Thyroiditis in children are important issues of pediatric endocrinology due to their widespread occurrence. They differ in etiology, pathogenesis, and their clinical manifestations. Updated clinical guidelines in 2024 are the main working tool of physicians. They briefly and structurally present the main information about epidemiology and modern classification of thyroiditis, methods of diagnosis and treatment based on the principles of evidence-based medicine.

Today, the contribution of hereditary tumor syndromes to the development of cancer in children is obvious, which determines the need for screening programs and selection of the most effective methods of anticancer therapy. One of the most aggressive hereditary tumor syndromes is heritable TP53-related cancer syndrome (hTP53rc, formerly known as Li–Fraumeni syndrome), characterized by a high risk, early onset and recurrent cases of malignant neoplasms in one patient. The article describes current data on hTP53rc syndrome and the features of its clinical course, and provides international recommendations for monitoring and cancer screening in pediatric patients with hTP53rc syndrome. As a clinical observation, we present an analysis of the registry of patients with relapsed and refractory forms of medulloblastoma (n = 241) with the assessment of its incidence in cases of germline mutations in the TP53 gene with the description of their medical history and the influence of this genetic event on the outcomes. The results of our study, as well as data from international literature, indicate unfavorable prognosis in tumors, including medulloblastoma, in patients with hTP53rc syndrome, however, such factors as early screening, surveillance and early and adequate therapy can help to increase their life expectancy. The study was approved by the Independent Ethics Committee and the Scientific Council of the Almazov National Medical Research Centre of Ministry of Healthcare of the Russian Federation.

Endocrinology, one of the most dynamically developing branches of medicine, has existed as a separate discipline for a little over 100 years. The author of one of the first guidelines on endocrinology in Russia and the founder of the Leningrad School of Clinical Endocrinology was Professor Vasily G. Baranov (1899–1988). In 1926, an endocrinology department was opened at the Department of Therapy of the Leningrad State Institute for Advanced Medical Training under the leadership of Vasily Gavrilovich. Later, in 1963, Professor V.G. Baranov founded the Department of Endocrinology at this educational institution, which currently bears the name of the scientist. V.G. Baranov paid special attention to the issues of endocrine diseases in childhood. Together with academician A.F. Tur, he initiated the creation of an endocrinological service in pediatrics. It was only in 1998 that a new specialty “pediatric endocrinology” was added to the already existing training programs for doctors in the specialty “endocrinology”, opened by order of the Ministry of Health of the Russian Federation. However, the development and formation of pediatric endocrinology as a separate medical discipline took place before official recognition. A special role in the history of this formation belongs to the doctors of St. Petersburg.

Diagnostic and treatment facilities in pediatric oncology have reached a very technological advances in a short period of time, contributing to increased relapse-free and overall survival rates. Obviously, the key factors are the improvement of diagnostic and screening programs, anticancer and concomitant therapy, including personification of clinical guidelines for monitoring and correction of early and late complications in time. Issues regarding the quality of life of patients, including social, psychological rehabilitation and aspects of reproductive potential, are becoming highly actual. The critical importance is that an informed multidisciplinary team of specialists at all stages of anticancer treatment should be involved. This article presents the main algorithms and the most significant issues for pediatricians in the diagnosis and supervision of patients with an oncological diagnosis, using the example of medulloblastoma, as the most common malignant tumor of the central nervous system in children. The proposed recommendations are based on a retrospective analysis of pediatric patients with relapsed and refractory forms of medulloblastoma (n = 270) who received antitumor therapy in the period from 07/01/1993 to 07/01/2023, as well as international clinical data.

The etiology of precocious puberty includes organic anomalies, genetic mutations, but the primary cause remains unclear in the vast majority of cases. Gonadotropin-releasing hormone (GRH) agonists are used as a treatment of gonadotropin-dependent precocious puberty. Blocking the secretion of gonadotropin-releasing hormone, these drugs stop the premature development of sexual features, prevent premature closure of ossification zones, thereby increasing the child’s expected adult height. The interest in the effects of this group of drugs beyond the hypothalamic-pituitary-gonadal axis has been recently increased. A series of clinical cases have been reported on the development of autoimmune diseases, e.g., autoimmune thyroiditis, Graves disease and type 1 diabetes. The article presents a clinical observation of a patient with central form of premature development who exhibited satisfactory response to treatment with a GRH agonist drug. Further follow-up did not show any reproductive dysfunction. Upon immunological examination, a disturbance was revealed only in the cellular component of immunity. An increased metabolic activity of neutrophils was found, thus, probably, indicating a nonspecific inflammatory process. The levels of immunoglobulins A, M, G matched the reference values. Thus, the therapy with a drug from the group of GRH agonists was effective and safe in terms of influencing the patient’s immune system. The role of hormonal disorders and effects of GRH agonists on the development of immunopathological conditions require further research.

