Functional condition of the thyroid gland of newborns from methers with a diffuse toxic goiter

Objective: to study the functional state of the thyroid gland in newborns from mothers with diffuse toxic goiter, depending on the level of antibodies to thyroid stimulating hormone receptors (AB-rTSH).Materials and methods: 68 newborns from 67 mothers with diffuse toxic goiter were examined. The control group included 49 newborns from 49 mothers without thyroid pathology. To assess the functional state of the thyroid gland of newborns, we determined the levels of thyroid stimulating hormone, free thyroxine (fT4), and AB-rTSH in cord blood and calculated the TSH/fT4 coefficient, which allows us to differentiate congenital hypothyroidism from neonatal thyrotoxicosis. On the 4-7th day of life, all newborns underwent ultrasound examination (ultrasound) of the thyroid gland.Results: newborns from mothers with diffuse toxic goiter had lower growth-weight indices in comparison with the same indices of the control group and they often showed thyroid hyperplasia. It was shown that the increased content of AB-rTSH in the blood serum of pregnant women with diffuse toxic goiter and in the umbilical cord blood of newborns can contribute to the development of neonatal thyrotoxicosis, detected in 16.2 % of newborns.Conclusions: increased levels of AB-rTSH in the blood serum of mothers with DTG, especially in the second half of pregnancy, and in the umbilical cord blood of newborns affect the formation of thyroid hyperplasia in newborns and contribute to the development of neonatal thyrotoxicosis

Clinical effect of thiazolidinediones in subjects with disorders of carbohydrate metabolism in case of polymorphism rs1801282

BACKGROUND: The polymorphism rs1801282 (Pro12Ala) may be one of the reasons for the heterogeneous response of patients with carbohydrate metabolism disorders to thiazolidinedione therapy. Studies of this polymorphism in patients with metabolic syndrome (MS) will help identify a group of patients in whom the use of thiazolidinedione is advisable. AIMS: To assess the clinical effect of thiazolidinediones in patients with metabolic syndrome, depending on the presence of polymorphism rs1801282. MATERIALS AND METHODS: All patients with newly diagnosed MS with impaired carbohydrate metabolism were included in the open cohort study. All patients were recommended a diet, expansion of physical activity and pioglitazone at a dose of 30 mg per day. After the appointment of the therapy, the patients come to the center back at 12 weeks. The main outcome in the study assessed in patients with impaired glucose tolerance (IGT) was fasting glycemia and 2 hours after glucose tolerance test, in patients with type 2 diabetes — HbA1c. RESULTS: 109 patients were included in the study. Of these, 14 were carriers of rs1801282, the other 95 had a typical PPARγ genotype. After the appointment of therapy in the groups of IGT and type 2 diabetes, improvement of glycemic control was observed. The degree of decrease in fasting plasma glucose and after glucose tolerance test was more pronounced with IGT in patients with polymorphism rs1801282 compared with the rest (plasma fasting plasma glucose level was -0.7 [-0.9, -0.7] vs. -0, 4 [-0.5, -0.3] mmol/L, p=0.001; plasma glucose level 2 hours after glucose tolerance test was -1.1 [-1.8, -0.3] vs. -0.5 [-0.7, -0.1] mmol/L, p=0.031). In patients with type 2 diabetes, no data were obtained for the statistically significant effect of rs1801282 polymorphism on the results of pioglitazone, but there was a tendency for a greater decrease in fasting plasma glucose in the case of carrying the polymorphic gene (-1.9 [-2.2, -1.8] against -1,5 [-1,7, -1,2] mmol/l, p=0,073). CONCLUSIONS: The study shows the effect of polymorphism rs1801282 on the results of pioglitazone in patients with MS, both in IGT and in type 2 diabetes. Carrying polymorphism leads to a significant decrease in fasting glycemia and after glucose tolerance test in patients with IGT. The tendency to improve the parameters of carbohydrate metabolism (fasting glycemia, HbA1c) was noted in a subgroup of patients with type 2 diabetes

The role of high performance liquid chromatography in the functional state of the adrenal glands before and after surgical treatment for corticosteroma

Objective: It is to evaluate the functional state of the adrenal cortex after surgical treatment in patients with corticosteromas for optimize of tactic of postoperative management.Materials and methods: We examined 143 patients (43 men and 100 women) aged 51.3 ± 10.1 years with incidentaloma of adrenal glands and 27 healthy peopels (control group) aged 45.5 ± 5.7 years. Cushing's syndrome was detected in 22 patients, autonomous cortisol secretion was detected in 43. All patients had an analysis of the complaints, objective, laboratory and instrumental data in the preoperative and early postoperative periods. Assessment of levels glucocorticoid and mineralocorticoid hormones in biological fluids was carried out by immunoassay and high performance liquid chromatography.Results: The signs of adrenal cortex insufficiency in the early postoperative period were obtained in 77.3% of patients with Cushing's syndrome and in 25% of patients with autonomous cortisol secretion according to immunoassay and high performance liquid chromatography. An increase of level of corticosterone in the serum of blood in the preoperative period indicate the possibility development of adrenal insufficiency in the early postoperative period in all patients. Аn increase of levels of 11-deoxycortisol and 18-OH-corticosteronein in the serum of blood аnd urinary excretion of free cortisone, 18-OH-corticosterone and 6β-hydroxycortisol indicate the possibility development of adrenal insufficiency in the early postoperative period in patients with Cushing's syndrome.Conclusions: The determination of cortisol and aldosterone precursors by high performance liquid chromatography increases the accuracy of the diagnosis of glucocorticoid and mineralocorticoid function of the adrenal cortex in patients with Cushing's syndrome and with autonomous cortisol secretion in the early postoperative period

