Case Report: Pasireotide treatment in neonatal congenital hyperinsulinism due to a homozygous ABCC8 mutation.
Pasireotide treatment in this infant with congenital hyperinsulinism did not improve glycemic control and may have worsened glycemic variability.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This case report evaluates the use of subcutaneous pasireotide in an infant with congenital hyperinsulinism due to a homozygous ABCC8 mutation. The patient received doses up to 0.11 mg/kg/day every 4 hours for 8 days. Treatment did not lead to substantial clinical improvement and was associated with increased glycemic variability.
Abstract
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.
Background
Congenital hyperinsulinism (CHI) is often caused by mutations in genes such as ABCC8 and KCNJ11, leading to severe forms that are resistant to standard treatments like diazoxide. Somatostatin analogues, including pasireotide, are explored as second-line treatments, particularly for patients who do not respond to conventional therapies. This case report is significant as it evaluates the use of pasireotide in a neonate with a specific genetic mutation, contributing to the understanding of treatment options for this challenging condition.
Methods
This is a case report detailing the treatment of an infant with severe CHI due to a homozygous ABCC8 mutation. The patient was treated with subcutaneous pasireotide at doses of up to 0.11 mg/kg/day every 4 hours. The primary outcome was clinical improvement in glycemic control, while secondary outcomes included the frequency of hypo- and hyperglycemic episodes. The treatment duration was 8 days before discontinuation.
Results
Pasireotide treatment did not lead to substantial clinical improvement in glycemic control. Instead, it was associated with increased glycemic variability, necessitating the reintroduction of glucagon as rescue therapy. The patient ultimately required a near-total pancreatectomy due to the lack of response to pasireotide.
Interpretation
The results indicate that pasireotide may not be effective in improving glycemic control in this specific patient population, and its use could potentially worsen glycemic stability. This contrasts with prior expectations of improved insulin suppression based on its pharmacological profile. The limitations of this case report, including its single-patient design, suggest caution in generalizing these findings to broader populations.
Key findings
- Pasireotide was administered at doses of up to 0.11 mg/kg/day every 4 hours.
- Treatment did not lead to substantial clinical improvement.
- Increased glycemic variability was observed, with more frequent episodes of hypo- and hyperglycemia.
- Pasireotide was discontinued after 8 days due to lack of therapeutic response.
- The patient ultimately underwent near-total pancreatectomy.
Limitations
- Single case report limits generalizability.
- Short treatment duration of 8 days.
- No adverse effects reported, but safety data is limited.
- Lack of therapeutic response led to surgical intervention.