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Background: Sodium glucose co-transporter type 2 inhibitors (iSGLT2) are antihyperglycemic drugs approved for the treatment of type 2 diabetes mellitus (T2DM). Clinical trials with these drugs have shown evidence of an increased risk of fractures and an effect on phosphorus, vitamin D and parathyroid hormone (PTH) levels.Aim: The aim of this study was to investigate the effect of the most selective iSGLT2 empagliflozin on the calcium and phosphorus metabolism in patients with T2DM and preserved kidney function.Materials and methods: Thirty-nine T2DM patients were received empagliflozin 10 mg in addition to their antihyperglycemic drugs for 12 weeks. Before starting treatment, a dual-energy X-ray absorptiometry (DXA) with an assessment of the trabecular bone score (TBS) was performed. The concentration of phosphorus (P), total (tCa) and ionized calcium (Ca++), fibroblast growth factor 23 (FGF-23), 25(OH)D and PTH were assessed.Results: According to the DXA results, only 2 patients had osteoporosis, 10 (25.6%) patients had bone mineral density (BMD) values below 1.35 g /cm2 on the TCI scale. Treatment with empagliflozin for 12 weeks was lead to significant increase in FGF-23. Compared to the baseline level, there were no statistically significant differences in the concentrations of P, oCa, Ca++, PTH and 25(OH)D after 12 weeks of treatment. The level of FGF-23 did not correlate with the level of glomerular filtration rate either before or after treatment (r = 0.31, p = 0.27 and r = 0.39, p = 0.55, respectively). In addition, baseline BMD adjusted for TBS and baseline 25(OH)D did not correlate with Ca, F, FGF-23, and PTH concentrations (p>0.05).Conclusion: Thus, empagliflozin has increased the level of FGF-23 without significant changes in the concentration of phosphorus, calcium, 25 (OH) D, and PTH after 12 weeks of treatment in patients with T2DM and preserved renal function. The obtained data confirmed the necessity to assess the TBS in patients with T2DM, because it’s provide additional information on the quality of bone tissue.

To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly.A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery.Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%).The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.Цель.Изучение возможности использования базального уровня гормона роста (ГР) через 24 ч после операции для прогнозирования результатов хирургического лечения акромегалии. Материалы и методы.В проспективное когортное исследование включили 45 пациентов с впервые выявленной акромегалией. Степень параселлярного роста аденомы гипофиза оценивали на предоперационной магнитно-резонансной томографии хиазмально-селлярной области с использованием классификации Knosp. Все больные перенесли транссфеноидальную аденомэктомию, выполненную одним нейрохирургом. Через 24 ч после операции определяли базальный уровень ГР. Оценку эффективности хирургического лечения акромегалии проводили через 12 мес. Результаты.Через 12 мес после транссфеноидальной аденомэктомии ремиссия акромегалии достигнута у 19 (42%) из 45 пациентов. Прогностическая значимость таких параметров, как размер аденомы и характер параселлярного роста, оказалась невысокой: наличие микроаденомы гипофиза показало низкую чувствительность (31,6%), а Knosp Grade 02 низкую специфичность (38,5%) в отношении развития ремиссии акромегалии. Значение базального уровня ГР через 24 ч после операции 1,30 нг/мл оказалось оптимальной точкой разделения в отношении прогноза ремиссии акромегалии с чувствительностью 96,2% (95% доверительный интервал 81,199,8%) и специфичностью 84,2% (95% доверительный интервал 62,494,4%). Заключение.В исследовании продемонстрирована возможность использования определения ГР через 24 ч после операции как предиктора ремиссии акромегалии. Уровень ГР1,30 нг/мл через 24 ч после операции имеет бльшую прогностическую значимость по сравнению с наличием микроаденомы гипофиза и Knosp Grade 02 в отношении прогнозирования ремиссии акромегалии. Для подтверждения полученных данных необходимы дальнейшие исследования с большим числом наблюдений.

