GLP-1 Receptor Agonist Associated Unmasking of Insulinoma

Insulinoma is a rare functional pancreatic neuroendocrine tumour and the most common cause of endogenous hyperinsulinaemic hypoglycaemia in adults. Diagnosis is frequently delayed due to non-specific and intermittent symptoms, and a high index of suspicion is needed.

We report the case of a 40-year-old non-diabetic woman who presented with recurrent episodes of weakness shortly after initiation of a glucagon-like peptide-1 receptor agonist (GLP-1RA). Laboratory evaluation demonstrated inappropriately elevated insulin and C-peptide levels during documented hypoglycaemic events, consistent with endogenous hyperinsulinaemia. Autoimmune and exogenous causes were excluded. Imaging studies identified a 2 cm hypervascular pancreatic lesion, with functional imaging confirming somatostatin receptor avidity consistent with an insulin-secreting tumour. The patient was initially treated with diazoxide as a bridge to definitive management. She subsequently underwent laparoscopic distal pancreatectomy, with histopathology confirming a well-differentiated pancreatic neuroendocrine tumour (WHO Grade 1). Following surgery, hypoglycaemia resolved completely.

This case highlights the potential of GLP-1 receptor agonist therapy to unmask an insulinoma. Many benign insulinomas exhibit abundant expression of GLP-1 receptors. While a high index of suspicion remains essential, awareness of the emerging association between the incretin-based therapies and unexplained hypoglycaemia may facilitate earlier diagnosis.

Hypoglycaemia is a rare but significant clinical event, and thorough evaluation is mandatory.Widely used GLP-1RA medications are glucose-dependent and therefore rarely cause hypoglycaemia; occurrence should prompt clinical suspicion for an underlying cause.Benign insulinomas express high levels of GLP-1 receptors; consequently, GLP-1 RAs may induce otherwise unexplained hypoglycaemia and can be used as tracers to localise difficult to detect tumours.