BACKGROUND: Primary hyperparathyroidism  (PHPT), one of the most common endocrine pathologies, is associated with a higher incidence of cardiovascular diseases, in particular, those caused by endothelial dysfunction. Evaluation of endothelial dysfunction in patients with PHPT will predict the development of cardiovascular pathology and determine the optimal tactics for PHPT management.

AIM: To evaluate the concentration  of soluble endoglin  and photoplethysmographic parameters as potential markers of endothelial dysfunction in patients with PHPT.

MATERIALS AND METHODS:  A single-center interventional single-stage study was carried out. 2 groups were formed. The first group included 50 patients with verified PHPT who did not have cardiovascular or other concomitant somatic pathologies in anamnesis. The comparison group included 21 healthy volunteers comparable in sex and age. All participants underwent a biochemical blood test (total calcium, ionized, albumin, lipidogram, urea, uricacid, glucose, creatinine, alkaline phosphatase), parathyroid hormone, 25 (OH) D and endoglin concentrations were evaluated. In addition, echocardiography, ultrasound of the brachiocephalic arteries and arteries of the lower extremities, as well as photoplethysmography were performed.

RESULTS: The groups differed in mineral parameters associated with PHPT; no differences were found in parameters of lipid, uric acid and carbohydrate metabolism. Serum levels of endoglin  were lower in PHPT patients (p=0.002). We found a negative correlation between the concentration of albumin-corrected calcium and PTH with endoglin (r₁=-0.370, p₁=0.003 and r₂=-0.475, p₂<0.001, respectively) and a positive correlation between the concentration of endoglin  and phosphorus (r=0.363, p=0.003). These associations s were accompanied by changes in photoplethysmographic parameters that indicate an increase in the vascular wall stiffness.

CONCLUSION: The serum level of soluble endoglin  is lower in patients with PHPT than in healthy volunteers, negatively correlates with calcium and PTH concentrations and positively with serum phosphorus concentrations. Further studies will make it possible to establish the pathogenetic mechanism of the identified relationships and evaluate the role of endoglin as a potential predictor of cardiovascular pathology in PHPT population.

BACKGROUND: Increased consumption  of sweet and high-calorie foods leads to weight gain in humans and the development of metabolic syndrome. Great attention is given to a personalized approach to nutrition correction based on genetic testing. The genetic basis for human taste sensitivity to sweet stimuli remains is understudied. The role of the g.18853330 A>G (rs4920566) polymorphism of the TAS1R2 gene in preference for sweets has not been fully studied.

AIM: To investigate the possible relationship between rs4920566 polymorphism  in TAS1R2 gene and sensitivity to natural sugars and food preference of high-calorie sweet foods in humans.

MATERIALS AND METHODS: A single-sample experimental study was carried out. The study participants were conditionally healthy students who voluntarily agreed to conduct it. Sugar sensitivity was assessed in two tasting tests. Sucrose sensitivity thresholds (STS) were determined by staircase procedure (solutions: 8.0 to 500 mM/l). To assess food preferences for sweet foods, specially designed questionnaires with a checklist of products were used. Genomic DNA samples from all study participants were obtained from buccal epithelial cells. Genomic DNA was extracted from buccal epithelial cells using the adsorption of DNA with an inorganic sorbent in the presence of a chaotropic agent. Typing of the rs4920566 polymorphism in TAS1R2 gene was performed using asymmetric real-time PCR.

RESULTS: The study included  26 young  men and 110 young  women which the average age was 20.8±4.8 (SD) years. Gender  was  a  significant  factor  affecting  the  taste  perception  of  the  sweetness  sugars  (maltose,  glucose,  sucrose and fructose) in students. Young  men more often than young  women  could  not distinguish  the taste of four sugars (β=-2.93(0.99), p=0.003). The rs4920566 polymorphism in TAS1R2 gene did not affect the ability of students to distinguish the taste of four natural sugars. It was found that the variation series of STS values for sucrose in young women with the A allele (16.0[16.0–31.0] versus 16.0[8.0–16.0] mmol/l, p_cor=0.002) and A/G genotype  (16.0[16.0–31.0] vs. 16.0[8.0–16.0] mmol/l, p_cor=0.010) were significantly  lower compared to young men. Separately, in young women with the G/G genotype the range of STS is shifted towards higher concentrations of sucrose compared with women with the A/G genotype (16.0[16.0–31.0] vs. 16.0[8.0 -16.0] mmol/l, p_cor=0.039). Testing the hypothesis about the randomness of the relationship between the rs4920566 genotypes  of the TAS1R2 gene and the liking rating of foods with a sweet taste using Kruskal-Wallis test did not allow us to conclude that the A/A, A/G and G/G genotypes of the TAS1R2 gene influence the choice of sugary high-calorie foods in students.

