[Comparative analysis of bone complications/manifestations in sporadic and MEN1-related primary hyperparathyroidism].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) - is a rare syndrome with an autosomal dominant inheritance pattern caused by a mutation in the tumor suppressor gene (MEN1). Parathyroid involvement is the most common MEN1 manifestation resulting in primary hyperparathyroidism (mPHPT). Data on the prevalence and structure of bone disease in mPHPT compared to sporadic one (sPHPT) are often incomplete and contradictory. AIM: The purpose of this study was to compare the severity of bone involvement between mPHPT and sPHPT. MATERIALS AND METHODS: A single-center retrospective study was conducted among young patients in the active phase of PHPT and without prior parathyroidectomy in anamnesis. The analysis included the main parameters of calcium-phosphorus metabolism, bone remodeling markers, as well as an assessment of disease complications. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at sites of lumbar spine, femur and radius. Trabecular bone score (TBS) was applied to estimate trabecular microarchitecture. All patients included in the study underwent genetic testing. RESULTS: Group 1 (mPHPT) included 26 patients, and group 2 (sSHPT) included 30 age-matched patients: the median age in group 1 was 34.5 years [25; 39], in group 2 - 30.5 years [28; 36], (p=0.439, U-test). Within group 1, the subgroup 1A (n=21) was formed with patients without other hormone-produced neuroendocrine neoplasms (NEN) in the gastrointestinal tract (GI) and the anterior pituitary gland. The duration of PHPT was comparable in both groups: mPHPT - 1 year [0; 3] versus sPHPT - 1 year [0; 1], (p=0.533, U-test). There were no differences in the main parameters of calcium-phosphorus metabolism, as well as in the prevalence of kidney complications. In the mPHPT group, bone abnormalities were observed significantly more often compared to sPHPT: 54 vs 10% (p=<0.001; F-test). Statistically significant differences were revealed both in BMD and in Z-score values of the femoral neck and total hip, which were lower in the mPHPT group. These differences remained significant when comparing subgroup 1A with sPHPT. CONCLUSION: MEN1-associated PHPT may be accompanied by a more severe decrease in BMD in the femoral neck and total hip compared to sPHPT regardless of the other hormone-producing NEN. Clarifying the role of mutation in the MEN1 gene in these processes requires further study.

[Hyperparathyroidism of different genesis in young patients with Turner syndrome: case series and brief review].

Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient's normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.

[Predicting the presence of MEN1 gene mutation based on the clinical phenotype of patients with primary hyperparathyroidism].

BACKGROUND: Timely referral of patients for genetic testing to rule out MEN1-associated primary PHPT is important factor in determining treatment strategy and prognosis. In the context of the limited availability of genetic testing, the search for clinical markers indicative of MEN1 gene mutations remains an extremely relevant task. AIM: To determine the diagnostic value of clinical features of primary PHPT in young patients for predicting the presence of MEN1 gene mutations. MATERIALS AND METHODS: A single-center, prospective study was conducted at the Endocrinology Research Centre, involving 273 patients with PHPT in the period 2015-2022. Based on the results of genetic and laboratory tests, patients were divided into three groups: those with MEN1 gene mutations (MEN+ group, n=71), those without MEN1 gene mutations - isolated sporadic PHPT (MEN- group, n=158), and patients with PHPT and associated endocrine gland disorders - MEN-1 syndrome phenocopies (PHEN group, n=32). Subgroups of patients younger than 40 years of age were also identified. Comparative analysis was performed among the independent groups and subgroups, and logistic regression analysis was used to develop a mathematical model for predicting the probability of the presence of MEN1 gene mutation. RESULTS: Patients in the MEN+ and MEN- groups were comparable by gender and age at manifestation, as well as calcium-phosphorus metabolism parameters and PHPT complications. In the PHEN group, PHPT manifested at older age compared to the other groups (p<0.001 for all), with lower total calcium levels and a trend toward lower iPTH concentrations. The MEN+ group had a significantly higher frequency of multiglandular parathyroid (PG) involvement, PHPT recurrence, and positive family history compared to the MEN- and PHEN groups. Histologically, adenomas predominated in the PHEN and MEN- groups (92% and 94%, respectively), whereas hyperplasia of PGs were more common in the MEN+ group (49%). None of the PHEN patients had all three «classic¼ components of the MEN-1 syndrome, and the clinical course of PHPT was similar to that of the MEN- group. These differences were also observed in the subgroups of patients younger than 40 years, which formed the basis for the development of a mathematical model. The logistic regression equation for predicting the probability of the presence of the MEN1 gene mutation included eight predictors, with a diagnostic sensitivity of 96% and specificity of 98%. CONCLUSION: Based on the analysis performed, eight hereditary predictors of PHPT within the MEN-1 syndrome were identified. A mathematical model was developed to predict the presence of the MEN1 gene mutation in patients, which demonstrated high classification performance on the training dataset. Further refinement of the model will help improve the quality of medical care for patients with PHPT.

