Vol 27, No 12 (2020)

In recent years, the prevalence of both benign and malignant tumors of the thyroid gland has increased, mainly among women of working age. Despite numerous studies devoted to the evaluation of the mechanisms of the development of thyroid tumors, many questions remain unresolved, and it does not allow effective implementation of their primary prevention and reduce the risk of recurrence. This review considers modern views on the mechanisms of oncogenesis in the thyroid gland, presents data on the role of imbalance of trace elements, insulin resistance, growth factors, disorders in the state of the immune system and antioxidant protection in the formation of thyroid tumors. Probably, these data will provide a new approach to the diagnosis and prevention of thyroid tumors.

The world has already accumulated extensive experience in the use of continuous glycemic monitoring using the FreeStyle Libre Flash monitoring system in patients with diabetes mellitus. The article presents an analysis of recent publications on this issue. Based on the data analyzed, it can be argued that the use of the FreeStyle Libre Flash monitoring system in patients with DM1 and DM2 on insulin therapy can lead to a decrease in the level of glycated hemoglobin and glycemic variability, a significant decrease in the number and duration of hypoglycemic episodes, the risk of developing ketoacidosis, and an improvement in quality of life indicators.

Background. Oral antidiabetic drugs (OADs) are the mainstay of drug therapy for type 2 diabetes mellitus (DM2), their choice depends on the dominant clinical problem and individual goals. However, despite the significant replenishment of doctors’ arsenal with modern drugs, not all patients manage to achieve optimal glycemic control and maintain it for a long time. If the OADs are ineffective, treatment is supplemented with insulin administration. One of the possible methods of achieving the individual goal of DM2 therapy is the use of the drug Subetta. Objective. Evaluation of the efficacy and safety of Subetta for patients without optimal control of DM2 during treatment with basal insulin in combination with metformin and/or sulfonylurea medication. Methods. A multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in 17 medical centers in the Russian Federation. The effectiveness of therapy was analyzed on the basis of data from 140 randomized patients in whom glycated hemoglobin (HbA1c) level remained within 7.0-10.0% during complex therapy (basal insulin ≥10 U/day+metformin and/or sulfonylurea medication) for ≥3 months prior to study enrollment. Patients in the Subetta group (n=73), in addition to complex therapy, received the tested drug, 1 tablet 4 times a day for 36 weeks, patients in the placebo group (n=67) - complex therapy plus placebo according to the Subetta regimen. The primary endpoint was the change in mean HbA1c level at 12, 24 and 36 weeks of treatment from baseline. The dynamics of fasting plasma glucose (FPG) level, indicators of the 7-point self-monitoring of blood glucose (SMBG) profile, daily doses of insulin and OADs, body weight and body mass index (BMI) during 36 weeks of treatment were assessed as secondary endpoints. Results. Patients in both groups did not differ in demographic, anthropometric and baseline clinical characteristics. According to Intention-to-Treat analysis, the mean decrease in HbA1 level in patients of the Subetta group after 12, 24 and 36 weeks of treatment was -0.53±1.06%, -0.54±1.00% and -0.54±1.11%, which was significantly different compared to the placebo group (-0.01±1.06%, -0.07±1.19% and +0.15±1.07%; p=0.0096, p=0.0107 and p=0.0009, respectively). The target HbA1c values at 36 weeks were reached by 19.2% of patients in the Subetta group (versus 4.5% in the placebo group; p=0.009). The results of the per protocol analysis showed an even more significant decrease in HbA1c level compared with placebo therapy: -0.70±1.04%, -0.65±1.04% and -0.70±1.13% versus +0.03±1.09%, -0.07±1.21%, and +0.15±1.07% (p=0.0006, p=0.0056 and p=0.0003, respectively). FPG level after 4 weeks of Subetta’s use decreased by -0.5±2.6 mmol/L (versus -0.1±3.2 mmol/L in the placebo group; p=0.3362) and remained at a stable level in the next 24 weeks. In the placebo group, the FPG level, on the contrary, increased: +0.9±4.1 mmol/L after 24 weeks (p=0.2778) and + 1.0±3.7 mmol/L after 36 weeks (p=0.2778). After 36 weeks of treatment with Subetta, there was a tendency towards a decrease in postprandial glycemia (according to the 7-point SMBG profile), basal insulin doses (-0.9±2.4 IU/day versus +3.5±9.5 IU/day in placebo group; p=0.0605) and BMI (-0.04±0.78 kg/m2 versus +0.14±1.33 kg/m2 in the placebo group; p=0.3410). There were 2 episodes of symptomatic daytime hypoglycemia in the Subetta group and 8 in the placebo group. No cases of evere hypoglycemia were identified. Subetta did not adversely affect the vital signs of the study participants. A total of 49 adverse events (AEs) were noted in 23 (30.3%) patients in the Subetta group and 39 AEs in 25 (34.7%) participants in the placebo group. The number of patients with AEs, as well as AEs related to one or another MedDRA code (Medical Dictionary of Regulatory Activity Terminology), did not differ between the two groups (p=0.60). The distribution of AEs depending on the severity (p=0.419) and the reliability of the causal relationship with the drug (p=0.166) did not differ between two groups. No AEs were reported that were reliably associated with the tested drug. Biochemical blood test, general clinical blood and urine tests did not reveal clinically significant deviations and differences in both groups after 12, 24 and 36 weeks of treatment. Compliance rates were close to 100% in the two groups. Conclusion. The combination of Subetta with basal insulin and OADs (metformin and/or sulfonylurea medication) is a rational combination for DM2. In patients without control of DM2 against the background of basal insulin and OAds for ≥3 months, the inclusion of Subetta leads to a significant optimization of glycemic control. The HbA1c level achieved in 12 weeks remains stable over the next 24 weeks of treatment. The therapeutic efficacy of the drug is combined with a good safety profile and a high level of patient adherence to therapy.