CONCLUSION: Our results are consistent with the literature data and confirm that rs4920566 polymorphism of TAS1R2 gene cannot be an informative marker for the diagnosis of metabolic conditions associated with the consumption of high-calorie sweet foods. Likely, its functions are related to the mechanisms of neurotransduction of the sweet taste signal.

BACKGROUND: Patients with gout often take glucocorticoids  (GCs) and are at high risk of developing  type 2 diabetes mellitus (DM2).

AIM: Evaluation of the effect of long-term use of low doses of GCs on the risk of developing DM in patients with gout based on the results of a retrospective observation

MATERIALS AND METHODS: 317 out of 444 patients with gout and no DM2 who participated in a prospective study of risk factors for DM2 were included. The sample did not include patients who used GCs during  the observation period to relieve an acute attack of arthritis, regardless of the method of their use (n=88) and who did not complete the study (n=39). The remaining  patients were retrospectively divided  into 2 groups: those who continuously  took prednisolone  at a dose of 5-10 mg/day for ≥180 days and did not use GCs during the observation period. Scheduled visits were carried out at least once every 2 years. During  the 1st visit, patients were prescribed or corrected both urate-lowering and prophylactic  antiinflammatory therapy, including  low doses of GCs. The primary end point was the development of DM2, carbohydrate metabolism indicators (HbA1c  levels, serum glucose levels) were compared at baseline and at the end of the study.

RESULTS: Of 317 patients with gout, 76 patients (24%) were continuously taking prednisolone at a dose of 5-10 mg/day for ≥180 days, 241 patients (76%) did not receive GCs during  the entire follow-up period. The average dose of prednisolone in patients of the main group was 7.9±1.2 mg/day, the duration of treatment was 206.3±20.4 days.

DM2 developed  during  the observation period in 20% of the main group and in 22% of the comparison group (p=0.73). Patients who took GC were older than those who did not take GC (p=0.01), they were more likely to have CHF (p=0.04). There were no significant differences between the groups for the rest of the compared parameters. In patients treated with low doses of GC — a significant increase in the average level of HbA1c  (p=0.002); an increase in the number of patients with glucose levels ≥6.1 mmol/l (p=0.004) by the end of the study relative to the baseline. The initial level of HbA1c  in patients who developed DM2 was expectedly higher, among them smokers were more often detected (p=0.01), they had a higher level of serum UA (p=0.001). The prevalence of other risk factors for DM in those who developed and did not develop DM2 did not differ significantly.

CONCLUSION: Long-term use of low doses of GC in patients with gout does not significantly increase the risk of developing DM2, but may have a negative effect on carbohydrate metabolism.

BACKGROUND: According  to the results of the ESSE-RF study, the frequency of obesity in the population  reached 29.7%. Obesity is one of the main risk factors for the development of cardiovascular diseases. Features of the course of COVID-19 in patients with obesity is a very urgent problem.

AIM: The aim of the study was a comparative investigation of clinical and laboratory-instrumental parameters in AH patients with or without obesity who had COVID-19 associated pneumonia, to identify the role of obesity as a potential predictor of post-COVID cardiovascular complications 3 months after discharge from the hospital.

MATERIALS AND METHODS: Materials and methods. The study included 174 patients with COVID-19-associated pneumonia. Group 1 included 78 patients with AH without obesity, group 2 — 96 patients with AH and obesity. All patients were tested with a blood sample at the time of admission and 3 months after discharge from the hospital. We assessed parameters of general blood test, biochemistry, hemostasis, inflammation biomarkers — concentration of C-reactive protein (CRP), highly sensitive CRP (hs-CRP), homocysteine, IL-6, etc. All patients initially underwent computed tomography  of the chest. In both groups, 24-hour blood pressure monitoring was performed using BPLaB device, according to the standard protocol; echocardiography using  an expert class ultrasound diagnostic  system Vivid S70. The study is registered with the Clinical Trials.gov database Identifier: NCT04501822.

RESULTS: Results. The biomarker that significantly distinguished the both groups of patients, as well as subgroups according to the degree of obesity was the concentration of maxCRP and hs-CRP, which was significantly higher in group 2. In addition, the registered maximum values of MPO, NT-proBNP, IL-1,6, TNA-α and NRL parameters in group 2 of patients with 2–3 degrees of obesity, may indicate the highest probability of developing  delayed adverse cardiovascular complications  in this group of patients. Mean systolic blood pressure, variability of systolic and diastolic blood pressure, and heart rate at night were significantly  higher in AH patients with obesity. Numerous correlations of obesity with laboratory and instrumental parameters have been registered, which may indicate an increased likelihood of delayed unwanted cardiovascular complications in this particular group of patients. Multiple regression showed that obesity is an independent predictor of an increase in LDH, hs-CRP and right atrium.

