SAT-449 - Recurrent Reactive Hypoglycemia in A Patient on Chronic Methadone and Long-Term Steroid Therapy Leading to Secondary Adrenal Insufficiency

Recurrent Reactive Hypoglycemia in a Patient on Chronic Methadone and Long-Term Steroid Therapy Leading to Secondary Adrenal Insufficiency

Background:
Hypoglycemia in adults not receiving insulin or insulin secretagogues is uncommon and warrants evaluation for endocrine and medication-related causes. Methadone has been increasingly associated with hypoglycemia through proposed effects on insulin secretion and impaired counter-regulatory responses. Chronic glucocorticoid exposure can result in secondary adrenal insufficiency, further disrupting glucose homeostasis. The combined contribution of these factors is rarely described.

Case Presentation:
A 71-year-old woman with type 2 diabetes mellitus (HbA1c 7.2%) presented with recurrent symptomatic hypoglycemia despite not using insulin or oral antihyperglycemic agents. Her medical history included chronic obstructive pulmonary disease treated with long-term inhaled and systemic corticosteroids and chronic pain managed with methadone 30 mg daily for approximately seven years. She reported nocturnal and post-prandial hypoglycemic symptoms, often following intake of simple sugars. Continuous glucose monitoring revealed frequent nocturnal and reactive hypoglycemic episodes, with confirmatory finger-stick glucose values in the low 50 mg/dL range. Morning laboratory evaluation showed a serum cortisol of 2.3 µg/dL with an inappropriately normal ACTH level, consistent with secondary adrenal insufficiency due to chronic glucocorticoid exposure. Other metabolic and organ function testing was unremarkable.
Physiologic hydrocortisone replacement therapy was initiated, and dietary counseling emphasized avoidance of simple sugars and consistent intake of complex carbohydrates with protein. Following treatment, hypoglycemic episodes markedly decreased, with complete resolution of nocturnal hypoglycemia and improved glycemic stability on continuous glucose monitoring. Methadone therapy was continued without dose adjustment.

Conclusion:
This case highlights a multifactorial cause of recurrent hypoglycemia involving methadone-associated metabolic effects, glucocorticoid-induced secondary adrenal insufficiency, and dietary triggers. Early recognition of adrenal insufficiency is critical in patients with unexplained hypoglycemia, particularly those on chronic opioid and steroid therapy. Correction of adrenal insufficiency and dietary modification may resolve hypoglycemia without immediate changes to methadone therapy. Continuous glucose monitoring is valuable for diagnosis and monitoring treatment response in complex hypoglycemia.

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