Background. In order to choose the optimal treatment tactics for patients with adrenal incidentaloma (AI), the borderline values of hormonal parameters in doubtful situations require evaluation of the steroid metabolome using chromatographic methods, among which gas chromatography-mass spectrometry (GC-MS) of urine steroids is the most informative. Objective. Evaluation of the characteristics of steroid metabolism in patients with AI using metabolome analysis based on gas chromatography-mass spectrometry. Methods. Steroid urine profiles were studied by GC-MS on a SHIMADZU GCMS-QP2020 gas chromatography-mass spectrometer using liquid extraction. The functional state of the pituitary-adrenal cortex system was assessed by the immunochemiluminescent method. Results. 205 patients with AI were examined. In 29 patients with autonomous cortisol secretion of (ACS) its level after a test with 1 mg of dexamethasone was more than 140 nmol/L and in 35 patients with possible ACS (pACS) cortisol level of after a test with 1 mg of dexamethasone was less than 140 nmol/L. General chromatographic signs of a decrease in androgenic and an increase in glucocorticoid functions of the adrenal cortex, which were higher in patients with ACS, were obtained. Among 141 patients with normal results of test with 1 mg of dexamethasone, 15 (10.6%) patients showed chromatographic signs of 21-hydroxylase deficiency, 83 (58.9%) showed an increase in androgenic and mineralocorticoid functions of the adrenal glands, a positive correlation of androgens and their metabolites with a malignant potential, which must be taken into account when deciding on surgical treatment. Conclusion. Signs of decreased activity of type 2 11β-hydroxysteroid dehydrogenase and 11β-hydroxylase were common abnormalities in steroid metabolism in patients with ACS and pACS. In patients with ACS, an increase in the activity of 5β-reductase was observed; urinary excretion of tetrahydrometabolites of cortisol, cortisone, corticosterone, and 11-deoxycortisol was higher than in patients with pACS. In patients with AI with cortisol levels less than 50 nmol / L after a test with 1 mg of dexamethasone, signs of 21-hydroxylase deficiency (10.6%), an increase in androgenic and mineralocorticoid functions of the adrenal cortex, and 11β-hydroxylase and 17-hydroxylase deficiency were observed in 58.9% of patients.

Background. Type 2 diabetes mellitus (DM2) is one of the aggravating factors of ENT pathology. Currently, the algorithms for the complex treatment of pyoinflammatory diseases of the ENT organs do not include the appointment of immunocorrecting therapy, although it has been proven that immune changes play an important role in the pathogenesis of both ENT diseases and diabetes mellitus. Sodium deoxyribonucleate (SDN) and azoximer bromide (AB) are the drugs that have proven clinical efficacy in the treatment of purulent ENT diseases. Objective. Comparative analysis of the effectiveness of therapy with SDN and AB in patients with rhinosinusitis and otitis media against the background of DM2. Methods. An immunological study was carried out in 25 DM2 patients with rhinosinusitis and otitis media aged from 35 to 70 years. The mean age of the patients was 52.9±8.34 years. The first group included 13 patients receiving SDN, the second - 12 patients receiving AB. The immunoglobulin (Ig) A., M, G and E, interleukin (IL) -4 and -18 levels were determined in all patients. Results. After treatment with SDN, a significant decrease in the IL-4 and -18 levels was observed, while using AB, a significant increase in IgA and IL-18 was detected. The clinical efficacy of therapy with SDN was 81%, while the glucose level decreased from 11.10 to 6.0 mmol/L (p=0.0015). After the treatment with AB, the clinical efficacy was 83%, the glucose level decreased from 10.9 to 7.3 mmol/L (p=0.0022). Conclusion. SDN and AB do not significantly differ in clinical efficacy for patients with rhinosinusitis and otitis media. At the same time, against the background of the use of SDN, there was a decrease in the IL-4 and -18 levels, and during therapy with AB, an increase in the IgA and IL-18 levels was noted, which reflects the immunocorrecting direction of the action of the studied drugs.

