Endocrine Abstracts

Case: A 69 year old man was diagnosed with poorly differentiated pancreatic adenocarcinoma with liver metastases in November 2017 and received FOLFIRINOX chemotherapy followed by Gemcitabine. This stabilised his disease and chemotherapy was stopped in March 2020. In April 2021 he presented with a 3-4 month history of tiredness; intermittent confusion, especially in the early morning; the discovery that food resolved his symptoms, albeit temporarily; and accompanying significant weight gain. A blood glucose monitor was supplied which demonstrated that his capillary blood glucose would drop as low as 1.5 mmol/l when the symptoms occurred. Biochemical assessment was consistent with insulin hypersecretion (glucose 2.0 mmol/l, insulin 109miU/l (4.4-26), C-peptide 3068 pmol/l (298-2350)). He was started on dexamethasone, diazoxide and given a Freestyle Libre 2 flash glucose monitor. Differential diagnoses included a new insulinoma in addition to his pancreatic adenocarcinoma, non-islet cell tumour hypoglycaemia or transformation of an original non-functional neuroendocrine tumour (NET) into a functional NET. Interestingly he did not have any symptoms of insulin hypersecretion at original presentation in 2017. The original histology was reviewed with immunostaining and reclassified as a WHO grade 2 NET, strongly positive for synaptophysin and CD56. Octreotide scan showed an intensely avid pancreatic lesion with extensive avid liver metastases, which were also visualised on MRI, and confirmed the diagnosis of NET. Treatment options are currently limited and will be palliative.

Discussion: It is highly unusual for NETs to transform from non-functional to functional however this transformation, especially into insulinoma, has previously been described. A possibility is that he has developed intra-tumour heterogeneity or clonal evolution as a consequence of the chemotherapy, with only some areas of tumour mass hypersecreting insulin. The flash glucose monitor has significantly improved his quality of life, allowing early detection of hypoglycaemia and prevention of hospital admission, however his general prognosis is guarded.