[Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19].

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. AIM: The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. MATERIALS AND METHODS: The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. RESULTS: The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. CONCLUSION: In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

[The problem of iodine deficiency in the Chechen republic: assessment of the current state and ways of solution].

Iodine deficiency disorders (IDD) are prevalent and highly morbidity, have hidden progression, severe disabling somatic complications, including cognitive disorders, reproductive losses, and oncopathology. This presents a serious challenge to the healthcare system of the Russian Federation, as it affects over 3 million people. The lack of relevant data on the severity of IDD and the current prevention programs at the regional level necessitates the need for appropriate research and measures in individual subjects of the Russian Federation. AIM: To conduct a comprehensive study to assess the current iodine security of the population of the Chechen Republic, to analyze the prevalence of thyroid pathology and compare it with official statistics, to formulate conclusions about the necessary preventive measures. MATERIALS AND METHODS: In the Chechen Republic, a total of 1239 people were examined, of which 921 were schoolchildren of pre-pubertal age (8-10 years) and 318 were adults. The survey of the adult population was carried out at medical organizations in four districts of the republic (Nadterechny, Shalinsky, Vedensky, Grozny) and included a questionnaire survey, a clinical examination by an endocrinologist with palpation of the thyroid gland, thyroid ultrasound, and a study by a qualitative method of samples of table salt used in households for the presence of iodine.Children's examinations were carried out by the cluster method on the basis of secondary schools in 9 out of 15 districts of the republic and included an examination by an endocrinologist and measurement of anthropometric parameters (height, weight), thyroid ultrasound to evaluate volume, determination of iodine concentration in single portions of urine and qualitative analysis of samples of table salt used in children's nutrition in families for the presence of iodine.The incidence and prevalence of thyroid disease among the population of the Chechen Republic were analyzed using data from official state statistics - form No. 12 «Information on the number of diseases registered in patients living in the area served by the medical institution¼ (ROSSTAT data as of 01.01.2021). RESULTS: According to the results of a survey of 921 pre-pubertal children, the median urinary iodine concentration was 71.3 µg/L (frequency of values below 50µg/L - 17,7%) and varies from 48.9 to 179.2 µg/L in the surveyed areas. According to thyroid ultrasound data, diffuse goiter was detected in 16.4% of the examined children, with goiter frequency ranging from 11.3% to 23.5%. The proportion of iodized salt consumed in schoolchildren's families was 4.2% in all study areas (range of values from 1.3% to 8%), which indicates an extremely low level of using iodized salt by household.According to the results of the examination of the adult population (n=318), structural changes in thyroid tissue were detected in 79.9% (n=254), while the proportion of nodular thyroid pathology being 83% (n=205), with a range of values across different districts of 52.5-80%. CONCLUSION: Based on the obtained data, according to WHO criteria, it can be stated that, overall, the degree of severity of iodine deficiency disorders in the Chechen Republic corresponds to mild severity with a tendency towards moderate severity in several districts of the foothills. The results of the examination of the adult population indicate a high prevalence of thyroid pathology, predominantly nodular, in the Chechen Republic. The data obtained in the course of large-scale research made it possible to initiate the development of necessary medical and organizational measures in the region - a program for the prevention of IDD.

[Dynamics the parameters of mineral metabolism in hospitalized patients with COVID-19, the impact of etiotropic and pathogenetic therapy].

