Endocrine Abstracts

Case history: 58 year old male presented in April 2016 with haematemesis. Octreotide-avid pancreatic mass with liver metastases was identified. Liver biopsy demonstrated well differentiated Grade 2 NET (Ki-67 10–13%). He progressed on Somatostatin analogue therapy, and subsequently Sunitinib, following which he underwent four cycles of Peptide Receptor Radionuclide Therapy (PRRT) with partial response. In May 2018, there was radiological progression. He reported episodes of symptomatic hypoglycaemia, and was commenced on Everolimus. He developed recurrent hypoglycaemia despite supplemental enteral feeding.

Investigations: Fasting insulin and c-peptide levels were elevated at 239 pmol/l and 1762 pmol/l during confirmed hypoglycaemia, consistent with endogenous insulin secretion. Intra-arterial calcium-stimulated venous sampling (ASVS) demonstrated a baseline insulin level of 34.2 mU/l in the hepatic artery, peaking at 239.9 mU/l, compared to a rise from 55.3 mU/l to 102.8 mU/l in the gastroduodenal artery. This confirmed the liver metastases as the source of endogenous insulin secretion. The pancreatic gradient of less than 2 ruled out insulin secretion from the pancreatic primary, therefore excluding metastatic insulinoma.

Results and treatment: He had ongoing hypoglycaemia despite diazoxide, dexamethasone and octreotide. He proceeded to embolisation of the right liver lobe in August 2018 with resolution of hypoglycaemia. In October 2018, the hypoglycaemia recurred secondary to disease progression within the left liver lobe. His left liver lobe was successfully embolised with resolution of hypoglycaemia, which has since been sustained. He commenced further systemic therapy with Capecitabine and Temozolomide.

Conclusions and points for discussion: In summary, ectopic insulin secretion can occur in apparently non-functioning pNET, and in this case widespread metastatic disease preceded symptoms, with subsequent rapid onset of symptomatic hypoglycaemia in the absence of significant disease progression. Endogenous insulin excess was confirmed by ASVS, thus presenting an alternative mechanism of hypoglycaemia in advanced NET, distinct from the previously proposed mechanism of GLP-1/glucagon secretion¹. Localised therapy with embolisation is an effective therapy, and achieved resolution of hypoglycaemia in this case.

Reference: 1) Roberts RE et al. GLP-1 and glucagon secretion from a pancreatic neuroendocrine tumor causing diabetes and hyperinsulinemic hypoglycemia. J Clin Endocrinol Metab. 2012 Sep; 97(9):3039-45.