BACKGROUND. Hypoglycemia and fear of hypoglycemia remain critical problems in the treatment of adolescents with type 1 diabetes mellitus (DM1) and are factors limiting proper control of glycemia and preventing the achievement of metabolic compensation of the disease. The use of pump insulin therapy involves the prevention of hypoglycemic conditions. AIM. To analyze the frequency and duration of hypoglycemia episodes, their effect on the metabolic compensation of the disease in adolescents with type 1 diabetes mellitus (DM1) in real clinical practice, depending on the mode/method of insulin administration. MATERIALS AND METHODS. The study involved 117 adolescents with DM1 aged 12 to 19 years (average age 15.5 years). 37 adolescents received therapy by continuous subcutaneous insulin infusion (CSII); 80 adolescents received therapy by multiple insulin injections (MII). The level of glycated hemoglobin (HbA 1c ) was determined for all adolescents, and its main indicators were evaluated using a 6 days continuous glucose monitoring (CGM) by the «blind» method of a professional system with an iPro 2 sensor (Medtronic MiniMed, USA). RESULTS. Episodes of a decrease in glucose levels <3,9 mmol/l were recorded in 87% of patients (n=102), 63% (n=74) showed a decrease in glucose levels <3,0 mmol/l. Episodes decrease in glucose levels <3,9 mmol/l at night were recorded in 68% of patients (n=80), and with glucose levels <3,9 mmol/l in 46% (n=54). The frequency of episodes of glucose lowering <3,9 mmol/l had no statistically significant differences depending on the methods of insulin administration (by continuous subcutaneous insulin infusion or multiple insulin injections), however, they are more common in adolescents with HbA 1c <7,0% (p=0,03). The median time spent by patients in the range of <3,9 mmol/l was 5% per day, and a longer time in this range was observed in patients with HbA 1c <7,0% (p=0,006). The median time in the range of <3,0 mmol/l was 1% per day and had no significant differences depending on the level of HbA 1c (p=0,559). There were also no significant differences depending on the groups using CSII and MII (p=0,640 and p=0,250). CONCLUSION. Episodes of glucose reduction in the range of <3,9 mmol/l according to CGM data are more common in adolescents with HbA 1c target values, regardless of the method of insulin administration. Significantly more time in range of <3,9 mmol/l is spent by adolescents with target values of HbA 1c i.е. <7,0% compared with HbA 1c ≥7,0%, however, in both groups, a large number of patients had time in the range below the target level was higher than recommended values.

In addition to type 1 and 2 diabetes mellitus (DM), endocrine disorders in children include hereditary forms of diabetes, such as maturity onset diabetes of the young (MODY). Since pathogenic mechanisms of chronic hyperglycemia in MODY are different from those in DM1 and DM2, it requires other therapeutic approaches. The diagnosis of MODY is confirmed by expensive molecular testing, such as next generation sequencing (NGS). Therefore, the strategy of choosing candidates for NGS is very important. Objective. To optimize the algorithm of choosing patients for NGS testing for DM type verification. Patients and methods. This study included 97 patients aged 1–18 years suspected of having MODY. We used NGS to confirm the diagnosis and identify polymorphisms in MODY-associated genes. Results. Fifty-three patients were found to have polymorphisms in MODY-associated genes, including GCK gene (MODY2) (n = 44), NHF1A gene (MODY3) (n = 8), and PAX4 gene (MODY9) (n = 1). Comparison of family histories of patients with MODY-associated polymorphisms and those in whom clinical diagnosis of MODY was not confirmed by NGS demonstrated significant differences: children with verified MODY were more likely to have first-degree relatives with some carbohydrate metabolism disorder (CMDs). Clinical, laboratory, and anthropometric parameters, as well as levels of insulin secretion and carbohydrate metabolism were similar in both groups. However, patients with non-confirmed MODY received insulin therapy more frequently than those with verified MODY as the majority of them were on a diet. Conclusion. NGS confirms the diagnosis of MODY in patients with different CMDs. A tailored approach should be used to choose patients for NGS to confirm MODY. Key words: monogenic diabetes mellitus in children, diabetes mellitus, next generation sequencing, GCK, HNF1A, MODY