The high prevalence of COVID-19 requires the research progress on the disease pathogenesis. There is a lot of data confirming the association between mineral metabolism and the severity of COVID-19. AIM: To study the dynamics of mineral metabolism parameters in patients with a confirmed COVID-19 at the time of hospitalization and after discharge, including the impact of etiotropic and pathogenetic therapy on them. MATERIALS AND METHODS: A single-center study of 106 patients (aged ≥18 years) with clinically or laboratory confirmed diagnosis of COVID-19 was carried out at the Endocrinology Research Centre, Moscow. Baseline biochemical parameters, including serum calcium, phosphorus, albumin, 25(OH)D, parathyroid hormone (PTH), inflammatory markers, and instrumental assessment of COVID-19 severity were performed before specific immunotherapy, as well as on 3rd and 7th days of hospitalization and before discharge. Statistical analysis was performed with Statistica 13 software (StatSoft, USA). RESULTS: On the first day, hypocalcemia (low albumin-adjusted calcium level) was detected in 40.6% of cases, the prevalence of vitamin D deficiency/insufficiency amounted to 95.3% of cases. At the same time, secondary hyperparathyroidism was identified only in 14.2% of patients. A comparative analysis of mineral metabolism during hospitalization (between 1, 3, 7 days of hospitalization and before discharge) during baricitinib treatment revealed a statistically significant increase in albumin-adjusted calcium by the end of hospitalization (p<0.001, Friedman criterion, Bonferroni correction p0=0.01). A pairwise comparison of subgroups, depending on the therapy, revealed a statistically significantly lower level of albumin-adjusted calcium on 3rd day among patients on baricitinib monotherapy or combined with tocilizumab compared with a subgroup of patients undergoing etiotropic treatment (2.16 [2.13; 2.18] mmol/l vs 2.23 [2.19; 2.28] mmol/l, p=0.002, U-test, Bonferroni correction p0=0.012). CONCLUSION: Patients with severe coronavirus infection are characterized by a high prevalence of vitamin D deficiency and hypocalcemia. Associations between calcium and saturation as well as the severity of lung lesion characterizes hypocalcemia as an important predictor of severe course and poor outcome in COVID-19. Pathogenetic therapy with baricitinib, including in combination with tocilizumab, contributes to achieve normocalcemia, but further studies are required.

[Determination of prolactin reference intervals in different age groups].

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed. AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the "expected prolactin levels" recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain). RESULTS: For adult men and women reference values were 66-436 and 94-500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the "expected values" of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both -cohorts. CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

[Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer].

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer. AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC. MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015-2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice. RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml. CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

[The role of systemic immune activation in the development of thyroid dysfunction in COVID-19].

BACKGROUND: The research of cytokine-induced thyropathies in the midst of continuing coronavirus infection (COVID-19) pandemic is a very important and urgent problem. On the one hand, COVID-19 is often accompanied by a massive overproduction of cytokines, so we can expect an enhanced cytokines effects impact on the thyroid gland. On the other hand, it is possible that biological therapy with tocilizumab, which has a powerful immunosuppressive effect, plays a protective role to the development of cytokines-induced thyropathies amidst COVID-19. The results of the study should be the starting point for understanding the mechanisms of possible compromise of thyroid function during COVID-19. AIM: The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, FT3 and FT4 values, and patient survival. MATERIALS AND METHODS: This retrospective, single-center study included 122 patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, FT3, FT4, antibodies to thyroid peroxidase, antibodies to the TSH receptor (AT-recTSH). The markers of the inflammatory process were assessed: interleukin-6, C-reactive protein, the degree of lung tissue damage according to multispiral computed tomography of the lungs, the percentage of blood oxygen saturation (SpO2), the treatment outcomes. RESULTS: Five (4%) patients were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with interleukin-6 (r=-0.221; p=0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p=0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. CONCLUSION: Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. This study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate.

[Adipokines and the cardiorespiratory system in young patients with type 1 diabetes mellitus].

Early screening of complications of diabetes mellitus (DM) is one of the priorities for public health. Most patients with type 1 diabetes mellitus (T1DM) are patients of working age. New strategies for the primary prevention of cardiovascular disease (CVD) are needed to prevent their early disability. AIM: To assess the predictive value of adipokines in relation to a personalized approach to the need for an in-depth examination of young patients with T1DM. MATERIALS AND METHODS: The study included 98 patients without CVD: 70 patients with T1DM (mean age 26.4±8.1 years) and 28 patients without DM (mean age 27±9 years). All patients underwent a general clinical examination, the levels of adipokines were determined, ergospirometry, echocardiography, and bioimpedancemetry were performed. RESULTS: Changes in the cardiorespiratory system in patients with T1DM were revealed, in comparison with persons without T1DM: anaerobic threshold was reached faster (p=0.001), maximum oxygen consumption was lower (p=0.048), metabolic equivalent was reduced (p=0.0001). Signs of myocardial remodeling were found in the T1DM group: there was an increase in the relative wall thickness (p=0.001), the posterior wall of the left ventricle (p=0.001), myocardial mass index (p=0.049), in comparison with persons without T1DM. Changes in the adipokines system were revealed: higher levels of resistin (p=0.002) and visfatin (p=0.001), lower level of adiponectin (p=0.040) in T1DM. A positive correlation was found between posterior wall of the left ventricle and visfatin (p=0.014) and a negative relationship between adiponectin and relative wall thickness (p=0.018) in T1DM. CONCLUSION: In T1DM, even at a young age, there are multifactorial changes in the heart, which can be detected even at the preclinical stage. The data obtained can be used to identify groups of patients at high risk of developing dangerous CVD in T1DM, which can form the basis for determining the timing of the start of preventive therapy.

