[Primary Generalized Glucocorticoid Resistance: a case report].

Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.

[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.

[Thyrotropin-secreting pituitary adenomas: clinical features and results of treatment in 45 patients].

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSH-PA) are a rare cause of thyrotoxicosis and account for 0.5-2% of all pituitary adenomas. Taking into account the rarity of the disease, it is extremely important to analyze each case of TSH-PA. AIM: To analyze the clinical characteristics and treatment outcomes of patients with TSH-PA, as well as to determine preoperative and early postoperative factors that predict long-term remission. MATERIALS AND METHODS: In a single-center retrospective study we analyzed clinical signs, laboratory and instrumental studies, as well as the treatment outcomes of patients with TSH-PA from 2010 to 2023. Preoperative factors, as well as TSH level measured on day 3 postoperatively, were evaluated for their ability to predict long-term remission when comparing groups of patients with and without remission. RESULTS: The study included 45 patients with TSH-PA (14 men, 31 women), with a median age of 45 years [30; 57]. The most common clinical manifestations of TSH-PA were: cardiac arrhythmia in 37 (82.2%) patients, thyroid pathology in 27 (60%), neurological disorders in 24 (53.35%). Most PAs were macroadenomas (n=35, 77.8%). Preoperatively, 28 (77.8%) patients received somatostatin analogs, and 20 (71.4%) patients were euthyroid at the time of surgery. Surgical treatment was performed in 36 (80%) patients, postoperative remission was achieved in 31 cases (86.1%). Administration of somatostatin analogues to patients with no remission/relapse after surgery lead to the remission in 100% of cases (4/4). A 1 mm increase in PA size raised the odds of recurrence/no remission by 1.15-fold,and PA invasion during surgery - by  5.129 fold. A TSH level on day 3 postoperatively above 0.391 mIU/L (AUC, 0.952; 95% CI 0.873-1.000; standard error 0.04; p<0.001) identifies patients with relapse/absence of remission after surgical treatment (sensitivity = 100%, specificity = 88.9%). CONCLUSION: The TSH-PA in the structure of PAs is extremely rare, and as a result, most of them are misdiagnosed and detected already at the stage of macroadenoma. The most effective method of treatment is transnasal transsphenoidal adenomectomy. Somatostatin analogues can be used as second-line therapy if surgical treatment is ineffective. We have proposed a possible model for postoperative TSH levels (>0.391 mU/l) to predict recurrence of TSH-PA, which requires validation on an expanded number of cases.

[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.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

[Regional target program «Prevention of iodine deficiency diseases for 202X-202X¼].

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[Immunogenetics of primary hyperaldosteronism: fundamental studies and their clinical prospects].

Primary hyperaldosteronism (PHA) is the most common form of endocrine hypertension. Until recently, the reason for the development of this condition was believed to be the presence of genetic mutations, however, many studies declare that the disease can be polyetiologic, be the result of genetic mutations and autoimmune triggers or cell clusters of aldosterone-producing cells diffusely located in the adrenal gland at the zona glonerulosa, zona fasculata, zona reticularis, as well as directly under the adrenal capsule. Recently, the actions of autoantibodies to type 1 angiotensin II receptors have been described in patients with renal transplant rejection, with preeclampsia, and with primary hyperaldosteronism. The diagnostic role of antibodies in both forms of PHA (aldosterone-producing adenoma and bilateral hyperaldosteronism) requires clarification. Diagnosis and confirmation of the focus of aldosterone hypersecretion is a multi-stage procedure that requires a long time and economic costs. The relevance of timely diagnosis of primary hyperaldosteronism is to reduce medical and social losses. This work summarizes the knowledge about genetic mutations and presents all the original studies devoted to autoantibodies in PHA, as well as discusses the diagnostic capabilities and limitations of the available methods of primary and differential diagnosis of the disease and the prospects for therapy.

[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.

[Dynamics of epidemiological indicators of thyroid pathology in the population of the Russian Federation: analytical report for the period 2009-2018].