The infectious disease COVID-19, induced by virus SARS-CoV-2, is associated with high morbidity and mortality. Considering the COVID-19 pandemic since the beginning of 2020, the recognition of its risk and prognostic factors with the identification of the most vulnerable groups of population is highly relevant. The relationship between the severity of COVID-19 and diabetes mellitus, hypertension, and cancer has been confirmed. The management of patients with concomitant somatic pathology during the development of COVID-19 is widely discussed. Obesity is one of the most common noninfectious diseases in modern society, which can directly and indirectly aggravate the course and increase mortality from COVID-19. Obesity is also considered a risk factor for COVID-19 morbidity and mortality. This review presents data on the effects of obesity on the coronavirus infection and the management of obese patients during the COVID-19 pandemic.

During the COVID-19 pandemic, the efforts of many researchers around the world are aimed at finding preventive and prophylactic measures as well as therapeutic agents against SARS-CoV-2. Recent studies have showed that vitamin D deficiency could be one of many factors associated with the development and severity of acute respiratory infections, and vitamin D could be used for prevention and treatment of these patients. This review summarizes data about the role of vitamin D in the pathogenesis and prevention of respiratory viral infections, including new coronavirus infection as well as mechanisms for reducing the risk of infection with vitamin D therapy. Probably, this review will be of interest for endocrinologists and other specialists.

BACKGROUND: The association between vitamin D deficiency and the severity of COVID-19 is currently being actively discussed around the world.AIM: The aim of this study was to assess the prevalence of vitamin D insufficiency and deficiency and compare it with the incidence rates of SARS-CoV-2 in eight Federal Districts of the Russian Federation.MATERIALS AND METHODS: We included 304,564 patients (234,716 women; 77,1%) with serum 25(OH)D levels results performed September 2019 through October 2020.RESULTS: Only 112,877 people (37.1%) had a normal serum 25(OH)D level, others had a deficiency. Vitamin D insufficiency and deficiency was presented with the same frequency in women and men, and no differences were found depending on the geographical location and age in subjects from 18 to 74 years old. However, subjects over 75 years more often had vitamin D deficiency, while subjects under 18 years had normal levels in over 50% cases. In addition, 21,506 patients were tested for SARS-CoV-2 by PCR with further comparison of results with serum 25(OH)D level. The SARS-CoV-2 positivity rate was detected in 3,193 subjects, negative in 18,313. There were no differences in the morbidity in a vitamin D deficiency and a normal level. Thus, 14.8% subjects had positive PCR rates among vitamin D deficiency patients (4,978 tests), 14.9% when 25(OD)D level was from 20 to 30 ng/ml (7,542 tests), 15.0% among those who had 25(OH)D 30- 50 ng/ml (6,622 tests), and 13.9% when vitamin D was more than 50 ng/ml (4,612 tests).CONCLUSION: There was no association between the COVID-19 incidence and vitamin D status in different regions of Russia. Although the nutrient deficiency persists in all regions and is most often diagnosed in people over 75 years old.

The aim of the study. To assess the role of early postoperative examination in the prognosis of cd remission 1 year after TSS.Patients and methods. 101 Patients (12 men, 89 women, mean age 41,2 years (15-72) with confirmed cd were included. Midnight and morning serum cortisol and plasma ACTH, late night salivary cortisol, 24-h urinary free cortisol (ufc) excretion were performed at the days 2-3 and 12-14 after the TSS. Hypercortisolism remission status was estimated one year after surgery. The optimal threshold values of ACTH and cortisol parameters at 2-3 and 12-14 days after surgery to prediction of cd remission after TSS were calculated by roc-analysis.Results. One year after surgery cd remission was confirmed in 63 patients, whereas in 38 patients hypercortisolism persisted. Postoperative parameters of cortisol and ACTH secretion had comparable high specificity and sensitivity at 2-3 and 12-14 days after surgery for prediction cd remission.Conclusion. According to our data, morning serum cortisol ≤388 nmol/l and plasma ACTH ≤20 pg/ml at 2-3 d after TSS may be used as a prognostic criterion for cd remission 1 year after surgery with sensitivity and specificity 94,9%, 75,9% and 83,3%, 95,8%, respectively.

