SAT-073 - Refractory Hypoglycemia Due to Functional Transformation of A Nonfunctioning Pancreatic Neuroendocrine Tumor Treated with the Investigational Insulin Receptor Antibody Ersodetug

Background:
Malignant insulinomas are rare neuroendocrine tumors that cause severe endogenous hyperinsulinemic hypoglycemia and are often metastatic. Rarely, previously nonfunctioning pancreatic neuroendocrine tumors (PanNETs) can acquire insulin secretion, resulting in difficult-to-control hypoglycemia. Management becomes particularly challenging when hypoglycemia is refractory to standard medical, interventional, and oncologic therapies.Ersodetug (RZ358) is an investigational allosteric monoclonal antibody that is a non-competitive antagonist of the insulin receptor thereby reducing insulin signaling and represents a novel therapeutic approach to insulin induced hypoglycemia.


Case Presentation:
A 58-year-old woman with metastatic nonfunctioning PanNET involving the liver, bone, and breast, status post distal pancreatectomy, splenectomy, and liver debulking, presented with one year of worsening symptomatic hypoglycemia. Episodes persisted despite discontinuation of all diabetes medications and dietary modification. Continuous glucose monitoring showed frequent glucose values in the 30–50 mg/dL range. During hypoglycemia, plasma glucose was 11 mg/dL with markedly elevated insulin (82.36 μIU/mL) and C-peptide (5.76 ng/mL), consistent with endogenous hyperinsulinemic hypoglycemia and concerning for malignant insulinoma due to functional tumor transformation.
Interventions and

Results:
Despite aggressive treatment with high-dose diazoxide (up to 10 mg/kg/day), corticosteroids, continuous intravenous dextrose (D10–D25), octreotide, hepatic bland embolization, and everolimus, the patient remained profoundly hypoglycemic and required MICU admission for hourly glucose monitoring. FDA emergency authorization was obtained for use of ersodetug. Following initiation, glycemic control improved, allowing discontinuation of diazoxide and complete weaning off intravenous dextrose. Hypoglycemia resolved, enabling transfer out of the MICU and subsequent hospital discharge. Euglycemia has been maintained for several months on continued ersodetug therapy despite ongoing metastatic disease.

Conclusion:
This case illustrates rare functional transformation of a nonfunctioning PanNET into a malignant insulinoma and demonstrates the effectiveness of insulin receptor antagonism with ersodetug in treating life-threatening, refractory hypoglycemia. Ersodetug may be a valuable therapeutic option for tumor-associated hyperinsulinemic hypoglycemia when conventional treatments fail.

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