[The use of long-acting somatostatin analogs in congenital hyperinsulinism].

BACKGROUND: Children with congenital hyperinsulinism (CHI), a severe orphan disease, are still one of the most demanding patients in the endocrinology practice. The use of first- and second-line drugs is not always effective and has a number of restrictions. Lanreotide - long-acting somatostatin - represents an alternative insulinostatic therapy. The main advantage of lanreotide is stable concentration of the drug in the blood that enables minimizing the number of injections. However, the experience of using lanreotide in the treatment of CHI is limited to small groups of patients. There is also a problem of the absence of a standardized regimen in clinical practice; and the calculator for evaluating the initial effective drug dose is needed.AIM of the study is to evaluate the effectiveness and safety of lanreotide therapy in the treatment of CHI in children. MATERIALS AND METHODS: An open single-center observational study was conducted on the basis of Endocrinology Research Centre. The study included diazoxide-unresponsive pediatric patients with CHI who were initially treated with octreotide in different modes: multiple daily subcutaneous injections or continuous subcutaneous infusion via pumps. The indicators of the effectiveness and safety of the lanreotide therapy were evaluated shortly after the first injection and lately on a regular visit after further injections. RESULTS: The study group included 12 patients. Persistent euglycaemia was achieved in 67% of the subjects (8/12). Complete effectiveness of the therapy was observed in 8/12 patients (67%), partial - in 3/12 (25%), and lack of effectiveness - in 1/12 of the patient (8%). The age of the patients at the time of lanreotide administration was 6 months (5; 15). According to the study, the most effective dose of lanreotide is 3.5-5.5 mg/ kg/ month. There were no significant side effects observed. CONCLUSIONS: The use of lanreotide in patients with diazoxide-resistant congenital hyperinsulinism was effective and safe in the vast majority of the patients. Moreover, we were able to calculate the effective dosage of lanreotide in CHI patients which fulfilled the clinical demand.

[Clinical, genetic, and radionuclide characteristics of the focal form of congenital hyperinsulinism].

BACKGROUND: Congenital hyperinsulinism (CHI) is a severe disease with a high risk of complications including neurological deficit. Persistent hypoglycemia in patients with focal form of CHI can not be managed with medical treatment in 96.4% of cases, what subsequently leads to surgical treatment. Currently, there is a lack of information regarding patients with focal form of CHI. This study is aimed at finding better approaches for diagnosis and treatment of patients with focal form of CHI. AIMS: To study clinical, genetic and PET/CT findings of the focal form of CHI in Russian group of patients. MATERIALS AND METHODS: The observational research included all patients with a histologically confirmed focal form of CHI, who were admitted to Endocrinology Research Centre during the period from January 2008 to January 2019. A statistical analysis of clinical data, genotype, and positron emission tomography (PET) with 18F-dihydroxyphenylalanine (18F-DOPA) was performed. The median follow-up was 18 months. RESULTS: The study included 31 patients with focal CHI (14 boys, 45.2%). All patients had a neonatal presentation of the disease and demanded high levels of continuous glucose infusion to maintain euglycemia. The difference between the age of hypoglycemia presentation and the age of diagnosis ranged from 1 day to 3.9 months. In all cases, diazoxide was found to be ineffective. However, in 9 patients, it was possible to withdraw continuous glucose infusion and maintain euglycemia using octreotide in the preoperative period. A molecular genetic study allowed us to detect diverse pathogenic variants in ABCC8 and KCNJ11 genes in 30 patients. According to PET data with 18F-DOPA, the pancreatic index (PI) varied widely from 1.16 to 3.59. After partial resection of the pancreatic region with insulin hypersecretion, all patients showed complete recovery. CONCLUSIONS: The focal form of CHI is a severe condition with high prevalence of neurological complications. For preoperative diagnosis of the morphological form of the disease, it is necessary to conduct genetic analysis and radionuclide studies. Solely evaluation of mathematical parameters in 18F-DOPA PET without taking into account the visual data and the results of genetic analysis does not allow establishing the robust diagnosis. Timely diagnosis, identification of risk factors, and prevention of complications of persistent hypoglycemia are important tasks for clinicians.