Glycemic variability plays a crucial role in estimating the risk of diabetes complications, defining glycemic goals and evaluating the success of treatment in diabetes patients of all types. Yet there are many of shallowly studied and promising indexes depicting different characteristics of signals acquired from continuous glucose monitoring (CGM) systems. We analyzed various glycemic variability measures, including CONGA, LI, J-Index, LBGI, HBGI, GRADE, M-value, MODD, MAGE and ADRR among others, and evaluated them on a set of 247 weekly CGM records from gestational diabetes (GDM) patients and healthy pregnant women. In our study GDM patients were divided into two groups according to glycemic targets: tight control (7.0 mmol/L after meal, 5.1 mmol/L fasting) in the first group and less tight control (7.8 mmol/L after meal, 5.3 mmol/L fasting) in the second. The study has shown how various glucose variability indexes and features of CGM signals differ in GDM patients with different treatment goals and in healthy pregnant women.

Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile.This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used "The epidemiology of cardiovascular disease in different regions of the Russian Federation" study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex.Acromegaly patients had lower PWV (6.70 (5.75-7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70-8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73-8.60), p 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p 0.01; β = 0.09, p 0.01), obesity (r = 0.46, p 0.01; β = 1.36, p 0.01), systolic blood pressure (ρ = 0.60, p 0.01; β = 0.05, p 0.01), diastolic blood pressure (ρ = 0.62, p 0.01; β = 0.07, p 0.01), triglycerides (ρ = 0.55, p 0.01; β = 0.58, p = 0.04), glucose (ρ = 0.54, p 0.01; β = 0.70, p 0.01) and diabetes (r = 0.40, p 0.01; β = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = -0.49, p ≤0.01; β = -0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = -0.47, p = 0.01; β = -0.005, p ≤0.01) as well as with diuretics treatment (β = -1.17, p = 0.03).PWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly.

Background. The aim of our study was to estimate the association of lipid fractions and skin autofluorescence (AF), measured with experimental sample of fiber optic spectrometer FOS-1, in patients with diabetes mellitus (DM). Methods. We included in the study 44 type 1 DM patients (median age 29.5 (24.0; 36.0) and 23 type 2 DM patients, median age 58.0 (47.0; 61.0). Blood lipids and glycosylated hemoglobin (HbA1c) were analyzed. Skin AF was measured with fluorescence–reflection spectrometer FOS-1 at a wavelength of 460 nm with excitation of 365 nm. Ratio of fluorescent signal to signal of reflection in excitation region was used as measured parameter to reduce the effect of skin pigmentation. The measurements were carried out at 5 points on the skin area of forearms. Results. Type 1 DM group was divided to 13 dyslipidemic and 31 normolipidemic patients, subgroups were comparable by age, DM duration and HbA1c level. AF level in dyslipidemic and normolipidemic patients was 0.95 (0.82; 1.16) arb. units and 0.86 (0.79; 0.91) arb. units respectively, p=0.016. In type 1 DM group we found significant positive correlation between skin AF and total cholesterol level (R=0.45, р

Aim. To study the role of prognostic oral high-dose dexamethasone suppression test (HDDST) and pituitary MRI in the prognosis of Cushing’s disease (CD). remission after transsphenoidal endoscopic surgery (TSS). Material and methods. 59 patients with Cushing’s disease (9 men, 50 women, mean age 40 years (15-72) underwent TSS were included. Before the TSS HDDST and pituitary MRI were performed in all cases. Postoperative examination was done one year after surgery. Remission criteria were: combination of normal midnight serum cortisol levels, normal 24 hour urine free cortisol (UFC) excretion and serum cortisol suppression less than 50 nmol/l in 1-mg dexamethasone test or secondary adrenal insufficiency (the need for glucocorticoid replacement). The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was calculated by ROC-analysis. Results. One year after surgery CD remission was confirmed in 39 patients, whereas in 20 patients hypercortisolism persisted. The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was 72%. Test’s sensitivity and specificity were 82% and 84%, respectively. The probability of wrong prediction was 17% (p=0,0001). In our study, the results of TSS did not correlate with MRI adenoma size.