CONCLUSION: Dynamic control of the studied parameters in patients with AH and OB registered an increased concentration of CRP at the initial stage and 3 months after treatment, with a general trend towards a decrease in the increased initial structural parameters of ECHO CG. The logistic regression method showed that the presence of OB in patients with AH is an independent factor causing increased levels of immune inflammation (CRP), a marker of tissue destruction (LDH), and load on the right atrium.

BACKGROUND: Metabolic syndrome currently continues to occupy a leading position in medicine and remains one of the main reasons for discussions among scientists around the world. WHO experts defined the problem of metabolic syndrome as an «epidemic of the 21st century», since its prevalence is currently, according to some estimates, from 10% to 40% among the adult population of the planet.

AIM: To study the metabolic syndrome in patients with arterial hypertension living in the Far North; to determine the main variants of the metabolic syndrome that are characteristic of people with arterial hypertension in harsh climatic and geographical conditions and to analyze the frequency of occurrence of the identified variants of the metabolic syndrome depending on the degree of arterial hypertension and gender differences.

MATERIALS AND METHODS. This study is presented in the form of 4 main stages: determination of metabolic syndrome variants characteristic of patients with AH living in the North, analysis of the frequency of occurrence of the identified main variants of the metabolic syndrome depending  on gender, degree of AH and time spent in the Far North. Study period: March 2018–February 2019.The main inclusion criteria for this study were: the presence of metabolic syndrome, a confirmed diagnosis  of arterial hypertension  (AH) of 1–3 degrees based on generally accepted  criteria (ESH / ESC, 2018), residence in the Far North for at least 1 year. For the diagnosis  of MS, the IDF criteria, 2005, were adopted. By design, the work is in the nature of an observational one-sample  study, which was conducted  in the Khanty-Mansiysk Autonomous  Okrug — Yugra, Nizhnevartovsk (KhMAO-Yugra).

RESULTS. The study involved 235 people, of which: men — 109 people (46.4±4,77%), women — 126 people (53.6±4,44%). The age of the study participants was 38±7.1 years. According  to the degree of AH (according  to the criteria, ESH / ESC from 2018), patients are presented as follows: 1st degree AH — 59 people (25.1± 2,83%); 2nd degree AH — 73 people (35.1± 3,11%);  3rd degree AH — 103 people (39.8± 3,19%). By the time of residence in harsh climatic conditions, all patients who took participation in this study were divided into three groups: group 1 — the residence time was from 1 year to 5 years. This group included 56 people (23.8±5,7%). 2 group — the period of stay in the Far North was from 6 to 11 years and this group is represented by 81 patients (34.5±5,3%) , group 3 — patients living in CS conditions for more than 11 years — 98 people (41.7±4,9%). № 1 — WC ≥ 94 cm in men and ≥ 80 cm in women + BP level ≥ 130/85 mm Hg + decrease in HDL cholesterol ≤ 1.03 mmol / L. This combination  of the main structural units of MS was observed in 43 +/-3.23% of cases (p<0.0016). Option number 2 — waist ≥ 94 cm in men and ≥ 80 cm in women + BP level ≥ 130/85 mm. rt. Art. + decrease in HDL-C ≤ 1.03 mmol/l + increase in triglycerides ≥ 1.7 mmol/l + increase in fasting glucose ≥ 5.6 mmol/l* — this combination of MS components occurred in 57+/-3.23 % of cases in all patients participating in the study (p<0.0011).

CONCLUSION. With an increase in the time spent in the Far North in patients with hypertension, who initially have a 3-component variant of the metabolic syndrome, there is a tendency towards an increase in the main components of the metabolic syndrome.

Endogenous  hypercortisolism  is a severe endocrine  disease characterized by prolonged  exposure to excessive amounts of glucocorticoid hormones, accompanied by a wide range of symptoms and complications, including immunosuppression. Timely surgical treatment in most cases allows to save the patient’s life, significantly improve its quality. However, restoration of the normal concentration of glucocorticoid  hormones can become a trigger factor in the development or exacerbation of autoimmune and auto-inflammatory diseases. We present a clinical case of atypical gout in a patient with hypercortisolism and a progressive increase in symptoms of the disease after successful surgical treatment for Cushing’s disease and achieving stable remission. The issues of diagnosis and treatment of this group of autoinflammatory diseases are highlighted, the leading clinical and radiological  symptoms are considered, the differential diagnosis  of microcrystalline (metabolic) arthritis is presented. Despite the widespread, the diagnosis and treatment of this group of diseases still cause difficulties for specialists. A competent choice of drug therapy allows to fully control diseases considered in the article, including when they are combined, and thereby improve the quality of life of the patient.

