[Development of destructive thyroiditis and diabetes mellitus after three injections of pembrolizumab for skin melanoma].

The exponential rise in the use of immune checkpoint inhibitors (Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, and Avelumab) as the new standard for cancer treatment increase the incidence the immune-related adverse events due to immune activation. Endocrine immune-related adverse events are the third most commonly reported. Thyroid gland is most susceptible to autoimmune dysfunctions from immune checkpoint inhibitors and associated with the use of anti-PD-1 monoclonal antibodies. Hypophysitis develops more often during therapy with anti-CTLA-4 monoclonal antibodies. But such immune-related adverse events as diabetes mellitus, hypoparathyroidism are rare (about 1% of cases).We present a clinical case of the patient with skin melanoma who was prescribed therapy with immune checkpoints inhibitors (Pembrolizumab). Immune-related adverse events developed with damage to the endocrine organs after 3 Pembrolizumab injections. Of greatest interest is the development of two endocrine immune-related adverse events at once: destructive thyroiditis (with a short phase of thyrotoxicosis and subsequent persistent hypothyroidism) and diabetes mellitus. We tried to reflect the chronology of diseases and their features as fully as possible for endocrinologists, oncologists, therapists, family doctors and other medical doctors of related specialties.

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

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

[Differential diagnosis between autoimmune thyrotoxicosis and thyroid hormone resistance syndrome: clinical case report].

We report a case of 50-year-old woman with thyroid hormone resistance syndrome. For 20 years this patient have been treated for autoimmune thyrotoxicosis: she underwent thyroid surgery and then was on thyroid-blocking therapy. Repeated laboratory tests demonstrated elevated serum thyroid hormones concentrations and elevated TSH concentration. Inappropriate TSH secretion became the reason for conducting further investigations. In those cases, the diagnostic approach is complicated and cases may be referred as a syndrome of thyroid hormones resistance or as a pituitary mass. Results of magnetic resonance imaging as well as results of octreotide test did not confirm TSH-producing pituitary adenoma. Lack of consistent thyrotoxicosis symptoms and normal level of biochemical markers that reflect peripheral tissue response to excessive thyroid hormones action were regarded as an evidence for thyroid hormones resistance syndrome. In cases of thyroid hormone resistance syndrome, there is no reduction in thyroid hormones after octreotide administration and we could observe it in our patient. Thereby clinical data and laboratory tests supported the diagnosis of thyroid hormone resistance syndrome. To establish definitive diagnosis and to verify genetic cause of the disease we performed direct sequencing of the THRB gene exons 9-10.

[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.

[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.

[Abnormal calcium metabolism in the remote period after bariatric surgery].

Calcium metabolism in the long-term period after bariatric surgery is reviewed in the present article. The study of calcium metabolism parameters and vitamin D status was performed in The Endocrinology Research Center. Morbidly obese patients (BMI > 40) were included in the 1st group (n = 22), patients who underwent biliopancreatic diversion for morbid obesity (n = 23) were included in the 2nd group, healthy normal weight controls (n = 22) were included in the 3rd group. 25 (OH) D level was different in the 3 groups (p < 0.001). Vitamin D deficiency prevailed in morbidly obese patients compared to healthy controls (p = 0.007). Elevated parathyroid hormone (PTH) level was found in 4 (18%) morbidly obese patients, in 12 (52%) operated patients. Not a single case of PTH over reference interval was found in the controls. The frequency of secondary hyperparathyroidism was significantly higher in the operated patients.

[Diagnostics and treatment of polyglandular syndrome of adults].

Autoimmune polyendocrine syndromes (APS) are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune diseases. APS comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS type 1) and a more common adult type with (APS 2) or without adrenal failure (APS 3). The first clinical manifestations of APS 1 usually occur in childhood whereas APS 2 mostly occurs during the third and fourth decades of life. The third type has been described in adults that, contrary to types 1 and 2, does not involve the adrenal cortex. No clinical differences between types 2 and 3 have been described except the absence of adrenal failure. Type 4 APS is a rare syndrome characterized by the combination of autoimmune conditions not falling into the above categories. It consists of adrenal failure with one or more minor autoimmune disorders barring major components of type 1 and 2 APS. Usually, autoimmune polyendocrine syndrome of adults manifests itself as one of the major autoimmune diseases (such as adrenal failure, Grave's disease, or type 1 diabetes) and minor autoimmune disorders (vitiligo, alopecia) preceding the development of autoimmune deficiency of major endocrine glands. This article describes a patient with type 3 APS, who developed type 1 diabetes. Grave's disease and vitiligo. The development of the syndrome started from vitiligo in the chidhood. Moreover, the patient suffered primary sterility and presented with progressive diabetic nephropathy of autoimmune origin. It is concluded that patients with a single autoimmune component of polyendocrine syndrome should be screened to exclude other autoimmune endocrine disorders.

[Influence of genetic factors on the result of therapy for diffuse euthyroid goiter].