ВАРИАБЕЛЬНОСТЬ ГЛИКЕМИИ У ПОДРОСТКОВ С САХАРНЫМ ДИАБЕТОМ 1 ТИПА, ИСПОЛЬЗУЮЩИХ РАЗНЫЕ МЕТОДЫ ВВЕДЕНИЯ ИНСУЛИНАЦаргасова И .М ., Башнина Е

MODY С ВАРИАНТАМИ В НЕСКОЛЬКИХ ГЕНАХ-КАНДИДАТАХТуркунова М .Е 1 , Ворохобина Н .В . 1 , Башнина Е .Б . 1 , Берсенева О

Introduction: Floating Harbor syndrome (FHS) is an extremely rare disorder, with slightly more than a hundred cases reported worldwide. FHS is caused by heterozygous mutations in the SRCAP gene; however, little is known about the pathogenesis of FHS or the effectiveness of its treatment.Methods: Whole-exome sequencing (WES) was performed for the definitive molecular diagnosis of the disease. Identified variants were validated using Sanger sequencing. In addition, systematic literature and public data on genetic variation in SRCAP and the effects of growth hormone (GH) treatment was conducted.Results: We herein report the first case of FHS in the Russian Federation. The male proband presented with most of the typical phenotypic features of FHS, including short stature, skeletal and facial features, delayed growth and bone age, high pitched voice, and intellectual impairment. The proband also had partial growth hormone deficiency. We report the history of treatment of the proband with GH, which resulted in modest improvement in growth prior to puberty. WES revealed a pathogenic c.7466C>G (p.Ser2489*) mutation in the last exon of the FHS-linked SRCAP gene. A systematic literature review and analysis of available genetic variation datasets highlighted an unusual distribution of pathogenic variants in SRCAP and confirmed the lack of pathogenicity for variants outside of exons 33 and 34. Finally, we suggested a new model of FHS pathogenesis which provides possible basis for the dominant negative nature of FHS-causing mutations and explains limited effects of GH treatment in FHS.Conclusion: Our findings expand the number of reported FHS cases and provide new insights into disease genetics and the efficiency of GH therapy for FHS patients.

Central precocious puberty occupies an important place in the practice of a pediatric endocrinologist. If the patient reveals signs of premature sexual development, the diagnostic search is aimed at eliminating the tumor origin of both false (peripheral) and gonadotropin-dependent, or central, precocious puberty, as well as gonadotropin-independent forms of premature sexual development. Oncological alertness is important in the work of not only a pediatric endocrinologist, but also a pediatrician. In the treatment of all non-tumor forms of central precocious puberty, drugs of the group of analogues of gonadotropin-releasing hormone are used, which allows to stop the progression of sexual development, reduce the rate of bone maturation and, thereby, increase the final growth of the child. The most common idiopathic variant of central precocious puberty. The article presents a clinical case of observing a patient with an idiopathic variant of central premature sexual development during therapy with a drug from the group of analogues of gonadotropin releasing hormone of prolonged action. The classical course of the idiopathic variant of central precocious puberty with typical diagnostic difficulties in the onset of the disease, good compensation against the background of therapy with a drug from the group of agonists of gonadotropin-releasing hormone and normal puberty 612 months after cancellation of the therapy is demonstrated. The latter is explained by the proven reversibility of the effects of this group of drugs. The description of this clinical case, in the authors opinion, should be of interest to doctors at the local pediatricians and pediatricians working in the medical care departments for children in educational institutions.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.

The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

9312-13 июня 2021 г. РОЛЬ ПРИВЕРЖЕННОСТИ К ПОМПОВОЙ ИНСУЛИНОТЕРАПИИ ПРИ ДЛИТЕЛЬНОСТИ САХАРНОГО ДИАБЕТА 1 ТИПА БОЛЕЕ ТРЕХ ЛЕТИ.М.Царгасова, О

СБОРНИК ТЕЗИСОВ XVII Российская научно-практическая конференция детских эндокринологов «Достижения науки в практику детского эндокринолога» ЗНАЧЕНИЕ НЕПРЕРЫВНОГО МОНИТОРИРОВАНИЯ ГЛИКЕМИИ В ПОДДЕРЖАНИИ МЕТАБОЛИЧЕСКОЙ КОМПЕНСАЦИИ САХАРНОГО ДИАБЕТА 1 ТИПА У ДЕТЕЙ И ПОДРОСТКОВ И.М.Царгасова, Е