[Experience in using teriparatide for the treatment of postoperative hypoparathyroidism in hemodialysis patients].

The frequency of chronic postoperative hypoparathyroidism after total parathyroidectomy for secondary and tertiary hyperparathyroidism in patients with end-stage renal failure, according to various authors, can reach 20% or more. Prescribing active metabolites of vitamin D and calcium it is not always sufficient for achievement of target goals. This dictates the need for replacement therapy with recombinant parathyroid hormone. Teriparatide is the only drug of this series approved by the American Food and Drug Administration (FDA) and registered in the Russian Federation. However, it is registered as an anabolic anti-osteoporotic drug and is not indicated for the treatment of chronic hypoparathyroidism. The use of teriparatide in postoperative hypoparathyroidism in patients receiving renal replacement therapy with programmed hemodialysis in the Russian Federation has not been previously studied. Data on this issue is also limited in foreign literature. However, it is a potential treatment option for hemodialysis patients with chronic hypoparathyroidism and severe bone disorders. In this article, we present 2 clinical cases of substitution and anabolic therapy with teriparatide in this cohort of patients.

[The short test with hydrochlorothiazide in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment].

BACKGROUND: Differential diagnosis between the normocalcemic primary hyperparathyroidism (nPHPT) and secondary hyperparathyroidism (SHPT) due to hypercalciuria remains a challenge. AIM: The aim of this study was to investigate the capability of short test with hydrochlorothiazide for the differential diagnosis of nPHPT and SHPT. MATERIALS AND METHODS: A retrospective study was conducted with the participation of 28 patients who underwent a functional test with thiazide diuretics during hospitalization in the Department of parathyroid glands pathology and mineral disorders of the Endocrinology Research Centre, Russia. Parameters of mineral metabolism were evaluated before and 3-5 days after taking hydrochlorothiazide 50 mg/day. RESULTS: According to baseline and dynamic biochemical evaluation patients were divided into 3 groups. Group 1 (n=21) included patients with confirmed PHPT, who reached hypercalcemia accompanying with an elevated level of iPTH (n=19) or an increased level of iPTH accompanying with normocalcemia (n=2). In group 1, baseline Caadj. was 2.48 mmol/l [2.47; 2.52], iPTH 107.5 pg/ml [86.8; 133.0], after short test - 2.63 mmol/l [2.59; 2.66] and 102.1 pg/ml [95,7; 124,1]. Group 2 included only one who was diagnosed with SHPT, a normal value of iPTH with concomitant normocalcemia was achieved after 4 days of hydrochlorothiazide therapy (baseline Caadj. 2.35 mmol/l, iPTH 74.5 pg/ml vs at 2.27 mmol/l and 50.7 pg/ml respectively). Patients with doubtful results of the test entered in group 3 (n=6), they did not achieve significant changes in the calcium and iPTH levels, so it was recommended to continue the test on an outpatient basis (baseline Caadj. 2.39 mmol/l [2.33;2.45], iPTH 97.0 pg/ml [83.1;117.0]); after short test - 2.47 mmol/l [2.42; 2.48] and 91.3 pg/ml [86.9; 124.0] respectively). Groups with PHPT and SHPT and doubtful results significantly differed from each other in Caadj (р=0.003, U-test, Bonferroni correction Р0=0.006), but not in iPTH, daily calciuria, eGFR, and phosphorus. There were no significant differences in the incidence of classical complications of PHPT. CONCLUSION: The diagnosis of PHPT was confirmed in 21/28 patients 3-5 days after taking hydrochlorothiazide 50 mg/day. The obtained results are significant for the differential diagnosis in hospitalized patients with an unspecified genesis of hyperparathyroidism.