[Reference intervals of thyroidstimulating hormone in pregnant women living in the central regions of the Russian Federation].

BACKGROUND: Pregnancy is a condition with important structural and physiological changes in the thyroid gland. In this regard, experts of thyroid associations have recommended developing specific reference intervals taking into account the natural and socio-geographical characteristics of the region under study. AIM: To conduct an epidemiological analysis and evaluate TSH reference intervals in pregnant women living in the central regions of the Russian Federation with mild iodine deficiency. MATERIALS AND METHODS: We have conducted the observational multicenter cross-sectional study included 2008 healthy pregnant women at different trimesters of pregnancy, from three regions of the Russian Federation (Moscow, Ivanovo and Smolensk). We assessed the level of thyroid-stimulating hormone, antibodies to thyroid peroxidase, antibodies to serum thyroglobulin, the level of iodine concentration in the morning portion of urine (cerium arsenic method) and we have conducted a questionnaire (date birth and gestational age). Women with elevated titers of anti-TPO and/or anti-TG antibodies were excluded from the study (245 women). As a result, we assessed high and medium levels of TSH and its overestimation with iodine sufficiency in pregnant women. The results are presented using the calculation of 2.5 and 97.5 percentiles. RESULTS: We confirmed the presence of iodine deficiency in the study areas. The median concentration of iodine in the urine was: in Moscow 106 µg/l, in Ivanovo 119 µg/l, in Smolensk 134 µg/l. Pregnant women were divided into 2 groups according to iodine adequacy. In the group with optimal iodine supply, the level of TSH was 0,006-3,36 in the 1st trimester, 0,20-3,74 in the 2nd trimester, and 0,33-3,68 mIU/L in the 3rd trimester. In the group with mild iodine deficiency - in the 1st trimester it was 0,11-3,00, in the 2nd trimester 0,22-3,78, in the 3rd trimester 0,07-3,04 mIU/l. Statistical analysis of the data revealed that when comparing the level of TSH by trimester, depending on the place of residence, no statistical difference was found (p = 0,239). CONCLUSION: We obtained that the level of TSH in healthy pregnant women living in the central regions of the Russian Federation does not exceed 3.8 mIU/l in all trimesters.

[The study of blood serum trace elements in comparison with the structural and functional characteristics of goiter and the carriage of antithyroid antibodies in some regions of Russia].