The purpose of the present study was to investigate a relationship between the distribution of genotypes of the polymorphic markers TSHR (rs3783949, A/C substitution), NIS (rs7250346, C/G substitution), DUOXI (rs2467825, A/G substitution), DUOX2 (rs71713669, G/T substitution), and TRO (rs!7091737, G/T substitution) genes and the result of treatment for diffuse euthyroid goiter (DEG) using two regimens: monotherapy with iodine preparations and combined therapy with iodine and levothyroxine. To identify a more effective and safe treatment for DEG, the authors compared thyroid volume, the levels of pituitary thyroid-stimulating hormone and thyroid peroxidase antibodies in two groups: 1) monotherapy with KI (200 pg/day) (n = 40) and 1) combined therapy with KI (100 pg) + L-T4(lpg/kg/day) (n = 41). According to the result of treatment, each group was divided into 2 subgroups: "fair result" and "poor result" (the thyroid volume failed to achieve the normal range or continued to increase). Correlation analysis was made to assess a relationship between the polymorphism of the genes and the result of therapy for DEG. There was a significant correlation between the distribution of genotypes of the polymorphic marker the TSHR gene and the result of treatment for DES in the monotherapy group: there were prevalent AA + AC and CC genotypes with fair and poor results, respectively. There was no significant correlation between the distribution of the genotypes of the study polymorphic markers and the result of treatment using the combined therapy. Thus, the result of treatment for DES via monotherapy with iodine preparations may depend on genetic factors.

[Follicular thyroid neoplasia (a lecture)].

Nodular thyroid formations are detected in approximately 4-7% of individuals living in regions with normal iodine supply. In regions of iodine deficiency, the prevalence of nodular goiter is significantly higher, especially in women older than 40 years, in which it can exceed 30%.

[Results of epidemiological surveys for iodine-deficiency diseases within the framework of the Thyromobile project].

In the Russian Federation, there are virtually all areas whose population is at risk for iodine-deficiency disorders. During 2003, we made epidemiological studies of iodine-deficiency disorders within the framework of the Thyromobile project supported by the pharmaceutical company "Nycomed"in 12 regions of the Russian Federation. A total of 2673 individuals were examined. According to the WHO recommendations, the study covered prepubescent children aged 8 to 11 years. It involved physical examination, thyroid ultrasound study, blood sampling for ioduria, intelligence test, and sodium chloride iodine assay. The findings indicated that the tension of goiter endemia corresponded to the level of iodine deficiency, which was in the range of mild iodine deficiency, in most regions other than some districts of the Volgograd, Astrakhan, Nizhni Novgorod regions where the median of ioduria in schoolchildren corresponded severe iodine deficiency. The studies indicated that the population's use ofiodinated salt is not up to the recommendations of international expert organizations. Intelligence tests revealed an 11-18% IQ decrease in children from virtually all study areas. According to the strategy of iodine deficiency control in the Russian Federation, it is advisable to use iodinated salt for mass prevention and drugs containing a physicological dose of iodine for group and individual prevention.

[Thyroid structural changes: results of a screening ultrasound study of a Moscow population].

То assess the prevalence and pattern of thyroid disease in Moscow, a mild iodine-deficiency area, the authors examined a random sample of 1103 individuals (1004 females and 99 males) during 14 months. The examinees' age ranged from 17 to 80 years; the mean age was 36.7±14.05; median was 37 years. The survey involved a physical examination with thyroid palpation, brief history data collection, and thyroid ultrasound study on a "Mysono"portable apparatus with a 7.5-MHz linear transducer, operating on a real-time basis. Among the examinees the echographic signs of these or those thyroid changes were found in 36% of cases. The most common abnormalities were focal thyroid tissue changes, whose prevalence was 12.4%. Thyroid nodular masses were encountered at a slightly less frequency (10.5%). Of them, nodular and multinodular goiter accounted for 6 and 4.5%, respectively. The third group of changes is presented by a diffuse decrease in thyroid tissue echogenicity (9%). Diffuse goiter was less frequently identified; its frequency was 5%. A minor proportion (0.1%) of the examinees had a history of operations for this or that thyroid disease.

[Clinical guidelines developed by the Russian Association of Endocrinologists for the diagnosis and treatment of nodular goiter].

The guidelines presented do not pretend to be a systematic presentation of all aspects of the diagnosis and treatment of nodular goiter and are not intended to replace guidelines for various medical disciplines. In real clinical practice, situations may arise that are beyond the scope of the recommendations presented, in connection with which the final decision regarding a specific patient and responsibility for him lies with the attending physician.The recommendations presented are mainly devoted to the diagnosis and treatment of nodular (multinodular) euthyroid colloid, differently proliferating goiter in adults (over 18 years of age) and are the agreed opinion of the RAE experts who developed them. Nodular (multinodular) toxic goiter, tumors (malignant and benign), as well as other diseases that can manifest themselves by nodular formations of the thyroid gland (thyroid gland), are discussed mainly in the context of differential diagnosis. The recommendations also do not affect the features of diagnosis and treatment of nodular goiter in children and adolescents.