Prolactinomas are the most common of hormone secreting pituitary adenomas. Patients with prolactinomas generally have a benign prognosis. An algorithm is currently available for managing of this disease. Giant prolactinoma larger than 40 mm with severe invasive growth account for about 2—3% of the prolactin-secreting pituitary adenomas and evidence about management of such patients is limited. This case illustrates progress of a giant prolactin-secreting pituitary adenoma up to 70 mm in young male with a family history of prolactinomas in the absence of the adequate therapy for 8 years after initial diagnosis. After evaluation, it was decided to prescribe medical treatment. Cabergoline therapy started after evaluation appeared to be effective and had lead to significant decrease of serum prolactin level and shrinkage of pituitary adenoma. Described case emphasize the crucial role of identification of hyperprolactinemia among young patients on early stages of the disease. Our observation implies that treatment with dopamine agonists might be effective even in cases with giant prolactinomas.

Background. Insulinoma is the most common functional pancreatic neuroendocrine tumor originating from β-cells, with unregulated insulin production and rarely associated with MEN-I syndrome. Diagnosis and treatment of insulinoma are a challenge in the practice of endocrinologist. Aim. To determine on the basis of retrospective analysis the optimal approaches to the management of patients with organic hyperinsulinism. Material and methods. Medical records of 72 patients admitted with suspected organic hyperinsulinism had been screened and medical histories of patients with a confirmed diagnosis of organic hyperinsulinism were included into the analysis. Anamnesis, results of objective, laboratory and instrumental examinations, methods and results of the treatment were analyzed. Results. The diagnosis of insulinoma was confirmed in thirty two cases. Hypoglycemia was achieved within the first 48 hours after the start of the 72-hour fasting test in 100% of cases. Study results showed that in 50% of cases the size of the pancreatic neoplasm was more than 1.4 cm. Inverse correlation between tumor size and plasma glucose concentration at the time of hypoglycemia was found (r=–0.45; р=0.02). Surgical treatment was carried out in thirty out of 32 patients. Surgical enucleation of insulinoma was performed in 12 (40%) cases, distal pancreatectomy — in 18 (60%). Insulinoma was confirmed in 27 cases, while in three patients diagnosis of non-insulinoma pancreatogenous hypoglycemia («nesidioblastosis») was established according to histological findings. Positive clinical result was achieved after all surgeries. In postoperative period patients were discharged within 11—30 days. Patients without post-operative complications were discharged 13.0±1.4 days after surgery. Twelve (40%) patients developed post-operative complications. The duration of hospital stay in these cases was significantly longer 20.1±1.9 (р

