The World Health Organization has declared this century to be the century of autoimmune diseases. These include a whole spectrum of endocrine disorders, with type 1 diabetes mellitus, thyropathies, autoimmune polyglandular syndromes (APS), adrenal insufficiency and others, are among the most severe chronic non-infectious diseases in humans. Both the etiology and pathogenesis of autoimmune endocrinopathies are being actively studied, the concepts of the manifestation and progression of these diseases have already been formed, data on the genetic predisposition to one or another autoimmune damage to the endocrine system organs have been obtained, prenatal diagnosis of APD is being actively developed and introduced, attempts are being made to edit the genome in order to prevent their development. Despite this, there are still enough «white spots» in understanding the processes of induction and implementation of the mechanisms of autoimmunity in a particular person. The close connection of the immune and endocrine systems is obvious. The key question is: what is still primary, a genetic predisposition to «breakdown» of the immune system, leading to the development of an autoimmune endocrine disease, or some external influence that can cause direct damage to the endocrine organ (up to its destruction), leading in the end to the breakdown of immune tolerance and the launch of a cascade of autoimmune processes that aggravate an endocrine disorder? Modern advances not only in endocrinology, but also in immunology, molecular genetics, cell biology, etc. are absolutely necessary to clarify the relationship of immuno-inflammatory, hormonal and metabolic disorders in the pathogenesis of endocrine diseases at the cellular and molecular level and to develop new methods of prevention, early diagnosis, predicting the course and effectiveness of therapy for autoimmune endocrinopathies.

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II — to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm» in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

BACKGRAUND: Аutoimmune polyglandular syndrome (APS) it is characterized by damage to two or more endocrine glands, which eventually results in the hormonal failure. Some clinical studies describe the development of myocardial lesion in the setting of combined autoimmune endocrine pathology. In Russia the myocardial condition in adult patients with APS types 2 and 3 was examined for the first time.

AIM: To evaluate the structure and functional state of the myocardium according to magnetic resonance imaging (MRI), to analyze changes in the spectrum of specific antiheart autoantibodies and markers of heart lesion in patients with APS types 2 and 3.

MATERIALS AND METHODS: 50 patients with APS types 2, 3 were studied. 45 of them were performed with delayed contrast heart MRI. All 50 patients were tested for IgG antibodies to heart muscle antigens by indirect enzymatic immunoassay (EIA), for troponin I and natriuretic peptide by chemiluminescence immunoassay (CLIA), for creatine phosphokinase (CPK) by NAC (N – acetyl-L-cysteine), and for C-reactive protein (CRP) by immunoturbidimetry.

RESULTS: According to the results of heart MRI (n=45), 91% showed signs of functional changes in the left ventricular (LV) myocardium without any signs of myocarditis. 38 of 45 examined patients had deviation of 2 or more indicants of the LV functional state, M_EF 68.9±6.6%, IU_Mm — 86 [75; 99] g, IU_SV — 60.9 [50; 66] ml, IU_EDVi — 52 [44; 59] ml/m² , IU_ESVi — 17 [15.3; 18] ml/m² , IU_ESV — 26 [23; 31] ml, IU_EDV — 85 [70; 92] ml. 1 patient (2%) had positive result according to the determination of antibodies (AB) to heart muscle antigens (AG). Troponin 1 indicants did not exceed the reference values. The level of CPK exceeded the reference values in 3 patients (6%), an increase of CRP, NT-proBNP was observed in 7 patients (14%), and a combined increase was observed in 1 case.

CONCLUSIONS: We obtained MRI data indicating functional changes in the myocardium in patients with APS types 2 and 3. The autoimmune cause of these changes according to the results of determining of antiheart antibodies was not confirmed in most of the examined patients, the indicants of «damage» to the myocardium (troponin 1 and NT-proBNP) did not deviate from the reference range.

About 5–10% of malignant neoplasms (MN) are hereditary. Carriers of mutations associated with hereditary tumor syndromes (HTS) are at high risk of developing tumors in childhood and young age and synchronous and metachronous multiple tumors. At the same time, this group of diseases remains mainly an oncological problem, and clinical decisions are made only when MNs are detected in carriers of pathogenic mutations.