BACKGROUND: The level of iodine consumption by the population largery determines the spectrum of thyroid pathology. To date, in the Russian Federation, iodine-deficiency disorders (IDD) occupy a leading position in the structure of all thyroid diseases. Chronic ID leads to adverse health consequences and significant economic costs for their elimination on a national scale. However, the spectrum of thyroid pathology is not limited to the problem of ID, and the study of other thyroid diseases is also of interest. AIMS: to assess the dynamics of prevalence and incidence of IDD and other thyroid diseases in the entire population of the RF for the period 2009-2018, using official state statistics. MATERIALS AND METHODS: the main epidemiological indicators (incidence and prevalence) of thyroid diseases in the entire population of the RF were analyzed using official state statistics. The analyzed period is 2009-2018. There was no medical intervention. To assess the dynamics of prevalence and incidence, a linear regression models were constructed, the slope of the trend line was calculated. RESULTS: the data were analyzed in accordance with the structure of diseases presented in the statistical reporting: goiter, thyroiditis, hypothyroidism, thyrotoxicosis, congenital iodine deficiency syndrome. For the ten-year period 2009-2018 there is a statistically significant increase in the prevalence of various forms of goiter, thyrotoxicosis, congenital iodine deficiency syndrome in the entire population of the Russian Federation. During the observation period, an increase in the incidence of thyrotoxicosis was revealed. With regard to the incidence of congenital iodine deficiency syndrome, only an upward trend was revealed. Despite the fact that during the observation period the number of new cases of various forms of goiter decreased, the prevalence of goiter among the population of the Russian Federation remains high: 1.2% of the population by January 1, 2019. with the growth of autoimmune pathology, improvement of the level of diagnosis, and also, in some cases, with overdiagnosis (for example, when diagnosing autoimmune thyroiditis in individuals with asymptomatic carriage of antithyroid antibodies). The current approaches to iodine prophylaxis are not effective enough. CONCLUSIONS: the results of the analysis indicate mainly an increase in the high prevalence of thyroid pathology among the population of the RF against the background of regional events. The problem of ID remains unresolved, which dictates the need to introduce universal mandatory salt iodization in the territory of the RF.

[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.

Somatic Mutations in the BRAF, KRAS, NRAS, EIF1AX, and TERT Genes: Diagnostic Value in Thyroid Neoplasms.

The feasibility of using molecular genetic markers associated with thyroid neoplasms and more aggressive course of the disease is now actively studied. We analyzed the diagnostic value of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX, and TERT genes in histological material from 153 patients with thyroid gland neoplasms. BRAF mutations (exon 15, codon area 600-601) were found in 54 patients, NRAS mutations (exon 3, codon 61) were detected in 12 patients; mutations KRAS, TERT, and EIF1AX genes were not detected.

[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.

[Aldosterone- and cortisol-co-secreting adrenal tumors: an uneasy sum of well-known parts (review)].

Primary aldosteronism (PA) is the most common form of secondary arterial hypertension. In patients with PA, more so than in the general population, there is a prevalence of insulin resistance, diabetes mellitus, metabolic syndrome, osteoporosis, and symptoms of depression; these conditions are more likely to manifest a gluco- rather than mineralocorticoid excess. This fact is of particular importance in light of recent studies that have shown that PA is often associated with glucocorticoid excess. Since the first reports of cases of combined secretion of aldosterone and cortisol in 1979, the number of cases of so-called Connshing syndrome has increased. An analysis of data from recent studies suggests that hypercortisolism in PA is closely associated with an increased risk of cardiovascular complications, metabolic disorders and post-surgical adrenal insufficiency. The most important diagnostic problem in adenomas with combined secretion is the risk of false interpretation of the results of adrenal venous sampling (AVS). The indications that suggest aldosterone-and-cortisol-co-producing adenoma are the lack of suppression of cortisol levels following a night test with 1mg of dexamethasone, and an adrenal tumo of over 2.5cm. As an alternative test capable of differentiating this type of tumor, a number of researchers have proposed measuring the level of so-called hybrid steroids in the peripheral plasma and urine. Taking into account the high prevalence and potential risks, ruling out of excess corisol secretion is obligatory in all cases of PA before AVS and when planning surgery.

[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.

[Adiponectin and parameters of glucose and lipid metabolism at different clinical and morphological stages of non-alcoholic fatty liver disease in patients with abdominal obesity].

AIM: To compare clinical, laboratory, and morphological parameters in patients with abdominal obesity and non-alcoholic fatty liver disease (NAFLD) and to assess the relationship between the degree and stage of the disease and the cardiometabolic risk factors of type 2 diabetes mellitus and cardiovascular diseases. SUBJECTS AND METHODS: Eighty patients aged 30 to 50 years with abdominal obesity were examined. NAFLD was diagnosed after liver puncture biopsy. The parameters of carbohydrate and lipid metabolism and the activity of hepatic transaminases and the protective adipocytokine adiponectin were investigated. RESULTS: NAFLD was verified in 77 examinees. Metabolic disturbances were found in the majority of the examinees with abdominal obesity and NAFLD; they were concurrent and increased in their rate and degree with the progression of NAFLD, obesity, and insulin resistance. The patients with NAFLD had a significantly decreased adiponectin level that got worse as NAFLD progressed. CONCLUSION: The investigation has revealed that NAFLD is associated with cardiometabolic disorders (dyslipidemia, carbohydrate metabolic disturbances, and insulin resistance) increasing in their rate and degree with the progression of NAFLD and the lower adiponectin level reducing as NAFLD worsens.