For a long time, surgical removal of somatotropinoma using the transsphenoidal approach has been the first stage of treatment in most acromegaly patients. For the past decades, the efficacy criteria for surgical treatment of acromegaly have significantly changed, which requires appropriate correction.We aimed to evaluate the results of transsphenoidal adenomectomy in acromegaly patients using various criteria for disease remission.The study included patients with newly diagnosed acromegaly who underwent transnasal transsphenoidal endoscopic adenomectomy performed by a single neurosurgeon. The surgical treatment outcomes were evaluated 6 months after operative intervention based on levels of IGF-1, OGTT, and GH. The obtained data were analyzed using different threshold values for the level of GH nadir during OGTT: criteria A2.0 ng/ml, criteria B1.0 ng/ml, and criteria C0.4 ng/ml to assess acromegaly remission, along with matching of the IGF-1 level to the reference range for a given gender and age.The study included 70 patients (52 females and 18 males) with a mean age of 52.2±11.5 years (29 to 73 years). The baseline IGF-1 level exceeded the upper limit of the reference range 3.3±1.4 (1.1-7.3)-fold, on average. The baseline mean basal GH level was 34.2±41.7 (1.2-192.0) ng/ml. The mean pituitary adenoma size was 16.7±8.6 (4.3-46.0) mm; 18 (26%) out of 70 patients had pituitary microadenoma, and 52 (74%) patients had macroadenoma. Six months after surgery, acromegaly remission met criteria A in 47 (67%) patients, criteria B in 28 (40%) patients, and criteria C in 18 (26%) patients.Our findings demonstrate that evaluation of transsphenoidal adenomectomy outcomes in treatment of acromegaly patients depends on the criteria chosen for assessing remission. This feature should be considered when comparing outcomes of surgical treatment for acromegaly in different years. Probably, introduction of the 2010 criteria should be accompanied by revision of the previous remission indicators.Уже давно первым этапом лечения пациентов с акромегалией в подавляющем большинстве случаев является хирургическое удаление соматотропиномы транссфеноидальным доступом. В течение последних десятилетий критерии эффективности хирургического лечения акромегалии значительно изменились, что требует сегодня соответствующей коррекции. Цель исследования - оценить результаты транссфеноидальной аденомэктомии у пациентов с акромегалией с использованием различных критериев ремиссии заболевания. Материал и методы. В исследование включили пациентов с впервые выявленной акромегалией, которым была выполнена трансназальная транссфеноидальная эндоскопическая аденомэктомия одним нейрохирургом. Результаты хирургического лечения оценили через 6 мес после оперативного вмешательства путем определения уровня ИФР-1 и ОГТТ с определением ГР. Полученные данные проанализировали, используя различные пороговые значения уровня ГР в ОГТТ: критерии А2,0 нг/мл, критерии В1,0 нг/мл, критерии С0,4 нг/мл для оценки ремиссии акромегалии наряду с соответствием уровня ИФР-1 референсному диапазону для данного пола и возраста. Результаты. В исследование включены 70 пациентов (52 женщины и 18 мужчин), средний возраст которых составил 52,2±11,5 года (от 29 до 73 лет). Исходный уровень ИФР-1 превышал верхнюю границу референсного диапазона в среднем в 3,3±1,4 (1,1-7,3) раза. Исходно средний базальный уровень ГР составил 34,2±41,7 (1,2-192,0) нг/мл. Размер аденомы гипофиза - 16,7±8,6 (4,3-46,0) мм; 18 (26%) из 70 пациентов имели микроаденому гипофиза, 52 (74%) пациента - макроаденому. Через 6 мес после хирургического лечения критериям А ремиссии акромегалии соответствовали 47 (67%) пациентов, критериям В - 28 (40%) пациентов, критериям С - 18 (26%) пациентов. Выводы. Согласно данным нашего исследования, оценка результатов транссфеноидальной аденомэктомии при лечении больных акромегалией зависит от выбранных критериев оценки ремиссии. Эту особенность следует учитывать при сравнительном анализе результатов хирургического лечения акромегалии в разные годы. Очевидно, что с введением критериев 2010 г. прежние показатели ремиссии требуют пересмотра.

Background: MPOWERED, a large phase 3 trial, assessed maintenance of response to oral octreotide capsules (OOC; MYCAPSSA®) compared to injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly who responded to OOC and iSRLs (octreotide or lanreotide). OOC were recently approved in the US for patients with acromegaly who responded to and tolerated iSRLs. Methods: Eligibility criteria included age 18-75 years at screening, acromegaly diagnosis, disease evidence, biochemical control (insulin-like growth factor I [IGF-I] Results: Of 146 enrolled patients, 92 entered the RCT (OOC, n=55; iSRLs, n=37). Both arms were well balanced for age, sex, and acromegaly duration. OOC demonstrated noninferiority to iSRLs in maintaining biochemical response, with 91% (CI, 80%-97%) of OOC and 100% (CI, 91%-100%) of iSRL groups maintaining control during the RCT. Of those responding at end of Run-in, 96% of patients on OOC maintained response during RCT. Using nonresponse imputation, 89% of OOC and 95% of iSRL groups were biochemically controlled in RCT. Landmark analysis of those respnding at end of Run-in showed that 94% of patients in each group maintained response at RCT end. In both groups, IGF-I levels were stable in the RCT, average IGF-I at baseline and RCT end being 0.9 × ULN (OOC) and 0.8 × ULN (iSRL). Mean change in GH from RCT start to RCT end was -0.03 ng/mL (OOC) and +0.29 ng/mL (iSRL). Safety data were mostly similar between groups; the OOC group did not experience injection site reactions. Conclusion: In this noninferiority trial in patients with acromegaly, OOC demonstrated maintenance of biochemical response compared to iSRLs. Results support the efficacy of OOC as a possible iSRL alternative.

