BACKGROUND. The feasibility of using molecular genetic markers for the diagnosis of thyroid tumors and the impact on the prognosis of thyroid cancer are being actively investigated. The most interesting are genes, the detection of which is associated not only with thyroid cancer, but also with a more aggressive course of the disease. The ability to diagnose the molecular profile of minimally invasive methods with the study of freely circulating DNA tumor tissue in blood plasma is a modern trend of medicine.

AIMS: to evaluate the frequency of somatic mutations in the «hot spots» of BRAF, KRAS, KRAS, EIF1AX and TERT genes in circulating DNA of blood plasma.

MATERIALS AND METHODS. Samples of DNA, extracted from the removed tumor and non-tumor thyroid tissue, were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX and then in identifying mutations and testing appropriate samples of free circulating DNA in blood plasma.

RESULTS. mutations in the» hot spots «of the BRAF gene (exon 15, codon area 600-601) were found in 54 patients, mutations in the» hot spots « of the NRAS gene (exon 3, codon 61) – in 12 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. In freely circulating blood plasma DNA, BRAF gene mutations were detected in 1 case, NRAS gene mutations were detected in 1 case.

CONCLUSIONS. the use of freely circulating DNA of blood plasma in the testing of the studied sample did not show the feasibility for the diagnosis of thyroid tumors.

BACKGROUND. There is no unequivocal opinion regarding the safety of statin in patients with hypothyroidism. However, based on some new data, it can be assumed that hypothyroidism, even in a stage of compensation, may cause muscle damage in patients receiving statins. As part of this study, this hypothesis was tested, and was confirmed.

AIMS: To study the possibility of muscle damage and the nature of muscle metabolism in patients with compensated hypothyroidism who takes statin.

MATERIALS AND METHODS. The study is transverse and observational with the inclusion of 120 women, subdivided on three groups (n=40). The main group of patients with hypothyroidism who took statins (group 1) was compared with two control groups, including those who took statins without hypothyroidism (group 2), and who did not take statins with hypothyroidism (group 3).

RESULTS. Patients taking statins and have compensated hypothyroidism are more likely to develop complaints of muscle pain, which are often associated with the elevation of muscle lesion markers, as well as the presence of the C allele in the SLCO1B1*5 gene (c.521T>C). In patients with compensated hypothyroidism, relative frequency of occurance of muscle pain syndrome associated with CPK elevation increases with TSH levels above 2.86 mU/L. Compensated hypothyroidism increases the possibility of development of SPM-ATP by 2.7 times.

CONCLUSIONS. Compensated hypothyroidism is not a contraindication for statin therapy. However, the presence of even compensated hypothyroidism in patients taking statins increases the possibility of the development of muscle symptoms associated with taking statins, and requires additional monitoring of the clinical and biochemical parameters of muscle metabolism (especially the level of CPK).

BACKGROUND. The problem of differential diagnosis of constitutional delay of puberty/CDP and hypogonadotropic hypogonadism/HH in boys is discussed, as boys have similar genetic mechanisms and appearance.

AIMS: to determine accuracy of the criteria for the differential diagnosis of CDP and HH.

MATERIALS. The study included 56 boys 14.4±0.7 years old with delayed puberty (G1P1-3/testicular volume <3 сm³). We excluded patients with hypergonadotropic hypogonadism, treated with sex steroids or gonadotropins for 12 months, with endocrine/somatic diseases affecting puberty. At the first visit, we evaluated anthropometric data, bone age, testicular volume, hormones and the results of the gonadotropin-releasing hormone test (GnRH) agonist test and the human chorionic gonadotropin test (hCG) test. The HH was defined by a testicular volume <3 сm³ after 2 years follow-up. The patients were divided into two groups: the first group with CDP and testicles ≥3 cm³ (n=50) and the second group with HH and testicles <3 cm³ (n=6).

RESULTS. At the first visit in boys with CDP corrected target height was less (Me SDS –1.8 vs –0,4, р=0.02), bone age was less (Ме SDS –2.5 vs –0.2 р=0.03), testicular volume was more (Ме 1.9 vs 0.5, p=0.0003), hormones were significantly higher, such as LH (Ме 1.1 vs 0.1 mIU/ml, p=0.0002), FSH (Ме 1.9 vs 0.2 IU/l, p=0.00007), inhibin B (Ме 142.3 vs 31.3 pg/ml, p=0.00009), max LH (Ме 18.9 vs 0.6 mIU/ml, p=0.00007), max LH/FSH (Ме 2.3 vs 0.4, p=0.0002) on the GnRH agonist test and Δ testosterone (Ме 14.4 vs 1.1 nmol/l, p=0.0001) on the hCG test than in boys with HH. The LH ≥0.3 mIU/ml had 86% sensitivity, 100% specificity; max LH/FSH ≥1 – 92% sensitivity, 100% specificity; Δ testosterone ≥2.7 nmol/l on the hCG test – 98% sensitivity, 100% specificity for differential diagnosis of CDP and HH in boys. However, max LH ≥3.5 mIU/ml on the GnRH agonist test, FSH ≥0.5 IU/l, inhibin B ≥58 pg/ml had 100% sensitivity and specificity for diagnosis of CDP.

