Diazoxide-Associated Hyperglycemia: A Critical Case Precipitating Hyperosmolar Hyperglycemic State in a Child

Diazoxide is the first-line treatment for children with hyperinsulinemic hypoglycemia (HI). In these cases, diazoxide raises blood glucose levels by suppressing insulin release, preventing hypoglycemia, and potentially devastating end-organ sequelae. Hyperosmolar hyperglycemic state (HHS) is an exceedingly rare side effect of diazoxide. This complication has been described in neonates and in adults, but few children.

An 8-year-old female with genetic duplication of glucokinase, and consequent hyperinsulinemia, presented to the emergency department with evidence of hypovolemic shock secondary to severe dehydration with signs of encephalopathy. Point-of-care glucose was > 600 mg/dL. Additional labs were consistent with HHS complicated by acute kidney injury, sodium 106 mEq/L, potassium 2.5 mEq/L, chloride < 60 mEq/L, carbon dioxide 20 mEq/L, glucose 2105 mg/dL, BUN 107 mg/dL, and creatinine 3.99 mg/dL. The patient received aggressive fluid resuscitation and vasopressor support, and was admitted to the pediatric intensive care unit. A diazoxide level was obtained during admission revealing serum concentration previously shown to be associated with hyperglycemia.

We posit the patient was predisposed to hyperglycemia based on elevated diazoxide serum concentration. We hypothesize severe dehydration led to renal impairment, which decreased diazoxide clearance, causing worsening hyperglycemia and ultimately, HHS. The differential diagnosis also included diabetic ketoacidosis, surreptitious administration of diazoxide, spontaneous resolution of genetic condition, and malabsorption or excretory crisis but none of these adequately explained the patient's presentation. Regardless, this case highlights the potentially lethal complication of HHS as a side effect of diazoxide therapy.