Improved prognoses of patients with type 2 diabetes are primarily determined by the extent of blood glucose control (correction of both hyper- and hypoglycemia and normalization of blood glucose levels). The proper identification and timely correction of abnormal blood glucose levels require frequent blood glucose monitoring by the patient. Currently used methods for the self-monitoring of blood glucose have significant drawbacks that limit their use. The most significant problems with these methods include insufficient accuracy, invasiveness and high cost, leading to noncompliance and difficult assessment of disease status. Such factors underscore the need for a noninvasive, cost-effective and highly accurate method to measure blood glucose levels. There are several different approaches for the noninvasive measurement of blood glucose levels, including optical analysis, ultrasound and bioimpedance. The concept of a noninvasive glucometer was launched more than 30 years ago. Nevertheless, most noninvasive technologies are still in early stages of development and are not used in clinical practice. This review describers the most promising developments in this area.

Introduction: Recent studies have demonstrated that vitamin D deficiency contributes to the development of metabolic disorders, including obesity and type 2 diabetes mellitus (T2DM). Several vitamin D receptor (VDR) gene polymorphisms had been described to play a role in these conditions since vitamin D receptors were found in many tissues. The aim of this study was to assess the relationship between vitamin D status and VDR gene polymorphisms with metabolic syndrome (MS) parameters in Russian middle-aged women.Materials and Methods: A total of 697 women aged between 30 to 55 years were included in this cross-sectional study. Serum 25-hydroxyvitamin D (25(OH)D) level and four VDR gene polymorphisms rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI), and rs2228570 (FokI) were measured. We applied the International Diabetes Federation (IDF) criteria to identify subjects with MS.Results: 9.3% of subjects had normal vitamin D level, while 90.7% were insufficient or deficient. Abdominal obesity (AO) was seen in 75.5%, impaired glucose tolerance (IGT) or T2DM was observed in 33.3%, reduced high-density lipoprotein cholesterol (HDL-C) level in 32.2% and hypertriglyceridemia in 23.4%. Serum 25(OH)D level in women with or without MS did not differ (48.6 ± 1.8 and 51.1 ± 1.5 nmol/l, p > 0.05). Subjects with vitamin D deficiency showed an increased risk of AO [CI 95% 2.23; 1.15–4.30] and low HDL-C [CI95% 2.60; 1.04–6.49] compared to subjects with normal 25(OH)D level. IGT and T2DM risk was increased only when 25(OH)D concentration was less than 39.0 nmol/l [CI 95% 7.17; 2.99–17.7], but risk of MS did not differ in normal vitamin D status subjects and insufficient/deficient ones (p > 0.05). T allele carriers (A) of rs7975232 had higher total cholesterol and low-density lipoprotein cholesterol levels compared with the GG (aa) genotypes. Similarly, GG (BB) genotype carriers of rs1544410 had higher triglyceride levels than subjects with A (b) allele carriers. However VDR gene polymorphisms did not seem to be associated with an increased risk of MS.Conclusions: Vitamin D deficiency, rs7975232, and rs1544410 VDR gene variants are associated with MS parameters in Russian middle-aged women.

Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking. Methods: A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas. Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival. Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities. Funding Statement: Supported in part by the grant AZV 16-32665A to Sarka Dvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng. Declaration of Interests: None of the authors have relevant conflicts of interest. Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.

