OC49 - Phenotypic transformation of a non-functioning pancreatic neuroendocrine tumour to a hormonally active insulinoma

Introduction Pancreatic neuroendocrine tumours (PNETs) are typically classified as functioning (35%) or non-functioning (65%) based on hormonal activity. While transformation from non-functioning to functioning PNET is rare, such phenotypic plasticity presents diagnostic and therapeutic challenges. This case describes a young woman with a well-differentiated, metastatic non-functioning PNET which, nearly six years after diagnosis, transformed into a hormonally active insulinoma. Case A 27 year old Caucasian female presented with abdominal pain and jaundice and was diagnosed with a grade 2 non-functioning PNET with bilobar liver metastases. She underwent multimodal treatment over the next 5 years, including somatostatin analogues, neoadjuvant chemotherapy (FCiST, CAPTEM), Whipple’s procedure, and peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. 5 years and 9 months following initial diagnosis, the patient developed sudden onset, severe spontaneous hypoglycaemia. This was investigated with a supervised fast, which confirmed hyperinsulinaemic hypoglycaemia due to endogenous insulin excess (glucose 1.6 mmol/L, c-peptide 5.8 ng/ml, insulin 24.1 µIU/mL). This was attributed to a metachronous conversion of a non-functioning PNET to a functioning PNET – an insulinoma. Additional PRRT cycles with capecitabine were administered with disease response, including stabilisation of glucose levels, regression of hypoglycaemia and radiological improvement. A total of six PRRT treatment sessions were delivered. However, after time, progression recurred, and the patient was considered a candidate for further 177Lu-PRRT with CAPTEM, or alpha-PRRT. Discussion This case illustrates a rare phenotypic transformation of PNET to insulinoma, a process potentially influenced by liver metastases and tumour microenvironment. Such functional conversions may present late and subtly, increasing the risk of more severe consequences including hypoglycaemia, highlighting the importance of vigilance for such symptoms even years after initial diagnosis. PRRT remains a valuable treatment in both functional and non-functional PNETs, as demonstrated by the initial response in this patient, though responses may diminish over time. Alpha- PRRT, with its higher linear energy transfer and shorter tissue penetration, offers promise in refractory cases. Further data is needed to guide treatment for functionally transformed PNETs. This case highlights the need for dynamic monitoring and evolving therapeutic strategies in the long-term care of PNET patients.