[Autoimmune polyendocrine syndrome in adults. Focus on rheumatological aspects of the problem: A review].

Autoimmune polyglandular syndromes (APS) are a heterogeneous group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of central or peripheral immune tolerance. These syndromes are also often accompanied by autoimmune damage to non-endocrine organs. Taking into account the wide range of components and variants of the disease, APS is usually divided into a rare juvenile type (APS 1) and a more common adult type (APS 2-4). APS type 1 is caused by a monogenic mutation, while APS types 2-4 have a polygenic mode of inheritance. One subtype of adult APS (APS 3D) is characterized by a combination of autoimmune thyroid disease and autoimmune rheumatic disease. This review considers the available literature data on combinations that meet the above criteria. Many studies have noted a significantly higher prevalence of rheumatic diseases in patients with autoimmune thyroid disease compared with the control group. Also, as in a number of rheumatic diseases, a more frequent occurrence of autoimmune thyroiditis, primary hypothyroidism and Graves' disease was noted.

[Adrenocortical cancer: late diagnosis of the disease on the example of a clinical case. Case report].

Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li-Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.

[Assessing of iodine consumption with iodized salt in organized nutrition of children of preschool and school age in the Tyumen region].

The territory of the Tyumen region is an endemic region with insufficient iodine content in the environment, in which, since the early 1990s, active preventive measures have been taken to increase the use of iodized salt (IS) in households, catering and the food industry. The purpose of the research was to assess the consumption of iodine with IS used in the organized nutrition of children in the Tyumen region. Material and methods. The assessment of iodine intake was carried out in preschool institutions and schools randomly selected the city of Tyumen and rural areas (village of Isetskoye). Modeling of iodine consumption in organized groups was carried out for children aged 1-3, 3-7, 7-11 and 12 years and older in urban and rural areas, respectively, using a standard menu and a technological map of dishes. Iodine intake was estimated based on the content of 40 µg of iodine in 1 g of salt and its 30% loss during cooking. Model 1 assumed the mandatory use of IS in the preparation of all salt-containing meals for preschoolers and schoolchildren. Model 2, in addition to the mandatory use of IS in school and preschool meals accounted the consumption of iodine with bakery products (BP) produced with IS. Results. The modeling showed that the average intake of iodine with meals (model 1) in preschool institutions in Tyumen was 89±16 µg/day for children aged 1-3 years. When BP with IS were included in the menu (model 2), iodine intake increased to 101±14 µg/day. In children aged 4-7 years iodine intake was 115±18 and 126±18 µg/day, respectively. In rural areas, iodine intake was lower: in children aged 1-3 years, under model 1, iodine intake was 66±3 µg/day, under model 2 - 76±4 µg/day. In children aged 4-7 years, these figures were 83±3 and 92±4 µg/day, respectively. Iodine consumption in a school in Tyumen under model 1 in children 7-11 years old was 24±5 µg/day, and in children 12 years and older - 27±6 µg/day. When BP with IS were included in the menu (model 2), iodine intake increased to 32±5 µg/day in children 7-11 years old and to 39±6 µg/day in children 12 years of age and older. In rural areas, when using model 1, iodine intake in children aged 7-11 years was 37±15 µg/day, in children aged 12 and over 40±21 µg/day. When BP with IS were included in the menu (model 2), iodine intake increased to 44±15 µg/day in children aged 7-11 years and to 50±21 µg/day in children 12 years of age and older. Conclusion. The use of IS in the preparation of salt-containing meals in preschool educational institutions of the Tyumen region fully covered the iodine requirements of preschool children, which confirms the effectiveness of the chosen strategy for the prevention of iodine deficiency and can be considered as an important part of the concept of universal salt iodization. The use of IS in preparation of school breakfast meals provides 23.5-36.9% of the recommended nutrient intake for iodine in rural schools and 15.4-26.4% of the recommended nutrient intake in urban schools, which can be a significant contribution to the total intake of this micronutrient.

[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.

[Intermittent fasting: endocrine aspects: A review].

The increasing number of overweight and obese people makes the search for new effective ways to reduce body weight extremely urgent. Recently, intermittent fasting has received a lot of attention, as a dietary protocol, presumably effective in reducing body weight. Despite the large number of studies, the effects of intermittent fasting on the human body are controversial, since studies differ in dietary options, design, and often have a small sample size. In this review of the literature, the authors cite the results of studies of the effectiveness of intermittent fasting in patients with obesity, diabetes mellitus, and high risks of developing cardiovascular diseases.

