Lanreotide Is a Safe and Effective Treatment for Congenital Hyperinsulinism

Abstract

Background: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia and is associated with high risk of neurodevelopmental delays if not effectively treated. For children who are unresponsive to diazoxide (the only FDA-approved treatment for HI), treatment options are limited. The second line therapy is somatostatin analogues (including short-acting octreotide and long-acting lanreotide), but their effectiveness may be limited by tachyphylaxis and side effects. Aims: We describe a single center’s experience with the use of lanreotide to treat congenital HI. Methods: Retrospective chart review of patients with HI treated with lanreotide. Results: Fifty patients with HI initiated therapy with lanreotide. Associated diagnoses included Beckwith-Wiedemann syndrome (n=2), MEN-1 (n=2), Turner syndrome (n=1), Kabuki syndrome (n=1) and Usher syndrome (n=1). Genetic screening identified 32 mutations (KATP channel: n=28, glucokinase: n=4). No mutation was identified in 11 patients. In total, 16 (32%) patients had a near-total pancreatectomy and six (12%) had a partial pancreatectomy (n=6). The median age at initiation of lanreotide was 1.6 yrs (range: 9 mos-18.1 yrs). At initiation of lanreotide, medical therapy included (single or combo): octreotide, enteral dextrose and diazoxide. Twenty-three patients were able to discontinue octreotide and 16 were able to discontinue enteral dextrose. Children received lanreotide alone (n=13), lanreotide/enteral dextrose (n=15) and lanreotide/diazoxide (n=8). Seven subjects were not responsive to lanreotide and discontinued treatment. Two patients discontinued treatment due to side effects, one for developing diabetes post-pancreatectomy, and another for HI resolution. Side effects included nodules at the injection site (n=10), gallstones (n=2), GI upset (n=2), pancreatic insufficiency (n=1), and headaches (n=1). Conclusions: Overall, Lanreotide treatment was effective for children with HI. Side effects were rare, but a longer duration of treatment is necessary to fully determine their frequency. The majority of children were able to transition from multiple daily octreotide injections to monthly lanreotide. Future studies are needed to identify risk factors for lanreotide failure. Clinical implications: Lanreotide appears to be an effective treatment option for many children with congenital HI that are unresponsive to diazoxide. The monthly interval dosing may be preferred compared to multiple daily octreotide injections.