Endocrine Abstracts

Germline mutations in the succinate-dehydrogenase subunits A, B, C, and D (SDHA/B/C/D) predispose to development of the phaeochromocytoma-paraganglioma (FPGL) syndromes. SDHC and SDHD are anchoring proteins located in the inner mitochondrial membrane. The SDH complex has two major roles in energy production it is part of the tricarboxic acid cycle catalysing the oxidative dehydrogenation of succinate coupled to the reduction of ubiquinone. It is also the complex II component of the electron transport system. Mutations in SDHC are present in ~4% of Head-Neck paraganglioma (HNPGL) patients. In a paraganglioma cohort more than 80% of patients with SDHC mutations had HNPGL and two had a thoracic FPGL. We now report a 64 years old woman with a cerebral paraganglioma with metastases to the neck. Thirty years ago, the patient was diagnosed with a glomus tumor in the middle ear and received radiotherapy. In 2009, a MR scan revealed a large tumor in the posterior fossa. Histological examination showed an atypical neuroendocrine carcinoma, positive for chromogranin A and synaptophysin. The Ki67 index was 30%. Urine catecholamines, plasma metanephrines and plasma chromogranin A were 5 to 7 times upper normal limits. The patient was treated with neurosurgery and chemotherapy. Due to neck lymph node metastasis, radionuclide therapy is currently under consideration. Analysis of the SDHC gene revealed a 17 basepair germline deletion (c.191_207del17) in exon 4. The deletion causes a frameshift and has not been described before. The patient’s son and two brothers were not interested in genetic testing.

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.