Modern pediatric endocrinology represents the dawn of a new era in diagnosis and treatment, based on scientific research in molecular genetics and the development of advanced diagnostic and therapeutic tools. At the Pediatric Clinic of the En docrinology Research Centre (ERC), later the Institute of Pediatric Endocrinology, molecular genetic research began in 1990 in collaboration with the N.P. Bochkov Research Centre for Medical Genetics and the Institute of Immunology. The ERC’s Laboratory of Molecular Genetics has been operational since 2001, conducting research in partnership with foreign clinics and institutions.

BACKGROUND: Autoimmune diseases such as Graves’ disease are complex pathologies that often require intensive and long-term treatment. However, the mechanisms contributing to the development and maintenance of this pathology are still not fully understood. Understanding the role of the innate immune response, especially in the context of monocytes, in the development of Graves’ disease remains a poorly understood aspect.

AIM: To study the level of ROS production in monocytes in patients with Graves’ disease after RAI to identify the level of activation of the macrophage-monocyte system.

MATERIALS AND METHODS: The hormonal status and monocyte activity were analyzed before and 1, 3 and 6 months after RAI. The level of ROS was determined using spontaneous and luminol- and luceginin-derived chemiluminescence.

RESULTS: The study included 48 patients with Graves’ disease, aged from 18 to 65 years. In patients with Graves’ disease, a decrease in the intensity of free radical processes in monocytes was detected compared to the control group. These changes were observed both before and after RAI. It has been shown that changes in ROS production are independent of thyroid function and antibody levels. The changes indicate the potential immunosuppressive effects of radionuclide treatment and its effect on monocyte NADPH oxidase activity. A decrease in the production of secondary ROS in monocytes was also noted, which may indicate a decrease in the activation of monocytes during antigenic stimulation and inhibition of autoimmune processes.

CONCLUSION: Reduced metabolic activity of monocytes and low levels of ROS synthesis correlate with inhibition of the autoimmune process and decreased activation of the macrophage-monocyte system. The study confirms the importance of the role of monocytes in the ROS production system and their influence on the autoimmune process in Graves’ disease. These results may have clinical significance and contribute to the development of new immunotropic strategies for the treatment of this disease.

Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders characterized by defects in enzymes critical for steroidogenesis, with 21-hydroxylase deficiency due to mutations in the CYP21A2 gene being the most prevalent form.

Since the introduction of replacement therapy and neonatal screening programs in the 1950s, there has been a significant increase in survival rates among newborns diagnosed with CAH. However, despite these advancements, mortality associated with this condition remains disproportionately high. Achieving optimal therapeutic compensation through medication remains a complex challenge, contributing to a range of long-term complications. These complications stem from both the underlying disease and its treatment, impacting key physiological functions, including metabolism, growth and development, cardiovascular health, and fertility. These multifaceted outcomes underscore the need for ongoing research and the refinement of therapeutic approaches to better manage this intricate condition. This article presents a series of four clinical cases of CAH characterized by the absence of sustained compensation for glucoand mineralocorticoid deficiencies. These cases were further complicated by the development of large adrenal masses and ectopic testicular adrenal rest tissue (TART), emphasizing the challenges in achieving long-term disease management.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by autonomous secretion of parathyroid hormone by altered parathyroid glands. In most cases PHPT is a sporadic disease, 5-10% of observations are genetically determined syndromal and non-syndromal forms. Studies of families with hereditary forms of PHPT have led to the discovery of key oncosuppressor genes and proto-oncogenes whose somatic mutations underlie the development of many sporadic parathyroid tumors. Another interest in the pathogenesis of primary hyperparathyroidism is studying mechanisms of epigenetic regulation in tumor tissue. In the first part of this review, we will discuss the classification, morphology, and etiology of PHPT. In the second part, we will present a summary of the most important studies using genetic analysis, classified according to the method used.