The study of the sufficiency with essential trace elements in the context of thyroid pathology is especially relevant, since the development and progression of thyroid diseases have various pathogenetic mechanisms, which largest proportion is provoked by insufficient intake of key trace elements, primarily iodine. The aim of the research was obtaining primary data on the sufficiency with essential trace elements of the population in the some regions of the Russian Federation, comparing the data obtained with the prevalence of goiter and the carriage of antibodies to thyroid peroxidase (AT-TPO). Material and methods. The Cross-Sectional Population Study was conducted in medical institutions of the Republics of Crimea, Republics of Tuva and Bryansk region (persons applied for outpatient consultations). The scope of the study was 387 people aged 18 to 65 years (the average age was 40±5 years). All of them underwent: collection of medical history, endocrinologist examination with palpation of the thyroid gland (TG), ultrasound examination of TG, blood sampling to assess the levels of thyroid-stimulating hormone (TSH), AT-TPO, iodine, selenium, zinc. Ultrasound of the TG was performed in the supine position using a portable ultrasound machine LOGIQe (China) with a multi-frequency linear probe 10-15 MHz. During the study, the volume of the thyroid gland, the presence of nodular formations and their characteristics according to the TIRADS classification, TG structure and its echogenicity were assessed. Iodine, selenium and zinc level were measured using tandem mass spectrometry with ionization in inductively coupled plasma (Agilent 8900 ICP-MS Triple Quad). TSH and Ab-TPO were determined by chemiluminescent immunoassay on the Architect i2000 automatic analyzer. Results. All regions are comparable in terms of iodine availability, but differ in the severity of natural iodine deficiency. The median concentration of iodine in blood serum practically coincided in all three regions, amounting to 39.8 µg/l in the Republic of Crimea; 38.8 µg/l in the Republic of Tyva and 43.4 µg/l in the Bryansk region. Comparing these results with foreign data, as well as with our results on urinary iodine level, obtained by routine cerium-arsenite method, we can assume that iodine content in blood serum corresponded to the lower limit of the normal target values. The median concentration of selenium in blood serum also practically coincided in all three regions, amounting to 68.2, 72.1 and 62.8 µg/l, respectively, and probably meets the criteria for optimality. The median serum concentration of zinc in Bryansk region residents corresponded to a deficiency (491.3 µg/l) and was significantly lower compared to the indicator in the Republics of Crimea and Tyva (1633.2 and 1667.6 µg/l, respectively, values above optimal). Among the examined, the proportion of people with AB-TPO carriership was 23.5% (Republic of Crimea - 20.9%, Republic of Tuva - 26.4%, Bryansk region - 20.7%), with impaired thyroid function - 9.6% (6.2% - hypothyroidism, 3.4% - thyrotoxicosis). The frequency of goiter varied from 10 to 13.8%. There were no significant differences in the frequency of occurrence, ultrasonic characteristics of goiter and thyroid nodules by regions. Conclusion. However, the results obtained do not allow to unequivocally judge the absence of micronutrient deficiency in the population of the regions of the Russian Federation, since used the ICP-MS method requires the development of our own reference values of trace elements; in the absence of the latter, data from similar foreign studies were taken as standards. In addition, in further studies it will be important to take into account additional criteria for assessing trace element deficiency, for example, activity of superoxide dismutase and alkaline phosphatase as indirect markers of zinc deficiency, etc. Correlation between blood serum concentration of trace elements and the frequency and structural characteristics of goiter, the carriage of Ab-TPO, and dysfunction of the TG was not revealed.

[Iodine Deficiency Disorders: Current State of the Problem in the Bryansk Region].

BACKGROUND: The Bryansk region is one of the regions of the Russian Federation most affected by the accident at the Chernobyl nuclear power plant on April 26, 1986.In the conditions of a chronic uncompensated deficiency of iodine in the diet in the first months after the accident, an active seizure of radioactive iodine by the thyroid tissue took place, which inevitably resulted in an increase in thyroid diseases from the population in the future. The article presents the results of a control and epidemiological study carried out in May 2021 by specialists of the National Medical Research Center of Endocrinology of the Ministry of Health of Russia, aimed at assessing the current state of iodine provision in the population of the Bryansk region. AIM: Assessment of iodine supply of the population of the Bryansk region. MATERIALS AND METHODS: The research was carried out in secondary schools of three districts of the Bryansk region (Bryansk, Novozybkov and Klintsy).The study included 337 schoolchildren of pre-pubertal age (8-10 years), all children underwent: measurement of height and weight immediately before the doctor's examination, which included palpation of the thyroid gland (thyroid gland); Thyroid ultrasound using a portable device LOGIQe (China) with a multi-frequency linear transducer 10-15 MHz; determination of iodine concentration in single portions of urine. A qualitative study for the presence of potassium iodate in samples of table salt (n = 344) obtained from households and school canteens was carried out on the spot using the express method. RESULTS: According to the results of a survey of 337 pre-pubertal children, the median urinary iodine concentration (mCIM) is 98.3 µg / L (range from 91.5 to 111.5 µg / L, the proportion of urine samples with a reduced iodine concentration was 50.1%). According to the ultrasound of the thyroid gland, 17% of the examined children had diffuse goiter, the frequency of which varied from 9.4 to 29% in the areas of study. The share of iodized salt consumed in the families of schoolchildren in the study areas was 17.8% (values range from 15.6 to 19%), which indicates an extremely low level of iodized salt consumption by the population. All salt used for cooking in school canteen areas of the study was iodized, which confirms compliance with the requirements of SanPiN 2.4.5.2409-08. CONCLUSION: Despite the active implementation in the Bryansk region of various preventive programs of IDD and social activities to promote the use of iodized salt, in the absence of mass prevention with the help of iodized salt to date, their unsatisfactory results should be noted.

