Case Report: Pasireotide treatment in neonatal congenital hyperinsulinism due to a homozygous ABCC8 mutation

Vollständiger Abstract

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Mutations in ABCC8 and KCNJ11 are associated with the most severe and diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are commonly used off-label as second-line treatment. While octreotide and lanreotide are the most established options, pasireotide—a second-generation somatostatin analogue with higher affinity for somatostatin receptor subtype 5—has been hypothesized to offer improved suppression of insulin secretion. We report the off-label use of subcutaneous pasireotide in an infant with severe CHI due to a homozygous ABCC8 mutation. The patient presented with severe persistent hypoglycemia despite high-dose octreotide, continuous glucagon infusion, and high carbohydrate requirement. The established next step would have been a subtotal pancreatectomy. Following detailed counseling, the parents expressed a strong preference to defer surgical intervention and to pursue further medical options. Thus, an individualized therapeutic trial with subcutaneous pasireotide was initiated at approximately 8 weeks of age as an attempt to avoid surgery. However, pasireotide at doses of up to 0.11 mg/kg/day administered every 4 h did not lead to substantial clinical improvement. Instead, treatment was associated with increased glycemic variability, as reflected by more frequent episodes of hypo- and hyperglycemia, ultimately requiring reintroduction of glucagon as rescue therapy. No adverse effects were observed. Due to the lack of therapeutic response, pasireotide was discontinued after 8 days and the patient underwent near-total pancreatectomy. In conclusion, intermittent pasireotide injections were not associated with clinical improvement in this infant with medically refractory CHI, and its use potentially contributed to increased glycemic variability and instability. Further studies are needed to evaluate the safety and efficacy of pasireotide in this vulnerable patient population.