CONCLUSIONS. The inhibin B ≥58 pg/ml, LH ≥0.3 mIU/ml, FSH ≥0.5 IU/l or max LH ≥3.5 mIU/ml, max LH/FSH ≥1,0 on the GnRH agonist test, Δ testosterone ≥2.7 nmol/l on the hCG test have an excellent accuracy for the differential diagnosis of CDP and HH in prepubertal boys with delayed puberty.

BACKGROUND. The prevalence of essential hypertension (ЕH) is increasing every year, both in Russia and around the world. Genetic and environmental risk factors are involved in the development of hypertension, and obesity plays an important role. Therefore, the study of gene-ecological interactions in the development of hypertension seems to be relevant.

AIMS: to study the gene-environment interactions between polymorphic loci of MMP and obesity in essential hypertension in women.

MATERIALS AND METHODS. The study was conducted in a case-control design. The sample included 584 subjects: 375 patients with EH and 209 women in the control group. All individuals included in the study were genotyped for eight polymorphic loci of MMPs. The study of the gene-environmental interactions during the formation of hypertension was performed using the GMDR method (Generalized Multifactor Dimensionality Reduction, http://www.ssg.uab.edu/gmdr).

RESULTS. rs11568818 MMР7 and rs11225395 MMР8 polymorphic loci were found to be involved in the development of arterial hypertension in women without obesity (p<0.050). Fifteen three-, four-, and five-factor models of gene-environmental interactions of 8 MMPs with obesity, associated with EH (p=0.01), were found. It is shown that the analyzed SNPs are located in the DNA regions that bind to histones, marking promoters and enhancers, in the region of hypersensitivity to DNAse-1, in the binding sites of regulatory proteins and transcription factors. The loci of MMPs rs17577, rs11568818, rs1320632 and rs11225395 have cis-eQTL-value. They affecting the expression of the genes of MMP7, SNX21, SLC12A5 and RP11-817J15.3.

CONCLUSIONS. SNP rs11568818 MMP7 and rs11225395 MMP8 and gene-environmental interactions of MMPs rs1799750, rs243865, rs3025058, rs11568818, rs1320632, rs11225395, rs17577, rs652438 with obesity are involved in the development of essential hypertension in women.

Background: Monitoring glycemic control in diabetes includes daily measurements of glucose levels at home, along with periodic monitoring of glycemia indicators on the whole. The main purpose of monitoring glycemic control is to accurately and authentically assess the glycemic level reached by each patient in order to ensure the glycemic goals achievement. Glycemic control assessment at a certain point in time is best achieved by self-monitoring the level of glucose in the blood, in that allows you to assess the presence of hyperglycemia and hypoglycemia to optimize the treatment strategy.

Aims: Accuracy assessment of a medical device «Portable blood glucose concentration meter with electrochemical single-use strip PKG-03 «Satellite Express» for glycemic control of children with diabetes.

Materials and methods: In a group of children with diabetes (n=105, age from 1 month to 17 years), simultaneously was taken capillary blood from one drop to assess the accuracy of glycemia levels on the «Satellite Express» glucose meter and on the laboratory glucose and lactate analyzer SUPER GL.

Results: In a comparative analysis of 660 blood samples on the Clark error scale, was found that all deviations of glycemia values obtained with the «Satellite Express» glucose meter were in zones A (99.7% — clinically correct values) and B (0.3% — safe deviations). The limits of permissible systematic error of measurements that meet the requirements of the National Standard of Russian Federation GOST R ISO 15197-2015 in terms of clause 6.3 System Accuracy amounted to 96.8% of deviations of glucose meter indications from reference values, which matches to areas of clinically correct and safe deviations.

Conclusion: Using the «Satellite Express» glucose meter in clinical practice makes it possible to control glycemia qualitatively and it is safe for children aged from 1 month to 17 years.

