetic mutations was found: RET (C634S) (1 of 9) and SDHD (c.242C>T (p.Pro81Leu)) (1 of 9), VHL (pVal84/Met) (1 of 9), in this last case no mutations were found on blood sample but the mutation for VHL was found in paraffin embedded sample. In our serie, genetic testing was performed on first grade relatives of patients affected, being diagnosed two first grade relatives of mutations during the study: one for VHL mutation and one for RET mutation, in this last case, with initial diagnosis of medullary thyroid cancer and development of pheochromocytoma in a five year follow-up interval.

Conclusions: We recommend genetic testing in all patients, not only in those with familial antecedents but also in sporadic tumors, regardless of age or location (In our serie 80% were unilateral adrenal masses, 10% bilateral masses and 10% extraadrenal location). We emphasise the importance of genetic testing in first grade relatives, as in our serie, in 22% of probands affected of pheochromocytoma/ paraganglioma, at least one first grade relative was carrier of the mutation.

References: 1. Cascón A, Montero-Conde C, Ruiz-Llorente S, Mercadillo F, Leton R, Rodrıguez-Antona C, Martınez-Delgado B, Delgado M, Dıez A et al. Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot Genes, Chromosomes & Cancer. 2006;45:213–219.

2. Koch CA, Vortmeyer AO, Huang SC, Alesci S, Zhuang Z, Pacak K 2001 Genetic aspects of pheochromocytoma. Endocr Regul 35:43–52.