Different treatment strategies in primary hyperparathyroidism during pregnancy.

PURPOSE: Primary hyperparathyroidism (PHPT) in pregnancy is rare enough and can be unrecognized because of nonspecific symptoms in most cases, but life-threatening complications for mother, fetus and neonate also occurs. PHPT requires frequent monitoring of the mother and fetus by a multidisciplinary team. Diagnostics and treatment approaches are limited and require individual risk-benefit assessment. METHODS: In this paper we describe 3 cases of PHPT in pregnant women with different managing approaches (surveillance, drug therapy and surgical treatment) and successful outcomes. Additionally, the most actual literature data on this problem is reviewed. RESULTS: The management of PHPT in pregnancy should be based on the clinical features, severity of hypercalcemia, gestational age and patient's preference. In the first case a conservative approach with low-calcium diet and oral hydration resulted in mother's reduced serum calcium level before delivery. The second patient had severe hypercalcemia and absolute indications for surgery that was successfully performed at 25 week of gestation. The third woman received cinacalcet because of severe hypercalcemia and potential perioperative risks in the third trimester with an improvement in well-being. CONCLUSION: Nowadays parathyroidectomy is the best choice for patients with symptomatic PHPT and severe hypercalcemia. This intervention should be carried out preferably in the second trimester to avoid maternal and fetal complications. Mild forms of the disease can require just a conservative management. The drug treatment of PHPT during pregnancy is still controversial.

[Clinical and demographic analysis of telemedicine «doctor-patient¼ consultations at the Endocrinology Research Centre].

BACKGROUND: The COVID-19 pandemic has accelerated the development of telemedicine technologies. Today there is evidence of the successful use of telemedicine in various fields of health care, in particular in endocrinology. At the same time, there is not enough information for effective integration of telemedicine into the management of patients with various endocrinopathies. AIM: The aim of this study is a clinical and demographic assessment of the structure of telemedicine consultations (TMC) conducted at the Endocrinology Research Centre in 2020-2021. MATERIALS AND METHODS: A single-stage, single-center retrospective study was conducted. The study included all patients who received at least one TMC at the Endocrinology Research Centre in 2020-2021. Clinical and demographic information was analyzed (gender, age of patients, region of residence, ICD-10 code). All patients signed voluntary informed consent for TMC. The obtained data were processed using the Microsoft Office 2013 software package. RESULTS: In 2020, 1,548 TMC were held, in 2021 - 4180 TMC. Among adults, women predominated in the structure of referrals (83-86%), among children there is a tendency towards equivalent referrals for boys and girls (in 2021 - 45% and 55%, respectively). The median age of adult patients in 2021 was 38 years [31; 53], among children - 11 years [7; 14]. In 2020, residents of 74 regions of the Russian Federation applied for TMC, in 2021 - of 82 regions. There is a tendency towards the prevalence of patients from the Central, Volga, Southern and North Caucasian federal districts in the TMC structure. Diseases of the thyroid gland predominated in the nosological structure of TMC. CONCLUSION: TMC turned out to be in demand in patients with a wide variety of endocrinopathies. It is important to conduct further analysis of both the TMC market and the effectiveness of remote counseling for various nosologies to determine the place of telemedicine in the modern healthcare structure and to introduce TMK into the system of clinical guidelines and programs of territorial compulsory medical insurance funds.

[Case of clinically "aggressive" course of primary hyperparathyroidism, algorithm of differential diagnosis].

