Endocrine Abstracts

Seventeen years ago, germline mutations in the SDHD gene were reported to be associated with familial head and neck paraganglioma (HNPGL) and, subsequently, sporadic and familial phaeochromocytoma and paraganglipoma (PPGL). Thereafter germline mutations in other succinate dehydrogenase subunit genes (SDHB, SDHC, SDHA) were also found to predispose to HNPGL and PPGL. Succinate dehydrogenase has critical roles in the Krebs cycle and respiratory chain electron-t...

Seventeen years ago, germline mutations in the SDHD gene were reported to be associated with familial head and neck paraganglioma (HNPGL) and, subsequently, sporadic and familial phaeochromocytoma and paraganglipoma (PPGL). Thereafter germline mutations in other succinate dehydrogenase subunit genes (SDHB, SDHC, SDHA) were also found to predispose to HNPGL and PPGL. Succinate dehydrogenase has critical roles in the Krebs cycle and respiratory chain electron-t...

Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by endocrinologists. Over the last decade, major advances have been made in understanding the molecular genetic basis of adrenal and extra-adrenal phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra-adrenal functional paraganglioma (eFPGL)). In contrast to the previously held belief that only 10% of cases had a genetic component, currently about one third of all aPCA/eFPGL c...

Predisposition to phaeochromocytoma is a feature of germline succinate dehydrogenase subunit mutations (SDHB, SDHC and SDHD), von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia (MEN) types 2A and 2B and neurofibromatosis type 1. However, although each of these disorders is associated with phaeochromocytoma they differ with respect to susceptibility to other associated tumours, However despite this clinical heterogeneity, there is evidence for sh...

Recent advances in determining the molecular basis for phaeochromocytoma susceptibility have suggested a much larger inherited contribution to the pathogenesisof phaeochromocytoma than had been generally recognized. The identification of individuals with phaeochromocytoma susceptibility disorders (e.g. von Hippel-Lindau disease, succinate dehydrogenase subunit mutations, multiple endocrine neoplasia type 2 and neurofibromatosis type 1) is important because of the opportunity t...

Background: The enzyme succinate dehydrogenase (SDH) functions in the citric acid cycle and loss of function of this enzyme can lead to the development of phaeochromocytoma/paraganglioma (PPGL), gastrointestinal stromal tumour (GIST) and renal cell carcinoma. A germline mutation in one of the four genes (SDH-A/B/C/D) encoding the SDH complex is the most common mechanism of SDH inactivation causing SDH deficiency and is routinely screened for...

Mutations affecting the mitochondrial enzyme succinate dehydrogenase (SDH) are associated with a wide spectrum of tumours. SDH deficient tumours have a unique tumour metabolome due to the interruption of the citric acid cycle and accumulation of the ‘oncometabolite’ succinate, which drives tumourigenesis. Investigating the tumour metabolome of SDH deficient tumours has potential translational application. MRI spectroscopy (1H-MRS) was used for in vivo<...

Background: Up to a third of subjects who develop a phaeochromocytoma or a paraganglioma will do so as the result of mutations in one of several familial genes. Identifying a causative mutation may have significant implications for family screening and future disease surveillance.Objective: To review the frequency and type of genetic testing undertaken in subjects presenting to our unit over a 20-year period who have developed a phaeochromocytoma and/or ...

Approximately 40% of phaeochromocytomas and paragangliomas (PPGL) are associated with a germline mutation. These individuals have a lifetime tumour risk and in the case of SDHx germline mutations, there is a risk of multiple tumours and malignancy. We sought to discover plasma metabolites associated with succinate dehydrogenase (SDH) deficiency and tumorigenesis for potential use as predictive and/or prognostic biomarkers. Plasma samples were collected prospectively from a cli...

Background: International consensus supports interval biochemical and imaging surveillance for all asymptomatic carriers of succinate dehydrogenase (SDHx) gene mutations and patients with a history of SDH deficient tumours. There is growing awareness that the life time penetrance of the SDHx genes is much lower than that originally estimated and that long term radiological surveillance carries a significant risk including ionizing radiation exposure and incidental findings. Th...