Metastatic proinsulin-secreting tumor: a rare cause of persistent hypoglycemia

Proinsulin-secreting neuroendocrine tumors (NETs) are a rare cause of severe hypoglycemia, characterized by normal or low insulin levels and disproportionate elevations of proinsulin. Clinical features and optimal management of unresectable cases remain poorly defined, in part due to such few cases described in the literature. We describe a 47-year-old female with metastatic large-cell neuroendocrine carcinoma who presented with obstructive jaundice and was incidentally found to have profound, asymptomatic fasting hypoglycemia. Initial insulin and C-peptide levels were within reference ranges, but proinsulin concentrations were markedly elevated. The patient developed recurrent, refractory hypoglycemia requiring high-dose corticosteroids, glucagon, diazoxide, octreotide, and ultimately central-line infusion of 70% concentrated dextrose via total parenteral nutrition. Glycemic control could not be achieved despite maximal medical therapy, and the patient experienced rapid clinical deterioration leading to comfort-focused hospice management. This case highlights the diagnostic challenges of proinsulin-driven hypoglycemia and underscores the need for earlier recognition and improved treatment pathways for patients with proinsulin-secreting NETs.