TO THE EDITOR: Hypoglycemia is a life-threatening complication of malignant insulinoma that can be refractory to maximal medical therapy that targets the tumor and insulin secretion and action simultaneously. We report the successful use of RZ358, a novel human anti-insulin receptor monoclonal antibody, in a patient with metastatic insulinoma in whom severe, refractory hypoglycemia developed after peptide receptor radionuclide therapy with lutetium Lu 177 dotatate. A 55-year-old man presented with a 5-month history of abdominal pain and weight loss. Imaging showed a pancreatic mass (diameter, 1.8 cm) and numerous hepatic lesions (Fig. S1A in the Supplementary Appendix, available with the full text of this letter at NEJM.org). A liver biopsy revealed a pancreatic neuroendocrine tumor (Fig. S2) with a pathogenic MEN1 mutation. Despite octreotide therapy, the abdominal pain and the tumor mass increased, thereby prompting treatment with lutetium Lu 177 dotatate. Two days after the first dose, severe hypoglycemia with neuroglycopenia (with a minimum glucose level of 20 mg per deciliter [1.1 mmol per liter]) occurred in the patient in both fasting and postprandial states. Hormonal analysis, performed when the venous glucose level was 41 mg per deciliter (2.3 mmol per liter), revealed inappropriately high levels of insulin, at 45 ;μIU per milliliter (312 pmol per liter; reference value, <19.6 μIU per milliliter [141 pmol per liter]); C-peptide, at 6.5 ng per milliliter (reference range, 0.80 to 3.85); and proinsulin, at 453 pmol per liter (reference value, <18).
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