Insulinoma mimic: methadone-induced hypoglycaemia

Abstract

Methadone use for opioid use disorder and chronic pain has increased since the start of the century with about 4.4 million dispensed prescriptions in 2009. With increased use of methadone, there has been increasing reporting of less commonly reported side effects (ie, hypoglycaemia). Here, we describe a woman in her 70s with history of opioid use disorder on methadone, stage 4 chronic kidney disease and prior hypoglycaemic episodes who initially presented with perforated gastric ulcer requiring surgical repair. Her perioperative course was complicated by profound hyperinsulinaemic hypoglycaemia. Given concern for methadone-induced hypoglycaemia, methadone was discontinued with monitoring of subsequent blood glucose, insulin, C peptide, proinsulin, β-hydroxybutyrate and blood methadone levels. As the serum methadone levels decreased, insulin levels substantially decreased in parallel. After 21 days off methadone, dextrose infusion was discontinued with restoration of euglycaemia. In a patient with hyperinsulinaemic hypoglycaemia and methadone use, it is important to consider discontinuing methadone and re-evaluate fasting glucose levels prior to an extensive and invasive insulinoma workup.

Methadone-Induced Hypoglycemia in a Hospitalized Patient

“…Chronic methadone use is often overlooked as a possible cause of hypoglycemia despite several reports indicating the risk. [3][4][5][8][9][10] Multiple proposed mechanisms exist for how methadone may cause hypoglycemia including promotion of insulin release (ie, insulinoma mimic), impairment of gluconeogenesis, and suppression of counter-regulatory hormones (ie, glucagon). 8 Some data suggests that methadoneinduced hypoglycemia is related to adrenal insufficiency via delta or kappa receptors on the hypothalamus, leading to a decrease in adrenocorticotropic hormone (ACTH) and cortisol secretion.…”

“…[3][4][5][8][9][10] Multiple proposed mechanisms exist for how methadone may cause hypoglycemia including promotion of insulin release (ie, insulinoma mimic), impairment of gluconeogenesis, and suppression of counter-regulatory hormones (ie, glucagon). 8 Some data suggests that methadoneinduced hypoglycemia is related to adrenal insufficiency via delta or kappa receptors on the hypothalamus, leading to a decrease in adrenocorticotropic hormone (ACTH) and cortisol secretion. 4 Methadone-induced hypoglycemia also appears to be a dose-related effect, particularly at doses greater than 40 mg/ day.…”