BACKGROUND: Usually, a hypoglycemic episode occurs due to inadequacy of the administered insulin dose in accordance with the current physiological situation. Activated systems aimed at increasing blood glucose levels serve as precursors of hypoglycemia and markers of the severity of hyperinsulinemia. Therefore, determining their components can serve as a more subtle and sensitive approach to assessing the physiological appropriateness of different insulin therapy options.

AIM: To investigate the markers (biochemical, clinical, and morphological) and the degree of activation of the stress system preceding the development of hypoglycemic episodes in patients with type 1 diabetes (T1D) undergoing insulin therapy.

MATERIALS AND METHODS: A cross-sectional observational clinical study was conducted involving 74 patients with type 1 diabetes (T1D). All patients underwent examination, which included assessment of the history of hypoglycemic episodes, quality of life using the SF-36 questionnaire, levels of adrenocorticotropic hormone (ACTH), insulin-like growth factor-1 (IGF-1), cortisol, C-reactive protein (CRP), coagulation profile, and 24-hour urinary cortisol excretion. Evaluation of patients’ sleep characteristics was performed based on the results of completed questionnaires: Sleep Questionnaire and Epworth Sleepiness Scale. Patients underwent overnight polysomnography (PSG) with interpretation according to the AASM 2012 standards.

RESULTS: Patients with a higher frequency of hypoglycemic episodes showed a decrease in IGF-1 levels at all stages (140 [123:162]; 98 [93:121], p=0.005), worse quality of life scores across all domains of the SF-36 questionnaire (95 [88:100]; 84 [77:92], p=0.001). As the frequency of hypoglycemic episodes increased, polysomnography data revealed an increase in the number of awakenings lasting more than 3 minutes (2 [1:3]; 3 [2:4]; p=0.03), increased time spent in bed (493.1 [463.95:513.4]; 536.2 [511.6:551]; p=0.03), increased sleep duration (437.5 [430.05:468]; 489 [471.5:519], p=0.006), and in creased total sleep time (382.5 [321.75:422]; 439 [409.5:486], p=0.008).

CONCLUSION: An increase in the frequency of hypoglycemic episodes should be accompanied by activation of the stress response system; however, repeated episodes of hypoglycemia lead to depletion of the stress response system, as evidenced by a decrease in the level of IGF-1 in patients with frequent hypoglycemic episodes. Hypoglycemic episodes occurring not only during night time but also at other times disrupt the sleep structure by increasing the frequency of nocturnal awaken ings.

BACKGROND: The State Register of Diabetes Patients (SRDP) was first introduced throughout the Kyrgyz Republic in 2015 and has become one of the priority areas in the endocrinological service of the republic. The creation of a national registry was a significant step towards optimizing care for people with diabetes mellitus (DM). Currently, the register in the Kyrgyz Republic does not work online software, so all information about diabetes is assessed statically, representing a one-time snapshot for the end of the calendar year.

AIM: To study epidemiological aspects (prevalence,incidence mortality), as well as the frequency of complications of diabetes mellitus in Kyrgyzstan and the largest populated city in the country - Bishkek.

MATERIALS AND METHODS: The object of the study is the database of the DM register for the Kyrgyz Republic and the city of Bishkek (data over time from 2016–2023).

RESULTS: The total number of patients with diabetes registered in the dispensary in Kyrgyzstan as of 01/01/2024, according to the SRDP, was 85,142 people, which amounted to 1.2% of the total population of the republic. In Kyrgyzstan, according to the register, among patients with T1DM, the proportion of males was 52.4%, and females — 47.6%, and in the group of patients with T2DM, females predominated (59.9%). The prevalence of diabetes in the Kyrgyz Republic over the analyzed 8-year period (2016–2023) among patients with type 1 diabetes increased from 37/100ths of the population to 49.8/100ths of the population (1.35 times), and with T2DM — from 847.6/100ths population to 1159.0/100ths population (1.37 times). The dynamics of the annual incidence of T1DM in the Kyrgyz Republic averages 3.6 per 100ths population, and T2DM increased from 2016 to 2019, increasing by 27.6%, from 85 to 108.5/100ths population and decreased to 94/100 thousand population in 2023. The most common complications among patients with type 1 diabetes in the republic remain: neuropathy, retinopathy, nephropathy, and for type 2 diabetes — neuropathy, hypertension, retinopathy. According to the register, during the analyzed period there was a stabilization and/or decrease in the frequency of most diabetic complications, with the exception of stroke, diabetic foot (DF), and acute micardial infarction (AMI).