Individual recommendations for cancer screening, treatment, and prevention should be developed for carriers of mutations associated with HTS to prevent an adverse outcome of the disease. It is essential to identify patients at risk by doctors of all specialties for further referral to medical and genetic counseling with molecular genetic testing (in case of indications). The problems of standardization of enrollment criteria for genetic tests, further tactics of prevention, screening, and treatment of many hereditary oncological diseases remain unsolved.

This review was created to inform doctors of various specialties, including endocrinologists, about the HTS. This allows them to get acquainted with main clinical features of specific syndromes, helps to understand the difference between hereditary and non-hereditary cancer, recognize signs of hereditary cancer, and introduce the indications for genetic examination and genetic counseling of the patient. Also, significant differences between international and domestic recommendations on screening measures, diagnosis, and treatment of HTS underline the need to review the existing and develop new algorithms for medical support of patients with HTS.

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.

AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.

MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.

RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.

CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

One of the variants of congenital dysfunction of the adrenal cortex is a deficiency of the enzyme P450scc, which catalyzes the first stage of steroidogenesis. This is a rare autosomal recessive disease, the classic manifestation of which is primary adrenal insufficiency with a deficiency of gluco-and mineralocorticoids and a violation of the synthesis of sex steroids, which usually leads to a complete lack of masculinization in patients with karyotype 46, XY and hypergonadotropic hypogonadism in both sexes. Previously, it was suggested That p450scc deficiency is incompatible with the normal course of pregnancy, since the enzyme is expressed in the placenta, where it is necessary for the synthesis of progesterone, the main pregnancy hormone, and, consequently, the birth of a child with A p450scc deficiency is impossible. However, the literature describes clinical cases of p450scc deficiency with partially preserved enzyme function, which explains the normal course of pregnancy. Whereas cases of confirmed p450scc deficiency with zero enzyme activity are unique, not being explained until now. We present a description of severe p450scc deficiency in a child born from a dizygotic twin pregnancy in which the second Sib was healthy. It is possible that the preserved hormonal function of the second placenta and (or) treatment with progesterone analogs during gestation contributed to gestation in this rare form of steroidogenesis disorder.

RATIONALE: Continuous subcutaneous insulin infusion (CSII) is an effective method for optimizing glycemic control in children with type 1 diabetes mellitus (DM1). However, the use of CSII does not always result in adequate glycemic control. Telehealth can be applied as one of the methods to improve the effectiveness of treatment.

AIMS: To evaluate the use of remote medical support of children and adolescents with DM1 and its influence on glycemic control, quality of life, and incidence of acute complications of DM1.

MATERIALS AND METHODS: We conducted a 24-week multi-institutional prospective open-label controlled clinical trial. 180 children and adolescents were included in this study and divided into the following categories: 1) age 8–18 years; 2) DM1 at least 1 year; 3) pump insulin therapy Medtronic Paradigm (Medtronic MiniMed, USA) at least 6 months; 4) self-monitoring of glycemia at least 4 times a day and replacement of the insulin pump infusion system at least once every 3 days; 5) inadequate glycemic control of DM1: the level of glycated hemoglobin (HbA_1c) 7.5% or higher. Patients were assigned to a remote consultation group (RC; n=100) or a traditional control group (TC; n=80). All patients were trained on the basic principles of DM1 and CSII, and we measured initial HbA_1c, then after 12 and 24 weeks, also registered and analyzed glycemic indicators and daily doses of insulin, evaluated and corrected the treatment. Patients or their parents in the RC group sent pump data via the Internet to the pump insulin therapy center at least once every 2 weeks at home and received treatment recommendations in response.

RESULTS: The total number of patients included in the study in all institutions was 180 children at 8–18 years. Patients in both groups did not differ in age, gender, duration of DM1 and CSII, and HbA_1c level. The total amount of remote consultations for all institutions was 949. The decrease in the level of HbA_1c by the end of the study against the initial one was statistically significantly greater in the RC group: 1.17% compared to 0.59% in the TC group (p<0.05). The proportion of patients who reached the target level of HbA_1c (<7.5%) was significantly higher in the RC group (32%) compared to the TC group (12.5%, p<0.05). During the study, the incidence of DKA and severe hypoglycemia in the RC group was statistically significantly lower.