The detection of a genetic organization of common diseases is one of the first key direction in modern medicine. In thyrotoxicosis, identification of genetic predictors, defining remission and the risk of cardiovascular complications is of a great importance. We gave attention to the second of above mentioned aspects. Candidates for genetic prediction are the genes regulated by triiodothyronine and playing a key role in changing of the myocardial contractility and arrhythmogenesis. There are SNPs of the β1-adrenergic receptor (ADRB1) gene among them: polymorphism in the 389 codon (Gly389Arg) and polymorphism in codon 49 (Ser49Gly). The investigation goal was to determine whether the deleterious effects on cardiovascular system of the thyroid hormones excess in people with thyrothoxicosis were modified by polymorphic variants of ADRB1 gene. So we investigated the possible link of these two SNPs with clinicopathologic findings, echocardiographic parameters and the changes during therapy in 165 patients with a thyrotoxicosis caused by Gravesdisease without any nonthyrotoxic cardiovascular disorders. The data analysis demonstrates that both Gly389Arg and Ser49Gly polymorphisms have very moderate influence on the risk of atrial arrhythmias, left ventricular hypertrophy and its type (concentric or eccentric). Genotype Gly389Gly (Gly389Arg polymorphism) or genotype Gly49Gly (Ser49Gly polymorphism) carriers have tendency to the lowest risk of cardiovascular complications during thyrohoxicosis, but no statistically significant effects were revealed.

To search for the association between vitamin D status and anxiety and depression.Authors examined 310 residents of St. Petersburg (137 men and 173 women). Anxiety and depression were measured with the HADS.In people with vitamin D deficiency, anxiety and depression were noted in 32.5% and 11.0%, respectively. There were negative correlations between serum 25(OH)D level and anxiety (r= -0,11, p=0.03). Symptoms of depression were not correlated with vitamin D status (r= -0.08, p=0.09) but were correlated with the age (r=0.12, p=0.02). After excluding other risk factors for psychogenic disturbances (obesity, hypertension and impaired glucose metabolism) we concluded that serum 25(OH)D could be an independent risk factor for anxiety (R2=0.02, p=0.01) in the population studied.Цель исследования - изучение связи между уровнем обеспеченности витамином D и наличием тревожно-депрессивных расстройств. Материал и методы. Обследовали 310 (137 мужчин и 173 женщины) жителей Санкт-Петербурга. Оценку тревоги и депрессии проводили по шкале HADS. Результаты и заключение. При недостатке витамина D наличие тревожного расстройства было выявлено у 32,5% и депрессивного расстройства - у 11% обследованных. Установлена отрицательная связь между уровнем 25(ОН)D в сыворотке крови и степенью выраженности тревожных нарушений (r= –0,11; p=0,03); степень выраженности депрессивных нарушений коррелировала лишь с возрастом обследованных (r=0,12; p=0,02), но не была связана с уровнем обеспеченности витамином D (r= –0,08; p=0,09). Исключение таких факторов, как ожирение, артериальная гипертензия, нарушение метаболизма глюкозы позволило определить самостоятельный вклад низкого уровня 25(ОН)D в сыворотке крови в развитие тревожного расстройства в исследованной популяции (R2=0,02; p=0,01).

Background. Several previous studies suggest that the drug in the biguanide class — metformin, in addition to the well-known hypoglycemic action can exert a significant cardioprotective effect. Molecular mechanisms of cardioprotection mediated by metformin are practically unknown. Objective. To examine the role of AMP-activated protein kinase (AMPK) — a key regulator of energy metabolism in myocardial tolerance to ischemia and reperfusion injury under the action of metformin in animals with type 2 diabetes mellitus (T2DM). Design and methods. The Wistar rats with streptozotocin-induced neonatal type 2 diabetes mellitus were used in the study. Ischemia-reperfusion of the myocardium was modeled according to Langendorf on the isolated heart with the preliminary intraperitoneal administration of metformin for 3 days. Cardioprotective effect of metformin was assessed by hemodynamic parameters and the size of myocardial infarction. AMPK activity in the myocardium was assessed by Western blot analysis. Results. Metformin did not significantly affected infarct size and nature of the postischemic recovery of left ventricular function in control group and in animals with T2DM. At the same time, the infarct size in T2DM was significantly lower than in the controls, which confirms the phenomenon of metabolic preconditioning. Activation of AMPK in the myocardium compared with the control group was observed in animals with T2DM, and in both metformin groups. Administration of metformin to animals with T2DM was accompanied by the maximum increase in AMPK activity. Conclusions. T2DM led to the activation of AMPK and was accompanied by improved myocardial tolerance to ischemia. In the absence of significant cardioprotective effect pre-ischemic systemic administration of metformin led to the increase of AMPK activity in the myocardium that was the highest in the animals with T2DM and metformin administration.