[Thyroid dysfunction and the hemostatic system].

Whether there is a link between thyroid dysfunction and different impairments in the hemostatic system is discussed. The level of thyroid hormones is an essential factor that influences the coagulation system. Thyroid dysfunction affects the balance between coagulation and fibrinolysis, by increasing the risk of thrombosis and hemorrhage in hyperthyroidism. However, there is no consensus of opinion regarding the mechanisms of the described hemostatic changes in the literature.

[The results of the "tiromobil" epidemiological trial of pregnant women in the Russian Federation].

AIM: To study structural and functional changes in the thyroid gland (TG) in pregnant women living in iodine-deficiency regions; to evaluate efficacy of prophylactic measures. MATERIAL AND METHODS: Random sample method was used for examination of 1090 pregnant women living in the regions with different iodine provision. All the participants were examined clinically, measurements were made of thyroid size, TTH, free T4, iodinuria. RESULTS: Iodine salt in household was used only by 17% women. Prophylaxis of iodine deficiency was conducted in 51% pregnant women. Thyroid alterations were detected in 27% examinees, diffuse goiter was diagnosed on the average in 17% pregnant women (in some regions 36%), nodular goiter--in 3.1%, focal goiter alterations of the thyroid--in 4.4%, symptoms of autoimmune thyroid disease--in 2.7%. ldoinuria varied with regions from 72.5 to 150 mcg/l. TTH and T4 levels were mainly normal. Isolated fall of T4 in trimester II and III was registered in 70% pregnant women, low TTH--in 4.4%. CONCLUSION: Most of the pregnant women in the regions studied were at risk of diseases associated with iodine deficiency. Prevention of iodine deficiency is not adequate.

[Disturbances of thyroid function after coronary angiography].

Frequency of thyroid gland functional disturbances after introduction of iodine-containing radiographic contrast agents during coronary angiography was studied in 146 patients, residents of the zone of borderline iodine deficit. Frequency of thyroid pathology was high at baseline (39%). Functional state of the thyroid gland was assessed before and 1, 3, 6, 12 months after investigation. During first month after coronary angiography there were several new cases of thyrotoxicosis and hypothyroidism, as well as deterioration of preexisting functional disturbances of the thyroid. Patients with baseline pathology and functional disturbances of thyroid gland before conduction of coronary angiography should be included into risk group of development of iodine induced states.

[Diagnostics, treatment, and prevention of iatrogenic iodine-induced thyroid gland diseases].

The authors of the study investigated the effects of pharmacological doses of iodine as an ingredient of amiodaron, an anti-arrhythmic agent, and iodine radiopaque contrast agents (RCA), on the thyroid gland (TG) function. The subjects were 133 patients aged 60.5 +/- 8.5 years, who had been taking amiodaron for 12 to 164 months, and 164 patients aged 59.4 +/- 9.1 years, who were examined before coronarography (CAG) with RCA, and 1, 3, 6, and 12 months after the procedure. Serum levels of TSH, FT4, FT3, TG antibodies, TPO antibodies, and urine iodine level were measured; TG ultrasonography was performed. Forty-nine (51.9%) out of the 133 patients on amiodaron therapy developed thyroid disfunction. Subclinical hypothyroidism (24 cases; 18%) and manifest thyrotoxicosis (21 case; 15.8%) prevailed among functional TG disorders. Thirty-one per cent of the patients with thyrotoxicosis had preceding TG diseases; 70% of the thyrotoxicosis patients had a cardiac arrhythmia relapse. The concentration of thyroid antibodies did not change in patients with normal TG. The patients who underwent CAG displayed elevated renal iodine excretion 1, 3, and 6 months after RCA administration. Thyroid disfunction (thyrotoxicosis in 7.6% of the cases; hypothyroidism in 15.8% of cases) was revealed in 23.4% of the patients with preceding TG diseases one month after CAG. Cardial pathology exacerbation was observed in patients with thyrotoxicosis.