Obesity is a chronic pathology, which experts of theWorld Health Organization regard as an epidemic, based on the high rates of annual growth in the proportion of the overweight population in almost all countries of the world. Obesity is the leading cause of tissue insulin resistance and type 2 diabetes mellitus. This disease is fraught with serious complications: the onset and aggravation of cardiovascular pathology, non-alcoholic fatty liver disease, the appearance of certain types of malignant neoplasms and dysfunctions of the reproductive system. Adipose tissue, skeletal muscle and liver play unique roles in maintaining metabolic homeostasis of the whole organism. These differences are due to the tissue-specificity of the intracellular signaling  pathways of insulin. This review presents the current literature data on the features of the molecular mechanisms responsible for disturbances in the conduction of regulatory insulin signals at the intracellular level in its main target organs in obesity. The data on the nature of disturbances  in interorgan metabolic flows caused by the growth of adipose tissue mass and their participation in the formation of insulin resistance in the liver and muscles are presented. The importance of  further in-depth study of the tissue features of the mechanisms of insulin resistance pathogenesis  for the development of new targeted pharmaceuticals that will serve to improve the complex drug correction of metabolic disorders in patients with type 2 diabetes is discussed.

Over the years, immunotherapy with immune checkpoint inhibitors (ICI) has become an effective treatment for malignant neoplasms. However, checkpoints play a crucial role in immunological tolerance and prevention of autoimmune diseases. Interfering with this mechanism can cause immune-related adverse events (IRAEs) that affect multiple organs in the body. Endocrinopathies are among the most common IRAES associated with ICI therapy. Given the unique nature of adverse events caused by the use of ICI drugs, a multidisciplinary team approach is required to effectively manage patients, minimize complications associated with drug toxicity, and fully realize the therapeutic potential of this treatment method. Taking into account the difficulty of detecting nonspecific symptoms, the importance of follow-up and timely intervention in case of toxicity detection, regular clinical and laboratory monitoring is necessary, as well as informing patients and doctors about the variants of endocrine adverse events and their treatment. While non-endocrine IRAES often require discontinuation of immunotherapy and are usually resolved by immunosuppressive therapy with high doses of glucocorticoids, endocrine IRAES usually do not need discontinuation of ICI treatment and rarely require immunosuppressive therapy, but seldomly regress and therefore demand a long-term treatment.

Antipsychotic  drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations  due to neurological  disorders, depression with severe psychotic  symptoms. Metabolic disorders including  weight gain, dyslipidemia and hyperglycemia  are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations.

Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones  are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly  increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system.

It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics.

Patients with chronic obstructive pulmonary disease (COPD) are characterized by a variety of comorbid conditions, including both somatic (arterial hypertension, atherosclerosis, coronary heart disease, bronchial asthma, malignant  neoplasms, diabetes mellitus, obesity, etc.) and mental (depressive disorders, suicide attempts). Against the background  of various chronic diseases of the respiratory system, endocrine, metabolic disorders, the risks of exacerbations of COPD increase.

The leading  unifying  mechanism  of these conditions  is systemic subclinical  inflammation. Its excessive activity leads to the loss of the physiological functions of inflammation, which is accompanied  by an imbalance  in the endocrine system and the release of high concentrations of hormones and neurotransmitters. The result of this response is the uncoupling of cytokine mechanisms, which leads to an imbalance in the system of pro- and anti-inflammatory cytokines.

The article describes the role of the pro-inflammatory chemokine  IL-8 (interleukin 8), which is responsible for the migration of neutrophils to the site of inflammation. This is how the neutrophilic type of inflammation is formed. IL-4 and IL-10 are considered, which occupy a leading position in the formation of CD4+ type of immunoreactivity, which is observed in bronchial asthma. Attention is focused on the significance of IL-6, because it is an integral component of local and systemic inflammation. An increase in its concentration and, as a result, a potential risk of damage to the respiratory epithelium is the remodeling of the bronchial tree, resulting in a decrease in the elasticity of the epithelium of the respiratory tract. This mechanism leads to the formation of pulmonary emphysema and further potentiation of pathophysiological processes in patients with COPD.

Since IL-6 is a cytokine with anti-inflammatory  properties, its molecular activity is achieved by interacting  with a special receptor complex consisting  of two subunits: IL-6R and gp130. The former mediates IL-6 binding, while the latter triggers the JAK/STAT or MAPK signaling  cascade pathways. The result of the reaction of IL-6 with the effector cell directly depends on the type of signaling.

The paper describes three mechanisms of signal transduction into the target cell: classical, cluster, and transsignaling.

Thus, by studying  the role of cytokines in the systemic inflammatory response, we have shown the cross-talk between adipose tissue and the lungs in obesity, highlighting the main inflammatory mediators, which may indicate new therapeutic targets for preventing pulmonary dysfunction.