8798 How Low Can You Go: Suspected Methadone-Induced Hyperinsulinemia

Abstract Disclosure: L. Ravindra: None. M.G. Fernandez: None. V. Cheng: None. Background: Studies have shown that methadone use can result in severe hypoglycemia. This is thought to be related to methadone having antagonistic activity at NMDA receptors, resulting in increased pancreatic insulin release, suppressed glucagon and epinephrine, and inhibition of hepatic glycogenolysis. These mechanisms affect the normal physiologic response to hypoglycemia and can result in hyperinsulinemic-induced hypoglycemia. Clinical case: We present a case of a 56-year-old male with complex regional pain syndrome managed with a high daily dose of methadone (345 mg) who presented to the hospital for evaluation of failure to thrive and hypoglycemia. During the hospital admission, evaluation of hypoglycemia included a serum blood glucose level of 41 mg/dL (normal >60 mg/dL), with an inappropriately normal level of insulin 10 (Reference Range (RR) 3-25 mU/L), C-peptide 2.9 (RR 0.5-3.3 ng/ml), Pro-insulin 2.9 (RR 3-20 pmol/L), an undetectable level of Beta-hydroxybutyrate <0.10 (RR 0.02-0.27 mMol/L) negative insulin antibodies <0.4 (RR 0.0 - 0.4 U/mL), and negative sulfonylurea screen. Additional labs included a normal TSH of 2.8 (RR 0.3-5.5 mIU/ml) and appropriate morning cortisol of 23 (RR >14-15 μg/dL). The abdominal CT and follow-up MRI did not reveal any definite abnormalities in the pancreas. Given persistent evidence of hyperinsulinemic-induced hypoglycemia, a PET Dotatate scan was performed, confirming the absence of a neuroendocrine tumor. While admitted, management included nutritional optimization, close glucose monitoring, and an intravenous dextrose infusion. Diazoxide was also initiated and gradually increased to 150 mg three times a day. Addiction Medicine assisted in tapering down the methadone dose from 115 mg to 105 mg three times a day. With these interventions, the patient had no further episodes of hypoglycemia. On discharge, the patient was provided with a continuous glucose monitor. On follow-up, the patient has continued to show improvement and the diazoxide dose has been decreased without recurrent hypoglycemia. Given this, a selective arterial calcium stimulation test was not pursued. Conclusion: Methadone is an uncommon cause of hyperinsulinemic-induced hypoglycemia. Suspicion should arise, particularly in patients on high doses. Current evidence suggests tapering methadone dosage as the primary intervention, as insulin levels can decrease drastically and improve hypoglycemia. This therapeutic approach should be considered before pursuing invasive and costly diagnostic testing. Presentation: 6/3/2024