[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

[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.

[Chromogranin A in diagnosis of pheochromocytoma (comparative analysis)].

AIM: To study the prognostic value of determining Chromogranin A blood level in the diagnosis of PHEO. MATERIALS AND METHODS: We conducted a comparative analytical study of 157 patients with suspected PHEO, statistical analysis of 24-hour urinary metanephrine and normetanephrine excretion test was performed, as well as a blood test for CrA, in groups that included patients without PHEO, with primary tumor or its recurrence, confirmed according to MSCT and/or scintigraphy with MIBG and/or the clonidine suppression test. RESULTS: The parameters of efficiency of these methods were calculated by groups and it was noted that the lowest sensitivity of the CrA determination method was observed in the group with recurrence of PHEO (43.8%), their exclusion from the entire sample didnt change specificity of the method and it remained at a high level (85.45%), though sensitivity significantly increased up to 87.1%. Sensitivity of determining 24-hour urinary metanephrine excretion also increased significantly up to 96.8%, with 98.2% of specificity. The correlation between diameter of the tumor and its secretory activity was identified: small with CrA level (rho 0.491) and strong with total level of methylated catecholamines (rho 0.765). False positive results were more often observed in patients present with other neuroendocrine tumors (37.5%), as well as those taking proton-pump inhibitors (43.75%). The sensitivity and specificity of CrA determining method in the group of patients with methanephrins elevated within gray zone appeared to be 50 and 86.1%, respectively. CONCLUSION: A blood test for CrA can be recommended as a confirmatory test for diagnosing PHEO in cases of questionable methylated catecholamines indicators or in cases of suspected relapse of PHEO. The use of the test as a first-line method is only possible if there is no possibility to study methylated catecholamines. When interpreting CrA level, it is necessary to take into account the conditions that may cause false-positive results.

[The first Russian multicenter non-interventional registry study to study the incidence of vitamin D deficiency and insufficiency in Russian Federation].

AIM: To assess the incidence of vitamin D deficiency and insufficiency among the adult population living in the regions of the Russian Federation located at latitudes from 45 to 70. MATERIALS AND METHODS: Russian multicenter non-interventional registry study using the "cross-sectional" method. RESULTS: In this study, 72.1% of the examined have the status of vitamin D deficiency and insufficiency, while an adequate level was diagnosed in 27.8% of cases. When assessing the degree of vitamin D deficiency depending on the season, statistically significant differences (p0.00001) were found between the periods: vitamin D deficiency or insufficiency was observed in 84.2% of autumn and in 62.4% of spring. The highest incidence of vitamin D deficiency and insufficiency was recorded in males compared with females (p=0.013, 79 and 70.3% respectively). Vitamin D deficiency is observed in young people in the age subgroup of 1825 years (p0.001, 54% in the study as a whole) much more often than in older people Conclusion. The widespread high prevalence of vitamin D deficiency in the Russian Federation is not related to geographic region of residence, but to some extent depends on the season. The high-risk group for vitamin D deficiency and insufficiency is young men. The significant role of vitamin D in the human body justifies the need to supplement and clarify a single concept for the prevention, diagnosis and treatment of conditions associated with deficiency, so higher implementation of National Clinical Guidelines is needed.

[Iodine deficiency disorders as a non-infectious epidemic: a look at the problem at the tome of COVID-19 pandemic].

Radioactive iodine, flying out of the destroyed reactor of the Chernobyl nuclear power plant, like a corona virus quickly spread throughout Europe. Iodine deficiency in the regions of Ukraine, Belarus and Russia adjacent to nuclear power plants became a factor in increased uptake of radioactive iodine by the thyroid gland in children and after 5 years led to an epidemic of thyroid cancer. Optimal iodine intake could become a kind of vaccination, which sharply reduces the risk of developing thyroid cancer, as has happened after the accident at the Fukushima nuclear power plant in Japan. Endemic goiter was eliminated 50 years ago, but returned to the country in the early 1990s after the collapse of iodized salt production and has not been eliminated to this day due to the lack of a legislative framework for mandatory salt iodization. The actual average consumption of iodine by residents of Russia is from 40 to 80 mcg per day, which is 23 times less than the recommended norm. Mild and moderate iodine deficiency was detected throughout the Russian Federation, and it is more typical for the the rural population. The iodine deficiency has the greatest negative effect on the psychomotor development of the child during the critical period the first 1000 days of life from the moment of conception to the end of the second year of life. According to WHO, over the past 20 years, iodine deficiency has been eliminated in 115 countries of the world, and the number of iodine-deficient countries has dropped to 25, but Russia is still among them. We believe that after the COVID-19 pandemic, it will no longer be necessary to prove the need for effective support for the prevention of both infectious and non-infectious diseases, and the declared preventive direction of Russian medicine will indeed become such.

