Sirolimus Therapy and Follow-up in a Patient with Severe Congenital Hyperinsulinism Following Subtotal Pancreatectomy

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of severe, persistent hypoglycemia in neonates and infants. If the patient does not respond to medical treatment the currently available treatment is subtotal pancreatectomy, but some patients still experience severe hypoglycemia after surgery. Sirolimus, a mammalian target of rapamycin inhibitor has recently been reported to be effective in the treatment of insulinoma and CHI patients. Here we report a patient with CHI who had prolonged hypoglycemia after subtotal pancreatectomy. The patient had a heterozygous mutation in ABCC8 but was unresponsive to an optimal dose of diazoxide (15 mg/ kg/day) and octreotide (30 μg/kg/day). The patient subsequently had subtotal pancreatectomy but severe and persistent hypoglycemia continued post-operatively. Sirolimus was commenced. There was a remarkable improvement in glycemic control without major adverse events, although he required a small dose of octreotide to maintain euglycemia. Sirolimus therapy was discontinued when the patient was 15 months old. At the time of this report, at an age of three years and eight months, the patient continues to maintain good glycemic control. This report suggests that sirolimus may be an effective treatment option in patients with CHI resistant to established medical therapy or failure of ubtotal pancreatectomy. However, the long-term safety requires study in larger groups of very young patients.

Keywords: ABCC8; hypoglycemia; mTOR; sirolimus; Congenital hyperinsulinism.

Figure 1

Sanger sequencing of ABCC8 gene in the proband and his parents: the arrows showed the mutation site of the ABCC8 gene

Figure 2

Histopathological result confirmed diffuse hyperplasia of the islet cells. The arrows showed hypersecretion of islet cells in islets