Endocrine Abstracts

A 65 years old male chef presented with a history of weight loss of 15kg over a 12-month period associated with lethargy, constipation and abdominal pain. His past medical history included epilepsy, hypertension and gastric reflux. He reported no family history of endocrinopathies.At presentation his performance status was 0 and was found to have hepatomegaly. In view of rapid weight loss and hepatomegaly he had a CT scan of the abdomen and pelvis, which showed multiple hypervascular liver metastases, bony metastases, and a heterogeneous enhancing distal pancreas tumour with tiny fleck of calcification over the pancreas body/tail. He underwent a liver biopsy, which was consistent with grade 3 neuroendocrine tumour (strong staining with synaptophysin,chromogranin A and CD56, patchy staining with AE 1/3, p63 and TTF1) with a Ki67 index of 33% with no expression of both insulin and glucagon on immunohistochemistry.A Tc-99m-tektrotyd scintigraphy revealed extensive avidity in liver lesions, retroperitoneal mesenteric nodes and bony lesions. His urine 5- HIAA was normal at 18unol (5–35), HbA1c 31 mmol/mol, PTH 1.7 pmol/l (1.8–6.8), calcium 2.39 mmol/l (2.20–2.60). He was given FCIST chemotherapy [5-fluorouracil, cisplatin and streptozocin] which has minimal impact in tumour progression. After NET MDT discussion, he underwent 3 cycles of Peptide Receptor Radionuclide Therapy (PRRT) with post therapy images demonstrating good tumour targeting. Subsequently, he developed hypoglycaemia during chemotherapy. After a brief fast, his glucose dropped to 1.5 mmol/l, he had raised C-peptide of 1797 pmol/l (<300), insulin 26 mu/l (<3) in keeping with an insulinoma. After his third fraction of PRRT he presented with an erythematous erosive rash with associated desquamation and some annular components affecting the trunk and limbs. He was noted to have glossitis. The clinical features were in keeping with a glucagonoma-related necrolytic migratory erythema and were supported by skin histology. His glucagon was significantly raised at 1465 pmol/l (0–50). The original liver biopsy at diagnosis was reviewed and it was negative for insulin and glucagon staining. Despite the introduction of Diazoxide, octreotide and dexamethasone, he had persistent hypoglycaemia and was admitted for intravenous dextrose infusion. He developed pancytopenia, deteriorated rapidly and sadly passed away 12 months after his initial presentation.

Conclusion

Pancreatic neuroendocrine tumours have varied presentations. Metachronous functional as well as histological heterogeneity have been reported. This case is unique with co-existent glucagon and insulin hypersecretion.We hypothesize this was the result of different metastatic lesions expressing varied differentiation and secretory capacity, adding to the challenges of managing these tumours.