SAT-551 Endogenous Hyperinsulinemic Hypoglycemia and Methadone: A Rare Case of Endocrine Dysfunction in a Complex Patient

Abstract Disclosure: A. Balkan: None. S. Mon: None. M. Masood: None. Background: Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare condition characterized by excessive endogenous insulin production leading to recurrent hypoglycemia. Common causes include insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome, insulin autoimmune syndrome, and post-bariatric surgery hypoglycemia. Methadone, a synthetic μ-opioid receptor agonist used for opioid addiction treatment and pain management, has been rarely implicated in hypoglycemia, potentially due to insulin secretion stimulation. Flory et al. observed a dose-dependent association between methadone and hypoglycemia, particularly at doses exceeding 40 mg/day. Case Description: A 60-year-old female with a history of prediabetes, end-stage renal disease (ESRD) on hemodialysis, and heroin use disorder maintained on methadone therapy (105 mg/day) presented with chest pain. During her hospitalization, she experienced recurrent severe hypoglycemia despite adequate oral intake. Workup revealed endogenous hyperinsulinemic hypoglycemia with insulin level >3, C-peptide level >0.2, and a negative sulfonylurea/meglitinide screen in a fasting state. Insulin autoantibody, Beta-hydroxybutyrate level and TSH levels were within normal limits. Imaging studies revealed no definite abnormalities in the pancreas, pituitary and adrenal glands. Given her high dose methadone therapy and absence of other clear causes, the methadone dose was tapered, leading to stabilization of her glucose levels. Steroid replacement therapy was initiated for suspected adrenal insufficiency after recurrent episodes of hypotension which led to the stabilization of her blood pressure; however, cortisol levels and ACTH stimulation testing were not performed prior to starting treatment, leaving adrenal insufficiency (AI) unconfirmed. Learning Points: •Methadone, though rarely, can precipitate EHH and should be considered in the differential diagnosis of hypoglycemia in patients on high-dose opioid therapy.•Chronic opioid therapy, particularly at high doses, necessitates monitoring for endocrine dysfunctions, including adrenal insufficiency.•Timely identification and management of EHH in patients with coexisting conditions, such as ESRD and long-term opioid therapy, are critical to avoid severe complications. Conclusion: This case highlights the rare but clinically significant endocrine effects of methadone, including its potential to induce EHH. Awareness and vigilance in managing such cases are essential, especially in complex patients with multiple comorbidities. Proactive monitoring and tailored interventions can improve outcomes and prevent life-threatening complications. Presentation: Saturday, July 12, 2025