Endocrine Abstracts

Section 1: Case history: 75 year old female diagnosed with Grade 1 pNET (Ki-67 index 70%) in 2018. Treated with subtotal pancreatectomy but 8 months post-surgery a follow up scan showed new liver metastases, at which point she was commenced on lanreotide. 3 months later she presented with an 8 week history of episodic weakness, sweating and confusion consistent with hypoglycaemia. These episodes initially improved with eating but had become more severe and unresponsive to carbohydrates prior to admission.

Section 2: Investigations: Capillary glucose was undetectable in the Emergency Department. She was admitted for further investigations and underwent a supervised fast with plasma insulin, glucose and C-peptide measurements.

Section 3: Results and treatment: 24 h fast confirmed hypoglycaemia with glucose 2.2 mmol/l, C-peptide 1117 pmol/l, total insulin 26.6 mU/l, consistent with endogenous insulin secretion. Urinary sulphonylurea screens were negative. She was given dietary advice and oral prednisolone was commenced with some improvement in symptoms, but early morning hypoglycaemia persisted. CT showed progression of liver metastases, but no other sites of disease. She therefore underwent re-biopsy of a liver lesion at the same time as hepatic arterial embolization. Biopsy confirmed high grade transformation to grade 3 pNET/carcinoma, with mitotic index >90%, positive CD56, chromogranin and synaptophysin and negative stain for insulin. This resulted in resolution of hypoglycaemia and she has now commenced chemotherapy with Carboplatin and Etoposide.

Section 4: Conclusions and points for discussion: Non-functioning pancreatic NETs rarely acquire hormone secretion. In this case there was evidence of endogenous insulin secretion only several months after liver metastases developed, in the context of high grade transformation. Notably there were no symptoms suggestive of hypoglycaemia at the time of the original presentation with a pancreatic primary NET. We hypothesise that the transformation to a high grade neuroendocrine tumour was associated with dysregulated hormone secretion. Although the liver biopsy did not stain for insulin the brisk improvement in hypoglycaemia following hepatic artery embolization suggests the liver metastases were the source of the hyperinsulinaemia.