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The citric acid cycle, also known as the Krebs cycle, plays an integral role in cellular metabolism and aerobic respiration. Mutations in genes encoding the citric acid cycle enzymes succinate dehydrogenase, fumarate hydratase and malate dehydrogenase all predispose to hereditary tumour syndromes. The succinate dehydrogenase enzyme complex (SDH) couples the oxidation of succinate to fumarate in the citric acid cycle and the reduction of ubiquinone to ubiquinol in the electron transport chain. A loss of function in the succinate dehydrogenase (SDH) enzyme complex is most commonly caused by an inherited mutation in one of the four SDHx genes (SDHA, SDHB, SDHC and SDHD). This mechanism was first implicated in familial phaeochromocytoma and paraganglioma. However, over the past two decades the spectrum of tumours associated with SDH deficiency has been extended to include gastrointestinal stromal tumours (GIST), renal cell carcinoma (RCC) and pituitary adenomas. The aim of this review is to describe the extended tumour spectrum associated with SDHx gene mutations and to consider how functional tests may help to establish the role of SDHx mutations in new or unexpected tumour phenotypes.

Summary A 40-year-old Caucasian female presented with hyperglycaemia, polyuria, polydipsia and weight loss of 6 kg over a 1-month period. There was no personal or family history of malignancy or diabetes mellitus. On examination, she was jaundiced with pale mucous membranes and capillary glucose was 23.1 mmol/L. Initial investigations showed iron deficiency anaemia and obstructive pattern of liver function tests. HbA1c was diagnostic of diabetes mellitus at 79 mmol/mol. Malignancy was suspected and CT chest, abdomen and pelvis showed significant dilatation of intra- and extra-hepatic biliary tree including pancreatic duct, with periampullary 30 mm mass lesion projecting into lumen of duodenum. Enlarged nodes were seen around the superior mesenteric artery. This was confirmed on MRI liver. Fasting gut hormones were normal except for a mildly elevated somatostatin level. Chromogranin A was elevated at 78 pmol/L with normal chromogranin B. Duodenoscopy and biopsy showed possible tubovillous adenoma with low-grade dysplasia, but subsequent endoscopic ultrasound and biopsy revealed a grade 1, well differentiated neuroendocrine tumour. The patient was started on insulin, transfused to Hb >8 g/dL and Whipple’s pancreatico-duodenectomy was undertaken. This showed a well-differentiated neuroendocrine carcinoma arising in duodenum (Grade G1 with Ki67: 0.5%), with areas of chronic pancreatitis and preservation of pancreatic islet cells. There was complete resolution of diabetes post Whipple’s procedure and patient was able to come of insulin treatment. Her last HBA1C was 31 mmol/mol, 4 months post tumour resection. Learning points: Diabetes mellitus and malignancy can be related. A high index of suspicion is needed when diabetes mellitus presents atypically. Non-functional neuroendocrine tumours can present with diabetes mellitus.

Aims: To determine the cause of death of people with type 2 diabetes in Ayrshire and Arran between 2009 and 2014 compared to the national mortality rate. Methods: The primary cause of death (as noted on the death certificates) of 2116 patients with type 2 diabetes between the years 2009 and 2014 were collated. The causes of death were clustered into nine categories- heart disease, stroke, infection, renal failure, respiratory disorders, cancer, mental health, decompensated diabetes and other. The total rates were then compared to national rates using Standardised Mortality Ratio (SMR) and then individually due to heart disease, cerebrovascular disease and cancer. Results: The most common cause of death in the cohort was cancer (27.8%) followed by heart disease (24.1%). SMR for type 2 diabetes was 145 (95% CI 139,152; p15 years). SMR for strokes was elevated in the 55-74 age range with no significant gender difference. Cancer deaths in males was not significantly elevated (SMR 109) but it was elevated in females (120, 95% CI 104,137) (p Conclusions: The all-cause mortality for patients with type 2 diabetes was consistently higher across all age brackets. The greatest differences were noted in females with heart disease aged less than 65. Disclosure C. Meney: None. A. Collier: None. M.D. Hair: None. L. Cameron: None. C. Bisambar: None. J. Ilyas: None.