Primary hyperparathyroidism (PHPT) is a significant endocrine disease caused by increased production of parathyroid hormone (PTH) by altered parathyroid glands and violation of the mechanisms of regulation of serum calcium concentrations. These changes can lead to nephrolithiasis, osteoporosis, erosive and ulcerative lesions of the gastrointestinal tract, a number of less specific symptoms (nausea, vomiting, weakness, fatigue, etc.). Etiologically, in more than 85% of cases, PHPT is a consequence of sporadic solitary adenoma or hyperplasia parathyroid glands, however, in 1-3% of cases, the cause is carcinoma of parathyroid glands , including as part of various genetic syndromes. The importance of timely examination for PHPT of patients with characteristic clinical manifestations of this disease and - with an aggressive course - alertness towards carcinomas of parathyroid glands was noted. At the same time, the severity of the clinical picture and even the presence of suspicious signs characteristic of hereditary forms of carcinomas of parathyroid glands are not always a consequence of the malignant process. We present a description of a young patient with a severe course of PHPT, multiple fractures and a voluminous tumor of the upper jaw, developed as a result of a typical adenoma of parathyroid glands. Additionally, the algorithm of pre- and postoperative differential diagnosis for such patients is highlighted.

[Assessment of the prevalence of anemia in patients with primary hyperparathyroidism: a single-center observational study].

BACKGROUND: The combination of primary hyperparathyroidism (PHPT) with anemia was first described in 1931. It remains unclear whether PHPT is the direct cause of anemia, or it develops due to PHPT's complications. The frequency of PHPT--associated anemia in the Russian population is unknown. AIM: To assess the prevalence of anemia in patients with PHPT admitted to the Department of Parathyroid Glands Pathology in the Endocrinology Research Centre from January 2017 to August 2020. MATERIALS AND METHODS: The study included patients with PHPT over 18 years old. A single-center observational one-stage one-sample uncontrolled study was carried out. We analyzed laboratory and instrumental data obtained during inpatient examination in accordance with the standards of medical care. Statistical analysis was performed using Statistica 13 (StatSoft, USA) and SPSS (IBM, USA) software packages. RESULTS: The study included 327 patients with PHPT, 28 (9%) men and 299 (91%) women. The median age was 59 years [51; 66]. 26 patients (8%) with anemia were identified. Statistically significant differences between patients with and without anemia were found only in the GFR. Comparison of patients with and without anemia didn't reveal any significant differences in the incidence of PHPT's complications.Significant differences in serum hemoglobin concentration and average hemoglobin concentration in erythrocytes were revealed between patients with and without vertebrae fractures. In the group of patients without compression fractures these parameters were higher.In the subgroup of patients with total calcium concentration above 3 mmol/L and PTH above 3 normal values, the incidence of anemia reached 21% (95% CI: 10%; 35%). Within this group we revealed tendencies to higher levels of PTH, ionized calcium and osteocalcin in patients with anemia. CONCLUSION: In general, there was no correlation between hypercalcemia, the degree of PTH elevation and the presence of anemia in patients with PHPT. However, in the subgroup of patients with severe hypercalcemia, there was a relationship between the concentration of PTH, ionized calcium and the presence of anemia. In patients with PHPT and vertebral fractures, significantly lower concentrations of blood hemoglobin and hemoglobin in erythrocytes were observed.

[Management of surgical complications following prolonged warfarin therapy in a general surgical hospital]. / Lechenie khirurgicheskikh oslozhnenii prolongirovannoi terapiei varfarinom v obshchekhirurgicheskom statsionare.

