Background: Persistent hyperinsulinaemic hypoglycaemia (HH) of infancy (PHHI) is a rare condition which presents with severe hypoglycaemia during the neonatal period. For medically unresponsive forms of diffuse HH, subtotal pancreatectomy was previously the only treatment option, with the potential consequences of recurrence of hyperinsulinism, diabetes mellitus and exocrine pancreatic insufficiency. The novel use of sirolimus treatment was recently reported in four infants who achieved good glycaemic control. We report our experience with Sirolimus in an infant with PHHI.
Case presentation: A neonate was diagnosed with PHHI when she presented with severe refractory hypoglycemia at birth. She was initially treated with diazoxide at 20 mg/kg per day and a carbohydrate-rich diet. She responded well with minimal hypoglycaemia until 7 months of age when she started having episodes of recurrent hypoglycaemia. The side effects of diazoxide she experienced were hypertrichosis and decreased appetite. Mutational analysis demonstrated that she was heterozygous for a novel missense mutation on the ABCC8 gene. An 18-F DOPA PET scan showed that she had diffuse disease. At 18 months, she was commenced on sirolimus at an initial dose of 0.5 mg/m2 per day, gradually increasing weekly until the dose was 4.8 mg/m2 per day, with a therapeutic trough between 2030 ng/ml. Diazoxide was eventually discontinued 2 months after sirolimus was started. She has continued on sirolimus for the past 8 months. She only experienced one episode of severe hypoglycemia contributed by viral gastroenteritis, during which the sirolimus trough was suboptimal at 13 ng/ml. Side effects included mild elevation of transaminases and asymptomatic elevation of creatine kinase level.
Conclusion: Sirolimus therapy is an alternative to subtotal pancreatectomy in severe diffuse PHHI, avoiding the side effects of hypertrichosis and fluid retention associated with diazoxide therapy. However, the duration of therapy in PHHI and the long term side effects have yet to be established.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology