Endocrine Abstracts

JOINT314

Backrgound: Congenital hyperinsulinism (CHI) is a rare but severe disorder characterized by persistent hypoglycemia due to unregulated insulin secretion. Dasiglucagon, a synthetic glucagon analogue, has emerged as a promising treatment for CHI due to its stability and ease of use in continuous subcutaneous infusion. However, long-term safety data remain limited. Here, we describe a case of necrolytic migratory erythema (NME), a rare and severe dermatologic condition, associated with prolonged continuous subcutaneous dasiglucagon therapy.

Case: A male infant with CHI caused by compound-heterozygous mutations in ABCC8 was treated with continuous subcutaneous dasiglucagon after standard therapies, including intravenous glucose, diazoxide, and octreotide, failed to achieve glycemic control. Initial dasiglucagon therapy with 20–60 µg/h was effective; however, after several weeks of treatment, the patient progressively developed erythematous, scaly skin lesions. This condition was accompanied by significant malnutrition, evidenced by a consistent downward trajectory across multiple weight percentile lines in serial measurements, along with zinc deficiency and hypoaminoacidemia. Based on the patient’s history and clinical presentation, we strongly suspected necrolytic migratory erythema (NME). Given the patient’s severe skin condition a central line was chosen to ensure secure intravenous access and targeted intravenous substitution of zinc, trace elements, amino acids, and fatty acids was initiated to treat malnutrition. While we initiated further diagnostic workup for NME, the patient developed Staphylococcus aureus-associated central line sepsis. Consequently, continuous subcutaneous dasiglucagon administration was tapered and the therapy was discontinued after a total of five months. The patient underwent subtotal pancreatectomy to manage persistent hypoglycemia. Postoperatively, his condition improved significantly, with resolution of the skin lesions and normalization of nutritional parameters through targeted supplementation. As expected, diabetes mellitus developed, requiring insulin therapy.

Discussion: Dasiglucagon has shown significant promise in managing severe hypoglycemia, owing to its rapid glucose-raising effects. While short-term use has demonstrated efficacy and tolerability across various therapeutic indications, our case of prolonged continuous use in CHI, which was complicated by the development of NME, underscores the critical importance of rigorous monitoring during extended treatment. Monitoring should prioritize the early identification of potential adverse effects, including dermatological conditions, amino acid and zinc deficiencies, and alterations in weight trajectory. Although this case report does not establish a direct causal relationship between continuous dasiglucagon therapy and NME, it emphasizes the need for vigilant long-term use, multidisciplinary care, and further research to enhance the understanding of its safety profile and optimize therapeutic strategies.