Case history: 22 year old female presented with left sided hemiparesis following a generalised seizure; the blood glucose was 1.2 mmol/l. Corrective treatment restored cerebral function. In the preceding 6 months, she had symptoms of drowsiness on waking which corrected with sugary drinks and described tiredness with lethargy. There had been no reported change in appetite or bowel habits however, there had been a degree of weight loss during this period. During hospital admission, 20% dextrose infusion was required to maintain euglycaemia.
Investigations: Blood samples during a spontaneous hypoglycaemic episode (1.5 mmol/l) demonstrated elevated insulin level 392 pmol/l (18173 pmol/l) and C-peptide 3913 pmol/l (3701470 pmol/l) with a negative sulphonylurea screen. CT scan revealed 3 indeterminate bilobar hepatic lesions which were further characterised as metastatic disease on MRI with an exophytic lesion identified in the pancreatic body. Gallium DOTATATE demonstrated avidity of pancreatic and hepatic lesions in keeping with a pNET (Insulinoma) in the body/tail and 4 DOTATATE-avid hepatic metastases. EUS was not tolerated and liver biopsy was performed.
Results and treatment: Histology from the liver biopsy showed a metastatic well-differentiated neuroendocrine tumour with a Ki-67 proliferation index 1% (G1). Genetic testing was negative for mutations in MEN1, AIP and CDKN1B. Diazoxide (up to 400 mg/day) was commenced without any benefit and hypoglycaemia remained refractory despite increased doses of Octreotide (200 mcg TDS) and depot Lanreotide (120 mg) injections. She required continuous 20% Dextrose infusion throughout this prolonged admission (10 weeks). Everolimus was commenced with addition of oral Dexamethasone for appetite stimulation which rapidly restored euglycaemia. Following a distal pancreatectomy, partial splenectomy and two segment liver resections she has remained normoglycaemic whilst withdrawing medications.
Conclusion: This case highlights the challenge of managing refractory hypoglycaemia in an unusually young presentation of metastatic insulinoma. There were large volume metastases and marked hyperinsulinaemia. Everolimus is a protein kinase inhibitor (mTOR) used in several cancers including pNETs. Through inhibition of the PI3K/AKT/MTOR pathways everolimus can normalise blood glucose levels by inhibition of gluconeogenesis and reduction of insulin secretion. Our patient remained dextrose dependent, despite SSA, prednisolone and diazoxide, until the introduction of everolimus which had rapid and sustained effects in achieving glucose control. Other treatments considered included pasireotide, PRRT, Chemo/Radio Embolisation and cytotoxic chemotherapy but the response to everolimus allowed safe discharge until surgical resection of disease was undertaken.
08 - 10 Apr 2019
Society for Endocrinology