OBJECTIVE: To analyze an effectiveness of algorithm for complex treatment of patients with surgical complications of prolonged warfarin therapy in a general surgical hospital. MATERIAL AND METHODS: The study included 138 patients with surgical complications of prolonged warfarin therapy. All patients received warfarin for at least 6 months (49.5% of patients - over 5 years). Warfarin therapy was indicated for deep vein thrombosis in 54 patients and various cardiac diseases in 84 patients. Examination included clinical and instrumental survey, laboratory tests and coagulation tests - thromboelastography (TEG) and thrombodynamics test (TT). RESULTS: Recurrent VTEC occurred in 24 out of 138 patients, hemorrhagic complications - in 114 patients. Therapeutic management was applied in 111 patients, 27 ones underwent surgery (emergency treatment - 25 patients, after two days - 2 patients). Ten patients underwent endoscopic hemostasis, two patients - ultrasound-assisted percutaneous drainage of hematoma. Recurrent VTECs were caused by inadequate laboratory control and violations of warfarin therapy. Most of these patients underwent therapeutic management (only 3 patients required surgery for life-threatening flotation in great veins). Treatment of 114 patients with hemorrhagic complications of prolonged warfarin therapy depended on features of bleeding and severity of warfarin-induced coagulopathy. Depending on these factors, warfarin was discontinued and intravenous administration of vitamin K / FFP / prothrombin complex concentrate was applied. This approach ensured successful therapeutic measures in 90 patients of this group. Twenty-four patients underwent surgery after correction of hemostatic disorders. TT was characterized by high efficiency in analysis of thrombotic predisposition and prediction of the risk of VTEC. TEG was valuable for assessment of warfarin-induced coagulopathy and treatment of patients with hemorrhagic complications of prolonged warfarin therapy. CONCLUSION: The developed clinical and diagnostic algorithm for management of hemorrhagic complications of prolonged warfarin therapy ensures positive clinical results even in a general surgical hospital.

[NON-SURGICAL ASPECTS OF THYROID SURGERY].

The level of calcium in the blood serum, voice function, thyroid status and quality of life of patients up to 1 year after removal of the thyroid gland were studied. Thyroidectomy is an operation associated with a high risk of postoperative hypocalcemia with clinical manifestations (19.6%), which is transient in 15.5%, and permanent in 4.1%. After thyroidectomy transient voice disorders are observed that are not associated with paresis of the laryngeal nerves. These voice disorders spontaneously resolve in the period from 2 to 6 months after the operation. The effectiveness and safety of therapy for postoperative hypothyroidism, the correct selection of the dose of L-thyroxine depends not only on the level of TSH, but also on the genetic characteristics of the patient. Pharmacogenetic testing allows predicting the effectiveness of hypothyroidism correction. The quality of life after thyroidectomy is generally worse than after organ-preserving operations. To a large extent, it is determined by hypothyroidism. In the long term, the quality of life after thyroidectomy approaches the estimates of patients after organ-preserving operations. For an adequate assessment of the results of the operation, it is necessary to analyze the results no earlier than 1 year later.

[SUBACUTE THYROIDITIS AND COVID-19 (REVIEW)].

The COVID-19 pandemia has shown that there is not enough knowledge today to fully control it. Along with severe respiratory syndrome, attention has recently been paid to extrapulmonary lesions, including endocrinopathies. The aim of the study was to summarize the current literature data about the effects of the SARS-CoV-2 coronavirus on the thyroid gland. One of the most striking manifestations of viral aggression is de Quervain's subacute thyroiditis. The analysis of works from the most authoritative international abstract bibliographic databases was carried out using methods of analysis and processing of scientific resources. Based on the analysis, it was concluded that subacute thyroiditis can be both a clinical manifestation and a complication of COVID-19. The SARS-CoV-2 coronavirus can also trigger other thyroid diseases. The causes of subacute thyroiditis are considered to be the direct effect of the SARS-CoV-2 coronavirus on thyroid cells due to the use of ACE2 receptors, the subsequent inflammatory reaction and apoptosis, as well as central hypothalamus-pituitary mechanisms. The clinical variants of subacute thyroiditis in COVID-19 are diverse and have not been fully evaluated. In this regard, it can be concluded that the true incidence of subacute thyroiditis in COVID-19 is much greater, since it is masked by severe lesions of other organs.

[Regulation of IL33 Gene Expression by SP1 and Foxa1 in Breast and Lung Cancer Cells].

