Effective and safe use of sirolimus in hyperinsulinemic hypoglycaemia refractory to medical and surgical therapy: a case series and review of literature

Abstract

Abstract Objectives Hyperinsulinemic hypoglycaemia (HH) presents significant management challenges, especially in cases refractory to standard therapies. This case series aims to report the efficacy and safety of sirolimus, an mTOR inhibitor, as an adjunctive therapy in persistent HH, noting that current clinical guidelines caution its use outside of research. Case presentation We report a case series from two paediatric endocrinology centres across Australia, describing use of sirolimus in four infants with persistent HH refractory to conventional treatments or post near-total pancreatectomy. Retrospective chart reviews provided clinical and biochemical data, documenting each patient’s sirolimus dosing, treatment responses, and adverse events. Conclusions Sirolimus emerged as a useful and safe adjunct, enabling hospital discharge, and demonstrating efficacy even at lower serum trough levels. Despite safety concerns, including recurrent viral infections in one patient, sirolimus was generally well-tolerated. We advocate for implementing risk mitigation strategies, including a multidisciplinary approach, and maintaining lower sirolimus trough levels than previously recommended. Careful consideration of sirolimus is warranted in select cases of severe diffuse HH, emphasising ongoing monitoring for adverse effects and further research to refine treatment guidelines.