CONCLUSION: The SRDP in Kyrgyzstan, over 8 years of operation in static mode, has allowed for clinical and epidemiological monitoring, ensuring observation of patients from the moment of inclusion in the registry and providing data on the prevalence, incidence and complications of diabetes. However, the registry’s operation is hampered by the lack of access to the Internet and computers in a number of regions, as well as the timeliness of data entry. The transfer of the SRDP to an online format is necessary for effective monitoring and control of key disease indicators in real time.

Hepatogenic diabetes (HepD) is a form of diabetes where the primary pathogenesis is a liver disease, usually cirrhosis, complicated by the development of portal hypertension with the formation of porto-caval shunts. In the development of HepD, in addition to traditional risk factors for carbohydrate metabolism disorders, the pathogenetic features of liver diseases play a significant role. However, the exact mechanism of HepD development remains unclear, and several questions are still open for discussion. Despite having distinct pathophysiological and clinical features, hepatogenic diabetes is currently not considered as an independent disease. This is likely due to the difficulties in differentiating between types of diabetes due to the bidirectional relationship between glucose metabolism disorders and chronic liver diseases. It is known that diabetes negatively affects the development and progression of chronic liver diseases of various etiologies, and their combination is associated with worse clinical outcomes in terms of mortality, the occurrence of liver decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and the selection of optimal therapeutic strategies for diabetes may be challenging due to the lack of established clinical guidelines and the presence of comorbidities in patients with HepD.

Worldwide, the number of patients with diabetes has quadrupled over the past three decades. Every eleventh adult is currently diagnosed with diabetes mellitus, 90% of which are type 2 diabetes mellitus (DM2). Generally recognized complications of chronic hyperglycemia include micro- and macrovascular changes, damage to peripheral and/or autonomous nerve fibers. Scientists have also long discussed the relationship between an increase in the number of certain cancers and the presence of DM2. Based on the presence of common risk factors such as age, ethnicity, dietary habits and physical activity, many epidemiological and experimental studies are being conducted, which gradually contribute to understanding the relationship between these diseases. Taking into account the results of numerous studies, hyperglycemia, hyperinsulinemia and chronic inflammation, which are observed in DM 2, have a positive association with an increased risk of certain types of malignancies. In this article, the authors consider pathological changes in DM2 that potentiate the development of oncological diseases and epidemiological data reflecting the correlation between DM2 and the occurrence of malignant tumors.

The obesity epidemic is a major public health problem nowadays. The pathophysiology of obesity, which underlies its chronic, progressive, self-sustaining course, determines the difficulties in developing effective and safe methods for body weight control. The article is dedicated to the consideration of the evolution of conservative treatment of obesity, in particular, the history of pharmacotherapy of this disease, characterized by many ups and downs, is presented. The paper discusses, in chronological order, the emergence, efficacy, mechanisms of action, and described side effects of drugs that were investigated and used for weight loss at one time or another, as well as the reasons why many of them were subsequently withdrawn from the market. Until recently, long-term effective and safe pharmacotherapy of obesity remained an insurmountable challenge. Only in the last two decades has the understanding of the molecular mechanisms of appetite control reached a level that allows for a more productive search and development of promising drugs aimed at the pathogenetic treatment of obesity. This article discusses the status of currently available drugs for weight loss, as well as the prospects for drug treatment of obesity. The results of clinical trials of advanced therapeutic molecules, including gastrointestinal hormone receptor agonists, reinforce the belief that a breakthrough in the drug treatment of obesity is possible.