[The prevalence of newly diagnosed autoimmune diseases among patients with Graves' disease and autoimmune polyglandular syndrome of adults].

Gravess disease is a common part of Autoimmune polyglandular syndrome (APS) and among thyroid autoimmune disorders is usually preceded the onset of the syndrome. AIM: The aim of this study was to determine the frequency of occurrence of APS type 2, 3 among patients with Graves disease. MATERIALS AND METHODS: Sera of 94 patients with Gravess disease, 116 patients with APS 24 types and 80 healthy subjects were screened for 21-OH Ab, insulin-Ab (IAA), Islet Cell-Ab (ICA), glutamic acid decarboxylase-Ab (GADA), protein tyrosine phosphatase-Ab (IA2), Zinc Transporter 8-Ab (ZnT8), Anti-gliadin-Ab (IgA+IgG) (AGA), Anti-transglutaminase-Ab (IgA+IgG) (Anti-tTG), Anti-parietal cell-Ab (APCA), Intrinsic Factor-Ab (IF), Rheumatoid factor (RF), Anti Ovarian Antibodies (AOA). Serum cortisol, fasting plasma glucose levels were measured. RESULTS: The presence of Addisons disease and the onset of Type 1 DM was not determined among Graves disease patients. None of the patients with Graves disease and in the healthy control group had 21-OH-antibodies detected. The frequency of 21-OH-Ab was 4.2% in APS type 3 (p=0.07) and 91.6% in APS type 2, 4 (p0.001). The prevalence of diabetes-associated autoantibodies was 20.2% among Gravess disease patients against 8.75% in healthy subjects control group (p0.05); OR 2.64; 95% CI 1.056.66 and 30.2% in APS of adults (DM 1 negative group) (p=0.18). The prevalence of APCA-markers of autoimmune gastritis was 31.9% in Gravess disease, 48.3% in APS 24 types (p=0.01); OR 1.99; 95% CI 1.183.51, and 12.5% in control group (p0.01); OR 3.28; 95% CI 1.497.24. There were no significant differences in the frequency of occurrence of IF-Ab and RF-Ab in the groups. The frequency of AGA and ATA was 28.7% in Graves disease, 36.2% in APS types 24 (p=0.3), 10% in the control group ((р0.01); OR 3.63; 95% CI 1.548.54. Graves disease patients with risk of developing APS type 3 (positive diabetes-associated and other autoantibodies) had relatives with autoimmune diseases in 57.5% of cases (p=0.05); OR 2.18; 95% CI 1.034.63. CONCLUSION: Graves disease patients are at high risk for future development of APS 3 type, especially those with inheritance for autoimmune diseases. Screening for the immunological markers, pathognomonic for coexisting autoimmune diseases in such patients with Graves disease, as well as in patients with APS type 3, should be done regularly.

[The prevalence of autoimmune endocrine diseases in vitiligo patients].

Vitiligo is a common polygenic autoimmune disease in which the foci of depigmentation are formed on the skin and/or mucous membranes as a result of the death of melanocytes. There are several hypotheses for the pathogenesis of the disease, the leading role among them is played the autoimmune hypothesis. This review summarizes the available literature data on the prevalence and structure of comorbid endocrine autoimmune pathology in vitiligo patients. In most studies conducted in Europe, America and Asia the prevalence of autoimmune thyroid diseases (including autoimmune thyroiditis and Graves disease), diabetes mellitus and autoimmune adrenal insufficiency was higher in vitiligo patients than in the general population. The results of some studies indicate a frequent association of vitiligo with autoimmune polyglandular syndromes. In the structure of comorbid pathology the highest prevalence was in autoimmune thyroid diseases. A number of studies have established a higher prevalence of autoimmune endocrine diseases in women, as well as in nonsegmental vitiligo patients and in cases of family history of vitiligo and/or other autoimmune diseases. In addition, it was shown that the prevalence of endocrine diseases increases with increasing area of depigmentation. The data obtained justify the advisability of conducting a timely examination of vitiligo patients with the aim of early detection of comorbid diseases and the appointment of appropriate treatment. Further studies are needed to investigate the effect of the identified associations on the course of vitiligo and comorbid endocrinopathies, as well as the effectiveness of therapy and the quality of life of patients.

