Successful treatment with sirolimus in patients with congenital hyperinsulinism: A case series

Congenital hyperinsulinism (CHI) is the most frequent cause of persistent hypoglycemia in the neonatal period. Management of unresponsive forms of CHI to conventional treatment represents a medical challenge. We report a case series of two infants with CHI refractory to therapy with diazoxide and octreotide, who were treated with sirolimus, a mammalian target of rapamycin inhibitor. The first infant was preterm with hypoglycemia with hyperinsulinism, detected immediately after birth, started on diazoxide at 72 hours of age with no response, and subsequently put on increasing doses of octreotide and sent home after 2 weeks with normoglycemia. Positron emission tomography with CT (PET-CT) showed diffuse pancreatic involvement and genetic studies confirmed a mutation involving the KCNJ11 gene. She redeveloped hypoglycemic seizures at 3 months of age and was started on sirolimus therapy with monitoring of blood sirolimus levels, which was withdrawn at 3 years of age and she continues to be normoglycemic at 7 years of age. The second infant, a male term baby developed CHI at birth, and did not respond to diazoxide or octreotide. He had a diffuse disease on PET-CT with a mutation in the ABCC8 gene. He was put on sirolimus therapy with mild hypoglycemic episodes in first year and was asymptomatic at the end of 2 years. Our cases demonstrated an effective response to sirolimus with no major adverse effects seen during follow-up. We recommend that a trial with sirolimus should be performed before pancreatectomy, in infants with diffuse CHI unresponsive to diazoxide and octreotide due to ABCC8 and KCNJ11 mutations.