[Clinical practice guidelines "Management of iodine deficiency disorders"].

Iodine deficiency disorders is a sweeping term that includes structural and functional impairment of the thyroid gland.These clinical guidelines include algorithms for the diagnosis and treatment of euthyroid goiter and nodular/ multinodular goiter in adults and children. In addition, these clinical guidelines contain information on methods for an adequate epidemiological assessment of iodine deficiency disorders using such markers as the percentage of goiter in schoolchildren, the median urinary iodine concentration, the level of neonatal TSH, the median thyroglobulin in children and adults. As well from these clinical guidelines, you can get to know the main methods and groups of epidemiological studies of iodine deficiency disorders.

Analytical platforms Vitros ECi 3600 and Cobas 6000: comparative analysis of prolactin measurement.

Prolactin is a polypeptide hormone secreted by the lactotrophic cells of the anterior pituitary gland and has a wide range of biological effects in the human body. Accurate measurements of prolactin concentration are essential in obtaining biochemical data to support clinical decisions in the diagnosis, treatment and prevention of diseases of the pituitary gland, reproductive, immune and other body systems. The aim of our study is to carry out a comparative analysis of the serum prolactin measurement determined by the two analytical platforms Vitros ECi 3600 (Ortho-Clinical Diagnostics) and Cobas 6000 (Roche). Serum samples from 664 patients undergoing examination at the Endocrinology Research Center were included in the study. Comparative analysis of serum prolactin measurement showed that results obtained by the two analytical systems are consistent with each other (r = 0.89, p<0,05). Clinically accuracy of prolactin measurement and to a large extent using the same method is of particular importance in primary diagnosis, treatment and long-term follow-up of the patient.

[Monitoring of iodine deficiency disorders in the Republic of Tyva].

BACKGROUND: The Republic of Tyva is a region with a proven severe natural iodine deficiency and a high prevalence of IDD (iodine deficiency disorders). However, in the region in certain periods of time, measures were taken to eliminate iodine deficiency in the diet of the population. The article presents the results of the October 2020. by specialists of the Endocrinology Research Centre, a control and epidemiological study aimed at assessing the current state of iodine supply in the population of the Republic of Tyva. The study was carried out on behalf of the Ministry of Health of Russia within the framework of the state task «Scientific assessment of the need to take additional regulatory legal and other measures to eliminate iodine deficiency in pilot regions with severe iodine deficiency¼. AIM: Assessment of iodine supply of the population of the Republic of Tuva. MATERIALS AND METHODS: The research was carried out in three settlements of the republic - years. Kyzyl, Shagonar, Saryg-Sep settlement. A total of 227 pre-pubertal schoolchildren (8-10 years old) were examined with anamnesis collection, examination by an endocrinologist, palpation of the thyroid gland, collection of single urine samples into disposable eppendorfs, followed by freezing to minus 20-25 degrees to further determine the concentration of iodine in urine with using the cerium-arsenitic method in the laboratory (clinical diagnostic laboratory of the Federal State Budgetary Institution «National Medical Research Center of Endocrinology¼ of the Ministry of Health of Russia). In addition, all schoolchildren underwent an ultrasound examination of the thyroid gland (using a portable ultrasound machine LOGIQe (China) with a multifrequency linear transducer 10-15 MHz, in the supine position). The height and weight of children was determined according to the standard method at the time of the examination. A collection of samples of edible salt, which is used in families of schoolchildren, was carried out and the presence of iodine in it was determined by an express method for the qualitative determination of potassium iodate.Parents of schoolchildren signed informed consent for the examination of children. Permission of the local ethical committee of the Endocrinology Research Centre - received, date: March 25, 2020, N 5. RESULTS: 227 schoolchildren of 8-10 years old were examined. The median concentration of iodine in urine was determined, the presence of iodine in food salt was investigated, and an ultrasound examination of the thyroid gland was carried out in order to clarify the iodine supply, the coverage of the use of iodized salt in nutrition and the prevalence of goiter.The median concentration of iodine in urine was 153 µg/l, the frequency of goiter was 7.7%, and the proportion of households using iodized salt was 95.2%. CONCLUSION: Results of assessment (median urinary iodine concentration) confirm that population of Tuva, Russian Federation, has optimum iodine nutrition. The prevalence of goiter in schoolchildren significantly decreased compared to earlier assessments. The proportion of households using iodized salt indicates the effectiveness of preventive measures in the -region.