[Primary hyperaldosteronism: difficulties in diagnosis].

Primary hyperaldosteronism (PA) - is the clinical syndrome, results from autonomous of the major regulators of secretion, aldosterone overproduction by a tumorous or hyperplastic tissue in adrenal cortex. Being the most frequent cause of secondary hypertension, PA may be represented by disorders with unilateral or bilateral aldosterone overproduction and differential diagnosis between them is crucial for choosing a right therapeutic approache: lifelong medical therapy with mineralocorticoid receptor antagonists or unilateral adrenalectomy. Adrenal venous sampling (AVS) is currently the «gold standard¼ test for identifying laterality of excess hormone production, unlike imaging tests, sensitivity and specificity of which is not enough, due to inability to evaluate functional activity with confidence, and also to limitations in detecting tiny abnormalities of adrenals, such as microadenoma or hyperplasia. Excluding certain cases, AVS is recommended to patients with confirmed PA, planning surgical treatment, to determine the lateralization of aldosterone hypersecretion. Described clinical case of patient with confirmed lateralization from adrenal without any detected lesions on CT-imaging and nonfunctioning tumour on contralateral side, highlights the importance of using AVS for decision to refer patients for surgery.

The association between the development of autoimmune polyglandular syndrome in adults and polymorphism of HLA class II genes and the predisposition to the development of chronic adrenal insufficiency in the context of these syndromes.

AIM: To consider association of chronic adrenal insufficiency in patients with APS of adults with polymorphism of class II HLA genes, -CTLA-4 and PTPN-22. MATERIALS AND METHODS: The case-control study involved 78 patients with APS 2, 3, 4 types and 109 healthy subjects). Alleles of the HLA class II genes, CTLA-4 and PTPN-22 were identified by the multiprimer allele-specific PCR method. The statistical analysis was carried out using the exact two-sided Fisher test. The association of the chronic adrenal insufficiency in patients with APS was determined by the value of the odds ratio (OR - odd's ratio), the value of 95% confidence interval (95% CI - confidence interval). RESULTS: Haplotypes DR3-DQ2 (OR = 4.06), DR4-DQ8 (OR = 5.78), genotype DR3/DR4 (OR = 19.7), DQA1 * 0301 allele (OR = 4.27), as well as genotype DQA1 * 0301 / DQA1 * 0501 (OR = 13.89) predispose to the development of APS of adults compared to the control group. APS patients were divided into two groups according to the presence of chronic adrenal insufficiency (APS 2 and 4 types - in one group and type 3 APS in the other group). Haplotype DR3-DQ2 (DRB1 * 17-DQA1 * 0501 -DQB1 * 0201) (OR = 2.6), as well as the genotype DR3/DR4 (OR = 4.28) found the strongest association with the development of adrenal insufficiency in patients with APS of adults. Protective haplotypes DRB1 * 01-DQA1 * 0101-DQB1 * 0501 (p<0.01, OR = 0.07), as well as the DRB1 * 01 allele (p<0.01, OR = 0.08) have been identified with respect to the development of adrenal insufficiency in adult APS patients. CONCLUSION: Examination of patients with APS of adults without chronic adrenal insufficiency for the presence of protective genes for the development of adrenal insufficiency will allow better predicting the risks of developing of the disease within the syndrome.

[MiRNAs in the diagnosis of cardiovascular diseases associated with type 2 diabetes mellitus and obesity]. / MikroRNK v diagnostike serdechno-sosudistykh zabolevanii, assotsiirovannykh s sakharnym diabetom 2-go tipa i ozhireniem.

Worldwide, the number of patients with type 2 diabetes mellitus (T2DM), obesity, and cardiovascular diseases (CVD) continues to increase steadily. Despite long-term studies of obesity and concomitant diseases, the molecular genetic bases for the development of these pathological conditions have remained the subject of numerous investigations so far. Recent investigations point to the involvement of miRNAs as dynamic modifiers of the pathogenesis of various pathological conditions, including obesity, T2DM, and CVD. MicroRNAs are involved in various biological processes underlying the development of CVDs, including endothelial dysfunction, cell adhesion, and atherosclerotic plaque formation and rupture. Some of them are considered as potential sensitive diagnostic markers of coronary heart disease and acute myocardial infarction. Approximately 1,000 microRNAs are found in the human body. It has been determined that miRNAs regulate 30% of all human genes. Among them there are about 50 circulating miRNAs presumably associated with cardiovascular diseases. This review provides recent data on the participation of some miRNAs in various pathological and physiological states associated with CVD in DM and obesity. An extended and exact understanding of the function of miRNAs in the gene regulatory networks associated with cardiovascular risk in obesity will be able to reveal new mechanisms for the progression of disease, to predict its development, and to elaborate innovative therapeutic strategies.