Due to the high prevalence of low vitamin D levels in the overwhelming majority of regions of the world and discovery of extra-skeletal effects of vitamin D, the issue of maintaining adequate levels of vitamin D in the blood remains extremely relevant, especially in people with high risk of severe deficiency. To date, few studies have been performed on the features of vitamin D metabolism in disorders such as hypercorticism and acromegaly. However, vitamin D deficiency in such patients, according to available literature, may be more widespread and more pronounced than in general population. It is now recommended to use standard prophylactic and therapeutic doses of vitamin D for the treatment of these diseases, which may not satisfy the therapeutic goals specific to each disease. This review provides information on normal vitamin D metabolism, as well as literature data on the possible relationship and mutual influence between these endocrinopathies and vitamin D metabolism.

A large number of socially significant diseases is accompanied with oxidative stress and carry with tissue damage. Free radicals play a crucial role in the development of these diseases. Similar processes occur under the influence of ionizing radiation and bacterial infections. Recently, was indicated the significant role of oxidative stress in the development of autoimmune thyroiditis. It is assumed that the synthesis of thyroid hormones depends on the concentration of H₂O₂, which, due to its high toxicity, must be in strict accordance with the activity of antioxidant systems. Many biochemically negative processes occur on the apical membrane of the thyrocyte, which allows limiting the effect of free radicals and avoid cell destruction. However, in pathological conditions, enzymatic systems are disturbed and their components become abnormally activated in the cytoplasm, and it is leads to functional and morphological disorders. A deeper understanding of oxidative stress and its role in the development of autoimmune thyroiditis can contribute to the identification of new methods for its assessment, the expansion of therapeutic ranges for this disease. This review discusses oxidative stress, which is the accumulation of active damaging agents (free radicals, prooxidants, reactive oxygen species) that initiate cell damage and lead to the development of various pathological conditions.

The specific relationship between the endocrine and immune systems is represented by a numerous number of factors and mechanisms that form the structure and ensure the function of each of the two systems. For example, immunocompetent cells can produce immunologically active substances, as well as some hormones. On the other hand, immune cells are available to the effects of endogenous hormones. Currently, the so-called cross-regulation of endocrine and immune mechanisms in an equilibrium of pro-and anti-inflammatory responses has not been sufficiently studied. Among other autoimmune lesions, autoimmune thyreopathy occupies a significant place. The development of an autoimmune lesion of the thyroid gland is a complex process, which is the result of the interaction of infiltrating lymphocyte and thyrocyte tissue that can express a wide range of molecules involved in the immune response. Immunological and immunogenetic factors play a major role in the pathogenesis of autoimmune thyroid diseases, such as autoimmune thyroiditis and Graves disease. Despite the fact that more than 100 years have passed since the first description of autoimmune thyroiditis and Graves disease has been known for many centuries, the mechanisms of these pathologies are still not fully understood.

Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of antibodies to 21-hydroxylase is a method that helps establish the etiology of the disease – the autoimmune genesis of adrenal gland damage. On the other hand, the determination of autoantibodies to 21-hydroxylase is the only prognostic factor of the risk of adrenal insufficiency, which makes it possible to prevent the development of acute adrenal crisis. The article provides a brief literature review on autoantibodies to 21-hydroxylase and the pathogenesis of autoimmune adrenal insufficiency, and a series of clinical cases that illustrates the significant role of autoantibodies to 21-hydroxylase in diagnosis of adrenal insufficiency.

One of the reasons for the development of hypoglycemia is the synthesis of autoimmune antibodies to insulin or its receptor – insulin autoimmune syndrome (IAS). The largest number of cases of this syndrome is described in the Japanese population. The antibodies to insulin are most often polyclonal immunoglobulins. In monoclonal gammopathy of undetermined significance and multiple myeloma secreted pathological monoclonal immunoglobulin may have an affinity for human insulin, which induces the development of IAS. The prolonged persistence of episodes of hypoglycemia of unknown origin requires the exclusion of the monoclonal nature of secreted antibodies to insulin. Often the presence of pathological secretion for a long time is not recognized due to the absence of other manifestations of the disease. The manifestation of gammopathy is represented by a wide range of symptoms and syndromes requiring the collaboration of doctors of various specialties. This review summarizes the literature on IAS in patients with monoclonal gammopathy, whose disease debuted from episodes of spontaneous hypoglycemia. When hemoblastosis remission is achieved (when the secretion of the pathological protein is minimal or not determined), the glucose, insulin, and antibodies levels of insulin normalize, and when multiple myeloma recurs, episodes of hypoglycemia resume. The onset of the disease from the IAS can be considered as a new criterion for symptomatic multiple myeloma, dictating the need for the initiation of specific therapy.