Endocrine Abstracts

JOINT1819

Background: Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion, leading to severe and persistent hypoglycemia. Current medical treatment options include Diazoxide, octreotide, nifedipine, and sirolimus. However, most patients with K_ATP channel gene (ABCC8 and KCNJ11) mutations do not respond to these medications and require a near total pancreatectomy. We previously described the adjunct use of Alpelisib therapy in a three-month-old patient with CHI avoiding the need for a near total pancreatectomy (N Engl J Med. 2024;390(4):379-380).

Aims: We describe our observations in two additional patients with severe CHI treated with Alpelisib therapy, which resulted in the complete discontinuation of all existing treatments and the normalization of feeding.

Case studies: Two children (aged 3 and 4 years) with severe CHI (homozygous ABCC8 and KCNJ11 mutations) who were unresponsive to all the conventional therapies were treated with Alpelisib. The 3-year-old patient was on continuous gastrostomy feeds, received four-weekly long-acting octreotide injections, and was on diazoxide. The 4-year-old was also on continuous gastrostomy feeds overnight and 2 hourly bolus feeds during the day As well as on four-weekly long-acting octreotide. Treatment was initiated at 12. 5mg daily of Alpelisib, with gradual dose adjustments based on clinical responses. Outcome measures included blood glucose variability, frequency of hypoglycemic episodes, need for supplemental feeding, and treatment safety. In both cases, Alpelisib significantly improved glycemic control, reducing the frequency of hypoglycemic episodes. This allowed for the tapering and discontinuation of other medications (diazoxide and octreotide) and facilitated a transition to bolus gastrostomy-tube/oral feeding. No significant adverse effects were reported in either patient.

Conclusions: Alpelisib therapy shows promise as both an adjunctive and primary therapy for CHI, improving glucose control and reducing dependence on continuous feeding and other medications. Randomized controlled trials are needed to assess its long-term safety and efficacy for CHI.