SAT-224 Clinical Outcomes of Chlorothiazide Monotherapy in Select Neonates with Hyperinsulinemic Hypoglycemia

Abstract Disclosure: X. Xu: None. R.S. Aguirre: None. Y. Lin: None. Objective: To evaluate the clinical outcomes of chlorothiazide monotherapy for select neonates with hyperinsulinemic hypoglycemia (HH) in the Neonatal Intensive Care Unit (NICU) at our institution. Methods: Retrospective chart review. Background: The combination of diazoxide and chlorothiazide is a common pharmacological treatment for infants with HH. However, concerns about pulmonary hypertension associated with diazoxide have made some neonatologists cautious about its use, particularly in premature infants. In our NICU, chlorothiazide monotherapy has been considered as an alternative initial treatment for HH, especially in preterm neonates who often exhibit transient hyperinsulinism that resolves over time. To date, no studies have reported on the use of chlorothiazide as a standalone therapy for HH in infants. In adults, thiazide diuretics have been shown to marginally increase fasting glucose (3.6-4.9 mg/dL) and decrease insulin sensitivity. Animal studies suggest these effects may result from direct inhibition of insulin release, impaired glucose uptake in peripheral tissues, cyclic AMP-mediated stimulation of glycogenolysis, and inhibition of glycogenesis. Results: Between July 2023 and July 2024, fourteen neonates with HH were treated with chlorothiazide monotherapy in our NICU. Of these, three infants required the addition of diazoxide, and one resumed total parenteral nutrition (TPN). Two infants discontinued chlorothiazide due to hyponatremia. Prior to discharge, eight infants successfully passed safety fasting tests, either while continuing chlorothiazide or after weaning off chlorothiazide. Notably, five of these eight infants underwent feeding optimization during treatment, which may have contributed to their improvement. Conclusions: Chlorothiazide monotherapy may provide partial benefit for some infants with HH, although confounding factors, such as feeding optimization, must be considered. The potential neurodevelopmental consequences of delaying standard therapies warrant careful evaluation. Larger studies are needed to assess the efficacy and safety of chlorothiazide monotherapy as an alternative treatment for select neonates with HH. Presentation: Saturday, July 12, 2025