BACKGROUND: Primary hyperparathyroidism (PHPT) in children is quite rare, with a prevalence of 2–5 cases per 100,000 children. Hypercalcemia in PHPT has a negative impact on the gastrointestinal tract, urinary, musculoskeletal and nervous systems. Timely diagnosis of the disease in children is difficult due to its rare occurrence and variety of clinical symptoms.

AIM: To study clinical manifestations of primary hyperparathyroidism in children depending on the degree of hypercalcemia.

MATERIALS AND METHODS: Retrospective observational study with a prospective component 50 patients with primary hyperparathyroidism. All patients underwent a comprehensive laboratory and instrumental study at the Institute of Pediatric Endocrinology, Endocrinology Research Center of Russia in the period 2014–2023.

RESULTS: The clinical manifestations of primary hyperparathyroidism in children are very diverse. Weakness and fatigue were observed in 36% of patients (CI (23; 51)). Frequent manifestations of the gastrointestinal tract were nausea — in 20% (CI (10; 34)), gastritis — in 38%, (CI (25; 53)), duodenogastric reflux - in 24%, CI (13; 38). Hypercalciuria was detected in 64% of patients (CI (49; 77)), urolithiasis - in 36% (CI (23; 51). Complaints of leg pain were observed in 24% of patients (CI (13; 38)) deformity of the lower extremities was present in 20% (CI (10; 34)). 16% of patients had a history of low-traumatic fractures (CI (7; 29)). The median age of onset of the first clinical symptoms of PHPT in children was 13.7 years [10.6; 15.2]. At the time of diagnosis of the disease, 12 patients (24%) had no complaints and were examined due to incidentally detected hypercalcemia (n=3), hypercalciuria (n=1), and detected formations of the parathyroid gland according to ultrasound (n=5), with a family history of multiple endocrine neoplasia syndrome type 1 (n=3). To identify the relationship between the clinical manifestations of PHPT and blood calcium levels, all patients were divided into 3 groups depending on the level of hypercalcemia: mild hypercalcemia — 29 patients, moderate — 16, severe — 5. According to the results of the study, a statistically significant relationship between the presence of individual clinical manifestations of PHPT and the degree of hypercalcemia was not identified, however, a statistical tendency was noted between the presence of individual symptoms of the disease (hypercalciuria, weight loss, vomiting, pain in abdomen, constipation, esophagitis, rib pain, gait disturbance) and blood calcium levels, and a positive association was found between hypercalciuria and hypercalcemia. In addition, it was noted that in patients with severe hypercalcemia, the number of clinical signs is significantly higher than in patients with mild or moderate hypercalcemia.

CONCLUSION: The study demonstrates the variety of clinical manifestations of PHPT, for which doctors of various specialties — pediatricians, gastroenterologists, nephrologists, neurologists, orthopedic traumatologists, can observe children. In the presence of symptoms and diseases such as fatigue, nausea, pain in the legs, deformation of the lower extremities, low-traumatic fractures, urolithiasis, gastritis, it is necessary to examine the level of calcium in the blood in children.

Research in recent decades has shown a steady increase in the average life expectancy of humans, and women in particular. Any epithelial tissue reacts to changes in the surrounding hormonal environment in a similar way, but none of them can compare with the epithelium of the vaginal vault and cervix in terms of the speed and clarity of reaction to hormones, primarily sex steroids. The urogenital tract is especially sensitive to a decrease in estrogen levels, and about half of all women, both in reproductive age and during hormonal changes, may experience symptoms associated with vulvovaginal atrophy, affecting sexual health and quality of life. Estriol is the main estrogen that specifically addresses problems caused by estrogen deficiency: dyspareunia, dryness and itching in the vagina and lower genitourinary tract, urinary disorders, moderate urinary incontinence, as well as recurrent vulvovaginitis and cystitis. According to international and Russian clinical guidelines, the prescription of 0.5 mg is pathogenetically justified with a high level of persuasiveness and reliability. Vulvovaginal dystrophy in women of different ages is a multidisciplinary problem at the intersection of gynecology, urology and dermatology, which can and should be solved to prevent more severe gynecological and urological pathologies.