Clinical Efficacy Evaluation of Sirolimus in Congenital Hyperinsulinism
| Autor: | Reza Jafarzadeh Esfehani, Rahim Vakili, Amirhossein Sahebkar, Somayyeh Hashemian, Siroos Karimdadi, Daniel Zamanfar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Article Subject Endocrinology Diabetes and Metabolism medicine.medical_treatment Octreotide 030209 endocrinology & metabolism Hypoglycemia Gene mutation Asymptomatic Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences 0302 clinical medicine Endocrinology 030225 pediatrics Internal medicine medicine Genetic testing medicine.diagnostic_test Endocrine and Autonomic Systems business.industry RC648-665 medicine.disease Sirolimus Pancreatectomy Congenital hyperinsulinism Clinical Study medicine.symptom business medicine.drug |
| Zdroj: | International Journal of Endocrinology International Journal of Endocrinology, Vol 2020 (2020) |
| ISSN: | 1687-8345 1687-8337 |
| Popis: | Background. Congenital hyperinsulinism (CHI) is a rare and life-threatening genetic disorder. Sirolimus as a mammalian target of rapamycin inhibitor may be helpful in patients with CHI who do not respond well to other treatments including diazoxide and octreotide. However, the safety and efficacy of this therapy are still unclear. This study aimed to evaluate the potential therapeutic effects of sirolimus in CHI patients with mutations in the ABCC8 and KCNJ11 genes. Methods. During the period of this follow-up study, every child with a confirmed diagnosis of unresponsive CHI underwent genetic evaluation. Among those who had positive genetic testing, six families agreed to participate in this study. The participants were evaluated for ABCC8, KCNJ11, or HNF4α gene mutations by polymerase chain reaction (PCR) sequencing. The participants who were unresponsive to diazoxide and octreotide therapy received 0.5 mg/m2/d of sirolimus, and the dose was gradually increased until a serum concentration of 5–15 ng/ml was achieved. Then, the participants were followed up for any possible complications. Results. Among the study participants, only one neonate was completely free of hypoglycemia after one year of follow-up, whereas three others experienced a partial reduction in hypoglycemic episodes over six months. One neonate underwent pancreatectomy despite receiving sirolimus. The oldest participant with a mutation in the ABCC8 gene responded well to sirolimus therapy after surgery and remained asymptomatic for 18 months. Conclusion. This study suggested that sirolimus therapy needs further evaluation to determine which patients will benefit the most. The genetic basis of CHI may have possible implications for determining the patient’s response. |
| Databáze: | OpenAIRE |
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