[Obesity without diabetes: the role of hormonal regulation].

AIM: Obese patients without diabetes present an interesting phenotype to explore protective mechanisms against type 2 diabetes (T2D) development. In our study we looked for specific hormonal features of obese patients without T2D. MATERIALS AND METHODS: We included 6 groups of patients with different metabolic profiles (n=212): controls with BMI25 kg/m2, HbA1c6%, age 30 years; patients with 25BMI30 kg/m2and HbA1c6%; patients with 25BMI30 kg/m2and HbA1c6%; patients with BMI30 kg/m2and HbA1c6% (+ Obesity - T2D) obese patients without T2D or prediabetes; patients with BMI30 kg/m2and newly-diagnosed T2D/prediabetes, HbA1c6%; patients with known history of T2D on glucose-lowering drugs with BMI30 kg/m2. Insulin, GLP-1, GIP were measured during glucose-tolerance test at 0, 30 and 120 minutes; insulin resistance (IR) was assessed by HOMA-IR. RESULTS: Waist circumference was bigger in patients with obesity despite their metabolic profile comparing to patients without obesity (p0.001). Waist-to-hip ratio was similar in patients with different metabolic status. According to IR + Obesity - T2D group had intermediate position: IR was higher in that group comparing to people without obesity, but was less that in patients with obesity and HbA1c6% (p0.001). + Obesity - T2D group had the most potent baseline insulin secretion, assessed by НОМА-%band the highest postprandial secretion, measured by insulinogenic index among all patient groups with obesity (p0.001). There was no significant difference in GLP-1 secretion; GIP secretion was higher in patients with BMI30 kg/m2comparing to people with BMI30 kg/m2(p0.01).

[Dynamic changes of renin-angiotensin-aldosterone system parameters after surgery of primary hyperparathyroidism].

AIM: To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE). MATERIALS AND METHODS: A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity PRA, serum aldosterone, angiotensin II AT II). RESULTS: Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090;p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed. CONCLUSION: In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.

[Autoantibodies, immunoglobulins and cytokine profile in patients with graves' disease and Graves' orbitopathy].

BACKGROUND: Graves' Orbitopathy (GO) - also known as Thyroid Eye Disease (TED) - is an autoimmune condition in the modern sense. It is closely associated with autoimmune thyroid diseases. Cytokine-mediated mechanisms play a critical part in immunopathogenesis of autoimmune thyroid diseases including GO. Investigating cytokine profiles as well as antibodies to tissue-specific antigens is essential for explaining GO pathogenesis and developing future therapeutic strategies. AIMS: The study examines serum levels of cytokines, autoantibodies and immunoglobulins IgG and IgG4 as mediators of autoimmune inflammation in patients with GO and Graves' Disease (GD). MATERIALS AND METHODS: The study included 52 patients (104 orbits) aged 25-70 years (mean age 48,8±12,3) in the active phase of GO and GD verified with the international diagnostic standards. These patients did not get any treatment for GO before. The control group consisted of 14 individuals (28 orbits) aged 30-68 years without known autoimmune disease.Serum levels of IgG, IgG4,TNFα, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-13, sIL-6R, sTNFα- RI и TNFα- R2 IL-2R, TGFß1, TGF ß3, antibodies to TSH-receptor, free T4, free T3 and TSH were measured. A diagnostic ultrasound exam of thyroid gland, multislice computed tomography (MSCT) / magnetic resonance imaging (MRI) of orbits were performed. RESULTS: Mean duration of GO prior to being admitted to the centre was 8,8±1,5 months (range: 1 - 48 months). According to the degree of thyrotoxicosis compensation: 24 patients were clinically euthyroid, TSH 3,3±0,7 mU/L, free T4 11,9±0,59 pmol/L, free T3 3,97±0,1 pmol/L; 28 patients were considered to have subclinical thyrotoxicosis: TSH 0,03±0,01 mU/L, free T4 14,2±1,0 pmol/L, free T3 5,77±0,49 pmol/L. Serum levels of sTNFα-R2 (p=0,041, p≤0,05), sIL-2R (p=0,020, p≤0,05), TGFß1 (p=0,000, p≤0,001) were significantly higher in patients with GO compared to the control group. Serum levels of sTNFRα2 (p=0,038, p<0,05) and TGFß1 (P=0,011, p≤0,05) were positively correlated with the duration of GO. The positive correlations between the serum level of sIL-6R (p=0,034, p≤0,05) and the severity of GO as well as between the serum level of sTNFα- R 1 (P=0,012, p≤0,05) and activity of GO were observed. 54% of patients had elevated concentration level of IgG4 in IgG ( >5%). CONCLUSION: High levels of soluble cytokine receptors sTNFα-R2 and sIL-2R and cytokine TGFß1 in patients with long-standing untreated GO and GD being euthyroid or having subclinical thyrotoxicosis indicate activation of regulatory T cells aimed at suppressing autoimmune processes. High concentration level of IgG4 in IgG and cytokine TGFß1 can determine the development of fibrotic changes in the orbital tissues. A decrease in the concentration of cytokine TGFß1 can indicate an unfavorable course of the disease GO.

