ESPE Abstracts

Background: Lanreotide, a prolonged-release somatostatin analogue, has been utilized off-label for nearly a decade to treat cases of congenital hyperinsulinism (CHI) that do not respond to diazoxide. Acute side-effects of Lanreotide include diarrhoea and topical allergic reactions. Long-term effects include hepatitis, gallstones, growth suppression, hypothyroidism and gastrointestinal dysmotility. However, limited number of case series have documented the long-term side-effects of Lanreotide in children with CHI.

Objective: To assess safety of Lanreotide in a large cohort of children with CHI.

Methods: Longitudinal observational study was conducted at our Highly Specialized CHI centre, documenting the side-effects experienced by individuals with CHI who underwent Lanreotide treatment from 2013 to 2023. A side-effect was defined as any anomaly identified in liver function tests LFT, abdominal ultrasound, growth indicators, thyroid function tests or allergic reactions arising after Lanreotide administration.

Results: 64 CHI patients received Lanreotide treatment. KATP channelopathy emerged as the predominant genetic form of CHI and majority had diffuse disease confirmed in 31/37 via an 18F DOPA PET/CT scan or suspected based on their genotype. Only a few (3) had focal CHI as per scan report or histopathology report, while 2 had atypical disease on the scan. The median age of Lanreotide initiation was 30.5 months (3-201 months), with a median follow-up age of 114 months (11-6168 months). Acute side-effects, were observed in 30% (19/64), predominantly presenting as abdominal symptoms (pain, diarrhoea) with only 9% (5/64) experiencing topical allergic reactions at the site of Lanreotide injection. Data on long-term side-effects of Lanreotide were collected from 57 patients, with 3 individuals discontinued Lanreotide treatment due to the acute side-effects, 2 stopped within 6 months due to unresponsiveness, 2 lost to follow-up. None of our patients developed NEC, despite Lanreotide administration starting at 3 months of age. The primary side-effect observed was elevated liver enzymes (15 AST, 13 GGT, 5 ALT) and coagulation abnormalities in 7 patients. Additionally, 8 patients developed gall stones. Remarkably, growth was unaffected, as evidenced by the median height SDS improving from -0.18 before Lanreotide treatment to 0.26 post Lanreotide administration, while suppressed IGF1 was noted in two patients. Finally, one patient developed central hypothyroidism.

Conclusion: Long-term use of Lanreotide for managing CHI led to abnormalities in LFT and increased the risk of gallstones. However, discontinuing Lanreotide was not necessary. It is crucial to monitor LFT in all patients receiving Lanreotide.