Bethanechol-associated hyperinsulinemic hypoglycemia in a child with autonomic instability

Abstract Hyperinsulinemic hypoglycemia (HH) is a rare but potentially dangerous condition characterized by inappropriate insulin secretion. This case describes a pediatric patient with HH in the setting of autonomic instability following neurologic injury. He was started on bethanechol, a muscarinic receptor agonist, for gastric dysmotility and developed severe, persistent hypoglycemia shortly after a dose increase with laboratory findings confirming dysregulated insulin secretion. The hypoglycemia was difficult to stabilize, requiring high glucose-infusion rates. Discontinuation of bethanechol was followed by gradual resolution. This temporal association raises the possibility that cholinergic stimulation contributed to dysregulated insulin secretion in a susceptible physiologic state. Muscarinic M3 receptors on pancreatic β-cells enhance insulin secretion, although dysregulation of this pathway by M3 agonists has primarily been demonstrated in murine models and has not previously been reported in humans. This case highlights a potential link between parasympathetic signaling and insulin regulation in autonomic instability and suggests that cholinergic agents may contribute to dysregulated glucose homeostasis in susceptible patients.