[Vitamin D and pregnancy: current state of the problem in the central regions of the Russian Federation].

BACKGROUND: It has been proven that vitamin D plays an important role in pregnancy. Deficiency of this element may be associated with the risk of developing gestational diabetes mellitus, preeclampsia, placentar insufficiency, low birth weight and premature birth. AIMS: To conduct an epidemiological analysis of vitamin D supply in women at different stages of pregnancy, living in Russia. MATERIALS AND METHODS: We included 1198 pregnant women living in 3 regions of Russia in the observational, multicenter, cross-sectional, continuous study. All pregnant women were tested for serum 25(OH)D levels. We collected biomaterial from August 2018 to December 2019. The end point of the study was the indicator of vitamin D supply in pregnant women and its level depending on the trimester of pregnancy and region of Russia. Statistical analysis included counting and grouping according to vitamin D levels, and calculating the median vitamin D concentration in each region. RESULTS: We confirmed vitamin D deficiency in all regions. The optimum level of this element is present in less than 7% of women. Insufficiency of this element is present in 20,62% of all women. The largest percentage of them is in a deficit of this element - 46,66%. We found that the lowest rates are in Smolensk, where the median was 12,75 ng/ml. In addition, we found changes in vitamin D concentration: with an increase in gestational age revealed a decrease in its level. CONCLUSIONS: In our study, we confirmed the presence of a 25(OH)D deficiency in most of the examined pregnant women, which is consistent with international epidemiological data. We should remember about these both at the stage of pre-gravid preparation and at the stage of pregnancy itself in order to achieve the optimal level of vitamin D.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

[A 20-year prospective follow-up study to evaluate the development of retinopathy and nephropathy after the onset of type 1 diabetes mellitus: Contribution of glycemic control and metabolic memory]. / Prospektivnoe 20-letnee nabliudenie, otsenivaiushchee razvitie retinopatii i nefropatii ot momenta debiuta sakharnogo diabeta 1-go tipa: vklad kontrolia glikemii i 'metabolicheskoi pamiati'.

AIM: To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). SUBJECTS AND METHODS: A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. RESULTS: During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. CONCLUSION: The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

[Evaluation of markers for renal graft dysfunction in patients with type 1 diabetes mellitus after kidney transplantation and simultaneous pancreas-kidney transplantation]. / Otsenka markerov disfunktsii pochechnogo transplantata u patsientov s sakharnym diabetom 1-go tipa posle transplantatsii pochki i sochetannoi transplantatsii pochki i podzheludochnoi zhelezy.

AIM: To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). SUBJECTS AND METHODS: The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-ß1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. RESULTS: The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=-0.36; p<0.05) and positively with the level of albuminuria (r=0.40; p<0.05). There was also a direct correlation of urinary podocin concentrations with blood creatinine levels (r=0.35; p<0.05) and that of NGAL with albuminuria (r=0.35; p<0.05) in recipients after transplantation. CONCLUSION: The high levels of biomarkers for kidney graft dysfunction in the examinees (including subjects after SPKT) reflect the persistence of graft microstructural injuries in clinically stable function.