Results. Treatment that included β-AB in both groups showed comparable effects on blood pressure, heart rate, and anginal syndrome. During the follow-up in group A., compared with group B, the decrease in body mass index (by 6.6 and 1.45%), HbA1с (by 12.1 and 7.8%), the HOMA-IR index (by 29.2 and 18.8%), as well as the levels of total cholesterol, LDL cholesterol, blood triglycerides, and proteinuria were statistically significant, all p<0.05. Beneficial metabolic effects of treatment included vasodilating β-AB did not depend on the gender of patients, their age, initial values of HbA1c and lipid parameters, features of myocardial infarction, the presence and stage of arterial hypertension, heart failure, diabetic nephropathy, and the choice of a specific vasodilating β-AB (all p>0.05). Side effects of β-AB were observed in 16 (23.9%) cases (7 in group A and 9 in group B). No drug withdrawal was required in any of the cases. Conclusions. 1. Treatment with different β-AB was satisfactorily tolerated in post-myocardial infarction patients with DM2. Treatment with vasodilating and non-vasodilating β-AB, prescribed in addition to standard therapy, resulted in comparable hypotensive and antianginal effects, as well as a similar degree of heart rate reduction. In the group of patients who received vasodilating ß-AB, more pronounced beneficial effects of treatment were noted, including a more significant decrease in HbA1c, HOMA-IR index, total cholesterol, LDL cholesterol, triglycerides and proteinuria. Taking into account the better metabolic tolerability of vasodilating β-AB carvedilol and nebivolol, these β-AB agents may be preferred for patients with DM2 who have indication for β-AB use based on current recommendations.

On June 19, 2020, an expert panel meeting under the chairmanship of Dr.Sci.(Med.), Professor M.B. Antsiferov was held in Moscow; it was dedicated to the discussion of the latest results of clinical trials of the use of the combined preparation insulin degludec+liraglutide, IDegLira (Sultofay® FlexTouch®) for the treatment of patients with diabetes mellitus (DM) of various groups. The aim of the meeting was to determine the role and place of the drug insulin degludec+liraglutide, IDegLira (Sultofay® FlexTouch®) in the DM2 treatment in real clinical practice based on its benefits confirmed in clinical trials. Thus, the combined drug IDegLira is an effective antihyperglycemic drug that affects different links in the DM2 pathogenesis and makes it possible to personalize DM2 therapy, taking into account the existing complications and concomitant diseases.

Background. The last 20 years of the development of diabetology have been marked by the emergence of many new pharmacotherapeutio options for the management of type 2 diabetes. One promising and effective therapeutic approach is a fixed ratio combination of basal insulin and a GLP-1 receptor agonist. Since 2018, fixed ratio combination of basal insulin glargine 100 U/ml and prandial GLP-1 RA lixisenatide has been available in Russia. As shown by the LixiLan-O clinical study, as well as its subanalysis in patients with a baseline HbA1c level of more than 9%, a fixed combination of insulin glargine and lixisenatide allows 74% of patients who have not previously achieved treatment goals with the use of oral antihyperglycemic drugs to achieve HbA1c less than 7%. Description of the clinical case. This publication presents two clinical cases of successful initiation of insulin therapy with a fixed ratio combination of glargine and lixisenatide in patients with type 2 diabetes with a baseline HbA1c level above 9% who did not reach the target glycemic values when using a combination of oral antihyperglycemic drugs. Conclusion. Comparison and analysis of published data from randomized trials and case studies in real-life clinical practice is essential. The efficacy and safety parameters of the fixed ratio combination of insulin glargine and lixisenatide observed in the cases reviewed correlate with those shown in the LixiLan-O randomized clinical trial.