[Incretin secretion and glucose metabolism in morbidly obese patients in the early and late periods after biliopancreatic diversion]. / Produktsiya inkretinov i obmen glyukozy u bol'nykh patologicheskim ozhireniem v rannem i otdalennom periode posle biliopankreaticheskogo shuntirovaniya.

AIM: To estimate the parameters of glucose metabolism and to assess the secretion of incretins in patients after biliopancreatic diversion (BPD) for morbid obesity (MO) in the early and late postoperative periods. SUBJECTS AND METHODS: The prospective part of the investigation included 22 patients with a body mass index of 35.8 to 68.4 kg/m2 and type 2 diabetes mellitus (T2DM). All the patients were examined before, 3 weeks and 3 months after BPD. The retrospective part covered 23 patients who were examined after BPD for MO; the postoperative period was 4.7 [2.3; 7.2] years. A control group consisted of 22 healthy, normal weight volunteers. A 75-g oral glucose tolerance test was carried out in all the groups to study the levels of glucose, immunoreactive insulin (IRI), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon at 0, 30, 60, and 120 min. RESULTS: T2DM patients showed improvement in glucose metabolism just 3 weeks after BPD; following 3 months, they had normalized fasting blood glucose levels (5.6 [5.0; 6.0] mmol/l). During 3 months, glycated hemoglobin decreased from 7.5 [6.6; 8.5] to 5.7 [5.3; 5.9]%. In the early period following BPD, there was an increase in basal and postprandial GLP-1 levels associated with the peak IRI concentration. In the late period after BPD, the enhanced secretion of IRI and GLP-1 persisted, which was followed by a reduction in postprandial glucose levels in 4 of the 23 patients. CONCLUSION: T2DM remission does not depend on weight loss in the early period after BPD. In this period, the significant improvement of glucose metabolic parameters in patients with obesity and T2DM is associated with elevated GLP-1 levels. The altered incretin response is a stable effect of BPD and remains in its late period.

[Adrenocortical oncocytoma].

The paper characterizes adrenocortical oncocytoma, a rare adrenal tumor, accompanied by Cushing's syndrome and estrogen and androgen production and provides histological and immunohistochemical features. The authors describe their observation of a 33-year-old female woman. It is shown that estimation of the malignant potential of adrenocortical oncocytomas requires a special approach and must be done using the Lin-Weiss-Bisceglia criteria.

[Hereditary pheochromocytoma-associated syndromes. Part 1].

Pheochromocytoma (PCC)/paraganglioma is a catecholamine-secreting tumor of the paraganglion. The hereditary variants of PCC have been previously considered to occur in 10% of cases. The latest researches have clearly demonstrated that the hereditary cause of chromaffin tumors is revealed in a much larger number of patients. There have been the most investigated NF, RET, VHL, SDHD, SDHC, and SDHB gene mutations. New EGLN1/PHD2, KIF1B, SDH5/SDHAF2, IDH1, TMEM127, SDHA, MAX, and HIF2A gene mutations have been recently discovered. This review describes new ideas of the genetic bases of PCC. The authors discuss criteria for patient referral for genetic examination on the basis of the phenotypic.manifestations of mutations, such as a malignant course, bilateral adrenal lesion, and age at disease manifestations. Recommendations are determined for carriers to screen for the components of hereditary pathology.

[Hereditary pheochromocytoma-associated syndromes. Part 2]. / Nasledstvennye sindromy assotsiirovannye s feokhromotsitomoi. Chast' 2.

Pheochromocytoma (PCC)/paraganglioma is a catecholamine-secreting tumor of the paraganglion. The hereditary variants of PCC have been previously considered to occur in 10% of cases. The latest researches have clearly demonstrated that the hereditary cause of chromaffin tumors is revealed in a much larger number of patients. There have been the most investigated NF, RET, VHL, SDHD, SDHC, and SDHB gene mutations. New EGLN1/PHD2, KIF1В, SDH5/SDHAF2, IDH1, TMEM127, SDHA, MAX, and HIF2А gene mutations have been recently discovered. This review describes the most common PCC-associated syndromes in detail and considers the specific features of new mutations.

[SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME].

Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.