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family, primarily known as a mediator of the humoral immune response. It provides protection of barrier tissues and participates in the development of a range of diseases. This cytokine promotes carcinogenesis by induction of proliferation and survival of cancer cells, remodeling of the tumor microenvironment, and promoting immunosuppressive conditions. Elevated levels of IL-33 were observed in many types of cancers. This elevation correlates with a poor prognosis, making IL33 a promising target for cancer immunotherapy. The mechanisms of IL-33 expression regulation in human tumor cells are not well understood. Here, we show that that expression of IL-33 in breast and lung cancer cell lines depends, at least in part, on the activity of the SP1 and FOXA1 transcription factors. Increases in the activity of these transcription factors may be responsible for elevated levels of IL-33 and subsequent tumor progression.

[Nutritional status of preschool children of Moscow megalopolis at the beginning of the 21st century (somatometric aspects)].

Obesity is one of the most important and actual problems of public health, of healthcare, which dramatically expanded through the latest four decades. The aim of the study was the analysis of physical conditions of Moscow preschoolers at the beginning of 21th century as the indicator of nutritional status in «obesogenic¼ environment of megalopolis. Material and methods. Complex anthropometric study of children attending kinder gardens in Moscow (aged 3-7 years) was held in 2005-2006 (n=759). Literature data on samples of the 1970s were used for comparison. Anthropometric measurements were used to calculate personal values of body mass index (BMI, kg/m2). The more detailed estimation of somatic specificity of children included calculation of average values of standardized differences of each single body dimension of material of 2005-2006 from the values of samples of the 1970s. Results and discussion. The distribution of BMI of Moscow preschoolers at the beginning of 21th century (13.6% were overweight and 7.5% were obese) is quite comparable to the results of other population studies in Russia and around the world. The circumferences, mediated by adipose tissue, and skinfolds of modern Moscow preschoolers showed very significant increase of average standardized levels of dimensions (0.9-1.1 standard deviations as compared to the data of the 1970s). The comparison with the results of the similar study of Moscow school children allows, probably, to speak about the existence of accumulation effect as the mechanism of obesity development in the age aspect. Conclusion. The effect of the significant and valid increase of adiposity in preschoolers, combined with very modest changes of the size and shape of skeletal/muscle system and even its relative weakening was shown based on the results of the survey of Moscow preschoolers, conducted in 2005-2006, in comparison with the series of the 1970s.

[Leptin and leptin receptor evaluation in atherosclerotic plaques in patients with type 2 diabetes mellitus].

BACKGROUND: Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction. AIM: Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes. MATERIALS AND METHODS: We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared. RESULTS: No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively). CONCLUSION: Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

[Mineral metabolism and COVID-19: is there a connection?]

Due to global spread of COVID-19, the search for new factors that could influence its clinical course becomes highly important. This review summarize the relevant publications on the association between immune system and the main regulators of mineral homeostasis including. In addition, we have highlighted the various aspects of phosphorus-calcium metabolism related to the acute respiratory diseases and in particular to COVID-19. The data about the calcium-phosphorus metabolism in SARS-CoV-2 infection is required to understand the possible clinical implications and to develop new therapeutic and preventive interventions.

[Optical sonography in differential diagnosis of thyroid nodes]. / Optosonografiya v differentsial'noi diagnostike uzlovykh obrazovanii shchitovidnoi zhelezy.