Promising developments in the fi eld of diff erential diagnosis of benign and malignant thyroid nodules

In recent years, the ability to determine the nature of thyroid nodules has been signifi cantly improved both through the improvement of traditional methods, such as ultrasound examination (ultrasound) and fi ne needle aspiration biopsy (TAB), and through the creation of fundamentally new approaches. Th e review contains the most relevant achievements of recent years. Th e literature search was carried out in the bibliographic base of the Russian Science Citation Index for the words «node», «thyroid gland», «diagnosis», «cancer» on the site «https://www.elibrary.ru», as well as in the database of medical and Biological publications of the US National Center for Biotechnology Information on «nodule», «thyroid», «diagnostics», «cancer» at https://pubmed.ncbi.nlm.nih.gov. Th e analysis of sources for the last 5 years has been carried out

Pharmacogenetic aspects of vildagliptin treatment in patients with newly diagnosed type 2 diabetes mellitus

Objective: to study a role of the rs5219 polymorphism in KCNJ11 in the formation of the response variability to vildagliptin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Materials and methods: 48 patients with newly diagnosed T2DM were examined. For all patients vildagliptin in a dose of 50 mg/day was prescribed. If necessary, dose titration was carried out or other glucose-lowering therapy was prescribed for 6 months of observation. Dynamics of the main indicators of glycemic control and body mass index were studied, presence of the rs5219 polymorphism in KCNJ11 gene was also determined.Results: all patients-carriers the T allele had achieved the target values of glycated hemoglobin (HbA1c) in 3 months of vildagliptin monotherapy, compared to patients with wild-type gene who achieved target values of HbA1c in only 44,4% of cases. Increasing the dose to 100 mg/day required 35% of patients with wild-type gene and 17.9% of patients with rs5219 polymorphism. The appointment of a combination of glucose-lowering therapy was necessary in 40% of patients with the wild-type gene and no one with polymorphism.Conclusion: the presence of the polymorphic allele T rs5219 in KCNJ11 gene makes it possible to predict the high efficacy of vildagliptin monotherapy in patients with newly diagnosed T2DM

Draft of Russian Clinical Practice Guidelines «Male hypogonadism»

Hypogonadism in males, defined as a decrease in serum testosterone levels in combination with characteristic symptoms and/or signs, can be observed with pathological changes in the testicles and/or pituitary gland, such as Klinefelter’s syndrome, Kallman’s syndrome, as well as in men with metabolic (obesity, diabetes mellitus) or iatrogenic disorders leading to a decrease in androgen production. The draft guidelines cover the extensive range of pathologies that cause hypogonadism development (testosterone deficiency) and focus on its clinical variants, which make up the majority of cases of hypogonadism observed in men. The authors and reviewers are an interdisciplinary group of experts, consisting of endocrinologists, andrologists, urologists - members of the «Russian Association of Endocrinologists» and «Men’s and Reproductive Health» public organizations.Clinical guidelines contain the most reliable evidence available to experts at the time of writing. Nevertheless, recommendations cannot replace clinical experience, and deciding on the start of treatment, choosing a method of therapy, or a drug should always consider the individual characteristics of a specific patient

Prevalence of hypoglycemic conditions in adolescents with type 1 diabetes mellitus in real clinical practice

BACKGROUND. Hypoglycemia and fear of hypoglycemia remain critical problems in the treatment of adolescents with type 1 diabetes mellitus (DM1) and are factors limiting proper control of glycemia and preventing the achievement of metabolic compensation of the disease. The use of pump insulin therapy involves the prevention of hypoglycemic conditions.AIM. To analyze the frequency and duration of hypoglycemia episodes, their effect on the metabolic compensation of the disease in adolescents with type 1 diabetes mellitus (DM1) in real clinical practice, depending on the mode/method of insulin administration.MATERIALS AND METHODS. The study involved 117 adolescents with DM1 aged 12 to 19 years (average age 15.5 years). 37 adolescents received therapy by continuous subcutaneous insulin infusion (CSII); 80 adolescents received therapy by multiple insulin injections (MII). The level of glycated hemoglobin (HbA1c) was determined for all adolescents, and its main indicators were evaluated using a 6 days continuous glucose monitoring (CGM) by the «blind» method of a professional system with an iPro 2 sensor (Medtronic MiniMed, USA).RESULTS. Episodes of a decrease in glucose levels <3,9 mmol/l were recorded in 87% of patients (n=102), 63% (n=74) showed a decrease in glucose levels <3,0 mmol/l. Episodes decrease in glucose levels <3,9 mmol/l at night were recorded in 68% of patients (n=80), and with glucose levels <3,9 mmol/l in 46% (n=54). The frequency of episodes of glucose lowering <3,9 mmol/l had no statistically significant differences depending on the methods of insulin administration (by continuous subcutaneous insulin infusion or multiple insulin injections), however, they are more common in adolescents with HbA1c <7,0% (p=0,03). The median time spent by patients in the range of <3,9 mmol/l was 5% per day, and a longer time in this range was observed in patients with HbA1c <7,0% (p=0,006). The median time in the range of <3,0 mmol/l was 1% per day and had no significant differences depending on the level of HbA1c (p=0,559). There were also no significant differences depending on the groups using CSII and MII (p=0,640 and p=0,250).CONCLUSION. Episodes of glucose reduction in the range of <3,9 mmol/l according to CGM data are more common in adolescents with HbA1c target values, regardless of the method of insulin administration. Significantly more time in range of <3,9 mmol/l is spent by adolescents with target values of HbA1c i.е. <7,0% compared with HbA1c ≥7,0%, however, in both groups, a large number of patients had time in the range below the target level was higher than recommended values

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049