CONCLUSIONS: Remote monitoring in children with DM1 resulted in significant improvements in glycemic control (HbA_1c, glycemic variability, and hypoglycemic frequency). The accumulation of evidence on the effectiveness and safety of telehealth in DM should contribute to implementing this approach in practical health care.

Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.

The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.

RATIONALE: Insufficient world–wide clinical experience in radioiodine therapy (RIT) for Graves’ disease (GD) in children and adolescents, and limited knowledge of the predictors of RIT efficacy.

AIMS: Analysis and identification of the most significant predictors of the efficacy of RIT in children and adolescents with Graves’ disease.

MATERIALS AND METHODS: A total of 55 patients (48 females and 7 males) aged from 8 to 18 years receiving primary RIT for GD were enrolled. RIT planning was based on the dosimetric method. Analyzed parameters included gender, age, ultrasound thyroid volume before and 6 months after treatment, the presence of endocrine ophthalmopathy, duration of antithyroid drug (ATD) therapy, relapse of thyrotoxicosis after ATD dose reduction, blood fT3, fT4 and TSH levels initially and at 1, 3, 6 months after treatment, TSH receptor Ab initially and at 3 and 6 months after treatment, thyroid ^99mTc–pertechnetate uptake at 10–20 minutes (%), maximum thyroid ¹³¹I uptake (%), specific ¹³¹I uptake (MBq/g) and therapeutic ¹³¹I activity (MBq). Fisher exact test, non–parametric Mann–Whitney test, Wilcoxon signed–rank test, logistic regression modelling, ROC–analysis, proportional hazard model (the Cox regression), the Kaplan–Meier method and log–rank test were used for statistical analysis as appropriate.

RESULTS: Six months after RIT, hypothyroidism was achieved in 45 (81.8%), euthyroid state – in 2 (3.6%), and in 8 (14.6%) patients thyrotoxicosis persisted. On univariate statistical analysis, the smaller thyroid volume, higher fT4 and lower TSH receptor Ab levels, lower ^99mTc–pertechnetate uptake and higher specific ¹³¹I uptake were associated with hypothyroidism. On multivariate logistic regression analysis, the older patient’s age (p=0.011), smaller thyroid volume (p=0.003) and higher fT4 (p=0.024) were independent predictors of RIT efficacy. Thyroid volume was also the only variable associated with achievement of hypothyroidism in time after RIT (p=0.011).

CONCLUSION: The efficacy of dosimetry–based RIT in children and adolescents with GD 6 months after treatment was 81.2%. Older patients’ age, smaller thyroid volume and higher fT4 level were independent predictors of therapy success. Smaller thyroid volume was also a predictor of the favorable time–related outcome. Statistical models obtained in this work may be used to prospectively estimate the chance of efficient RIT for GD in pediatric patients.

The WHO has declared a SARS-CoV-2 pandemic. During a pandemic, the researches aimed at finding the new treatments for SARS-CoV-2 become relevant. The review focuses on studies of androgens and antiandrogens in this disease. Since the beginning of the COVID-19 epidemic, it has been noted that men have more severe forms of infection and higher mortality. The main cause of both the severity of the disease and the high mortality of men from COVID-19 are associated with androgens. It was found that patients receiving androgen deprivation are less likely to become infected and easily tolerate COVID-19. The researchers explain the effect of the therapy by the effect on the TMPRSS2 protein. It was found that both TMPRSS2 expression and a more severe course of coronavirus infection are observed in men with hyperandrogenism – androgenic alopecia, acne, excessive facial hair growth and increased skin oiliness. In this regard, some researchers suggest to use androgen deprivation for men at high risk of developing COVID-19. Steroid and non-steroidal antiandrogens are used for androgen deprivation. At the same time, obtaned scientific data on the relationship of severe forms and mortality of COVID-19 with low testosterone levels leads to a hypothesis about the possibility of a positive effect not of androgen devrivation therapy but of androgen replacement therapy in case of hypogonadism have diagnosed. These studies have not been completed recently, and data on the effectiveness and safety of antiandrogens and androgens in the treatment of a new coronavirus infection require clarification.

The publication of this article is undoubtedly a significant and positive phenomenon, while the initiative of the journal «Problems of Endocrinology» with the introduction of a new section «Oncoendocrinology» should be welcomed and will serve to unite the efforts of specialists of various profiles in the appropriate direction.