OBJECTIVE: To develop a non-invasive method for differential diagnosis of thyroid nodes. MATERIAL AND METHODS: Optical sonography was made in 623 patients with thyroid nodes including 374 women (60%) and 249 men (40%) aged 19-79 years (mean 64±15 years). All patients underwent ultrasound-assisted fine-needle aspiration biopsy. Cytological examination revealed cystic colloidal goiter (CCG) in 317 (51%) cases, follicular adenoma (FA) - in 197 (31.5%) cases, thyroid cancer - in 109 (17.5%) cases. All patients underwent surgery. Histological examination verified cystic colloidal goiter in 354 (56.8%) cases, follicular adenoma - 75 (12.0%) cases, thyroid cancer - 194 (31.2%) cases. Follicular cancer was diagnosed in 120 cases, papillary cancer - 70 cases, undifferentiated cancer - 4 cases. RESULTS AND CONCLUSION: Sensitivity, specificity and accuracy of optical ultrasonography in differential diagnosis of thyroid nodules were estimated. Sensitivity of ultrasonography in the diagnosis of thyroid malignancies was 0.75, specificity 0.62, accuracy 0.67. Sensitivity of ultrasonography in the diagnosis of thyroid adenoma was 0.85, specificity 0.62, accuracy 0.73. Sensitivity of optical sonography in the diagnosis of CCH was 0.62, specificity 0.61, accuracy 0.7. Optical sonography ensures differentiation of CCH and follicular adenoma, CCH and thyroid cancer, follicular adenoma and thyroid cancer. Sensitivity, specificity and accuracy of ultrasonography in differential diagnosis of FA and thyroid cancer are 0.85, 0.62, 0.73 and 0.8, 0.71, 0.7, respectively.

[Interleukin-33: Friend or Enemy in the Fight against Tumors?]

Interleukin-33 (IL-33) belongs to the IL-1 cytokine family and acts as a danger signal. IL-33 is released from stressed or necrotic cells. Initially, IL-33 was described as an inducer of the humoral immune response, which activated Th2 cells and mast cells involved in modulating inflammation and allergic reactions. In addition, IL-33 acts as a stimulator of the Th1, NK, and CD8T cells, which induce a cytotoxic immune response against intracellular pathogens. It was recently discovered that this cytokine is involved in the development of cancer by performing both pro- and antitumor functions. IL-33 can directly affect tumor cells and provokes their proliferation, survival, and metastasis. Moreover, IL-33 stimulates carcinogenesis by remodeling the tumor microenvironment and inducing angiogenesis, thus contributing to the generation of immunosuppressive conditions. At the same time, IL-33 causes tumor infiltration with cytotoxic CD8 T lymphocytes and natural killers, which leads to cytolysis-mediated cancer cell death. This review describes the versatile role of the IL-33/ST2 cascade in the development of experimental and clinical tumors. In addition, we discuss the prospects for the application of IL-33 and ST2 as diagnostic biomarkers and targets for cancer immunotherapy.

[The use of confocal microscopy in experimental studies and clinical practice of an endocrinologist: modern opportunities].

Confocal microscopy is a modern imaging method that provides ample opportunities for in vitro and in vivo research. The clinical part of the review focuses on well-established techniques, such as corneal confocal microscopy for the diagnosis of diabetic neuropathy or endocrine ophthalmopathy; new methods are briefly described (intraoperative evaluation of tissues obtained by removing pituitary adenomas, thyroid and parathyroid glands). In the part devoted to fundamental research, the use of confocal microscopy to characterize the colocalization of proteins, as well as three-dimensional intracellular structures and signaling pathways in vivo, is considered. Indicators of intracellular calcium are analyzed.

[Ultrasound assessment of vocal cords function after thyroid surgery]. / Pervyi opyt otsenki funktsii golosovykh sviazok ul'trazvukovym metodom issledovaniia u bol'nykh posle operatsii na shchitovidnoi zheleze.

OBJECTIVE: To analyze vocal cords function after thyroid surgery by using of ultrasound examination. MATERIAL AND METHODS: Assessment of voice quality according to GRBAS scale, ultrasound examination of vocal cords and indirect laryngoscopy were performed in 57 patients after thyroid surgery. RESULTS: Postoperative indirect laryngoscopy and ultrasound revealed normal mobility of vocal cords in all patients. However, 98.3% of patients subjectively noted deterioration of voice quality due to hoarseness and fatiguein early and long-term period, respectively. Complete restoration of vocal function occurred after 6 months postoperatively. Impaired voice quality is probably due to edema of vocal cords after intubation that is manifested by unclear contours during ultrasound. Ultrasound is useful to diagnose shortening and displacement of paretic vocal cords. CONCLUSION: Ultrasound of vocal cords could be alternative to indirect laryngoscopy for postoperative assessment of vocal cords function in patients after thyroid surgery.