We present the case of a 54-year-old woman with known metastatic non-functional pancreatic NET since 2004 that developed new debilitating recurrent hypoglycemia in 2013. The patient presented in 2004 with disseminated malignancy. Radiology revealed a large pancreatic mass associated with multiple liver lesions and abdominal lymphadenopathy. Liver biopsy confirmed well differentiated NET. Initial treatment with cisplatin etoposide chemotherapy was poorly tolerated and discontinued. Subsequently interferon alpha was commenced. Tumour burden was slowly progressive, but the patient remained asymptomatic until 2013. In 2013 the patient developed recurrent hypoglycaemic episodes leading to repeated hospital admissions. This prompted repeat biopsy of a liver metastasis which demonstrated grade 1 well differentiated insulinoma. Further investigations demonstrated spontaneous hypoglycemia with a blood glucose of 1.1 mmol/l associated with inappropriately elevated C peptide and insulin. Octreotide imaging demonstrated an avid primary pancreatic lesion and multiple avid liver metastasis. The patient was commenced on somatastatin analogue therapy (SSA), but additional therapy with diazoxide and corticosteroids was required to control hypoglycaemic symptoms. Due to further disease progression the patient underwent two cycles of Yttrium-90 peptide receptor radionuclide therapy (PRRT) in 2013. PRRT led to a significant size reduction in abdominal lymphadenopathy and eliminated hypoglycaemic symptoms allowing corticosteroids and diazoxide to be discontinued. However, pancreatic and hepatic disease remained broadly stable. The patient remained asymptomatic on SSA only until 2017 when the patient developed obstructive jaundice due to disease progression and enlargement of porta-hepatic nodes. This was associated with recurrence of hypoglycaemic episodes. Bile duct stenting relieved obstructive jaundice, and the patient underwent two further cycles of PRRT, this time with leutitium-177, which again improved symptoms. Everolimus was commenced in 2018 in the context of ongoing disease progression but was poorly tolerated and subsequently stopped. Liver metastases were embolised in 2019 for symptom control. This case of transformation of non-functional pancreatic NET to functional Insulinoma demonstrates the challenge of managing a patient that experiences this extremely rare phenomenon. The symptom burden of metastatic Insulinoma is substantial and, due to the evolving course of the disease, multimodal treatment with multidisciplinary input is mandatory.
02 Dec 2019
UK and Ireland Neuroendocrine Tumour Society