Vol 29, No 11/12 (2022)

Hypothyroidism is one of the most common diseases of the endocrine system. The nonspecificity of symptoms of hypothyroidism often leads to delayed diagnosis of this disease. The need for screening determination of thyroid-stimulating hormone (TSH) for early detection of hypothyroidism and initiation of its therapy continues to be actively discussed. The article discusses the role of untimely diagnosed hypothyroidism as a factor aggravating the course and compensation of concomitant pathology. At the moment, the determination of the TSH level is indicated for all patients with dyslipidemia, diabetes mellitus, and reproductive disorders. However, it is also advisable to screen for hypothyroidism in people over 40 years of age with metabolic syndrome and vascular risk factors, poorly controlled arterial hypertension, chronic kidney disease, and hematological diseases. Particular attention should be paid to patients with high comorbidity. Early diagnosis of hypothyroidism and timely prescription of replacement therapy can improve the course and compensation of concomitant pathology, reduce the need for its drug therapy, providing the adherence to treatment and improvement of further prognosis for the patient.

Kidney stone disease (KSD) is a significant pathology in clinical practice. One of the most important causes of stone formation are drugs. Drugs lead to drug-induced (DI) KSD by crystallization in the urine and influence on various metabolic processes. Among the drugs capable of crystallization, it is necessary to note antibacterial drugs. KSD inducers from this group include aminopenicillins, quinolones and ceftriaxone. The most important risk factor for nephrolithiasis while taking antibacterial drugs is their use in high doses. In addition to drugs that crystallize in the urine, drugs that affect various metabolic processes play an important role as inducers of KSD. These include calcium supplements, vitamin D and C supplements, and carbonic anhydrase inhibitors. The role of the mentioned additives as inducers of urolithiasis can be underestimated due to their widespread use, including without a doctor’s prescription. Pediatric practice also describes the processes of stone formation against the background of the use of furosemide. It is also necessary to note allopurinol, the mechanism of lithogenesis against the background of which is mixed. The uniqueness of this review is that data on inducer drugs were combined from various sources and structured according to a single plan.

Background. The efficacy and safety of the fixed combination of insulin glargine 100 U/ml and lixisenatide for the treatment of patients with type 2 diabetes mellitus (DM2) have been demonstrated in a number of randomized clinical trials, including the SOLO study, a retrospective cohort study conducted on the territory of the Russian Federation (Moscow). Objective. Evaluation of the efficacy and safety of the fixed combination of glargine 100 and lixisenatide in certain categories of diabetic patients who participated in the SOLO retrospective cohort study, depending on the age of the patients and the initial glycated hemoglobin (HbA1c) level. Methods. SOLO was a retrospective cohort study that included 383 adult DM2 patients with HbA1c levels /7% before starting iGlarLixi, with available retrospective medical information for the period 6 months before the start of therapy with iGlarLixi and 6-12 months after. In this study, the analysis was carried out in groups of patients with different HbA1c levels before use of iGlarLixi (7-<8%, 8-<9%, /9%) and different age groups (<65 and /65 years). Results. The use of iGlarLixi in all analyzed subgroups of patients (with different HbA1c levels and aged <65 and /65 years) led to a decrease in fasting plasma glucose (FPG) and HbA1c after 6 and 12 months. After 12 months, the decrease in HbA1c levels was -0.86%, -1.33 and-2.26%, FPG -1.52mmol/L, -1.95 and -3.09 mmol/L in groups with baseline HbA1c 7<8%, 8<9%, /9%, respectively. After 12 months, the decrease in HbA1c in the group of patients <65 years was -1.76%, in the group /65 years - 1.68%; decrease in FPG -2.4, -2.68 mmol/l, respectively. In all analyzed cohorts of patients, a statistically significant decrease in body weight from baseline values was noted. The use of iGlarLixi was accompanied by a low risk of any hypoglycemia, incl. severe ones. Conclusion. In real outpatient practice, the use of a fixed combination of glargine 100 U/ml and lixisenatide in DM2 patients in groups with different HbA1c levels and age (<65 and /65 years) led to an improvement in glycemic control without increasing body weight and the number of hypoglycemic conditions.

Background. Acromegaly is a severe chronic disease caused by hyperproduction of somatotropic hormone (GH), which significantly affects the quality and duration of life. Growth hormone hyperproduction leads to the development of severe comorbid diseases, including deformation of the axial skeleton, osteoarthritis, cardiovascular diseases, carbohydrate metabolism disorders, and some types of cancer. Compared to the general population, in patients with active acromegaly, early disability and an increase in mortality are noted. Objective. Estimation of the time of the last visit to the expert center for patients with acromegaly in the Moscow region, as well as the proportion of patients with controlled and uncontrolled acromegaly at the time of the last visit, and analysis of the types of treatment performed. Methods. A retrospective observational study was conducted. According to the data of the M.F. Vladimirsky Moscow Regional Research Clinical Institute, there are 377 patients with acromegaly in the Moscow region. For the analysis, medical records of 327 patients with acromegaly observed in the M.F. Vladimirsky Moscow Regional Research Clinical Institute were selected. Controlled acromegaly was defined as a condition with the growth hormone level <2.5 ng/ml, and the insulin-like growth factor 1 (IGF-1) level within the age and gender reference range (except for patients receiving pegvisomant, in such cases only IGF- 1 level was taken into account). Results. The mean age of patients at the time of diagnosis was 49±14.1 years. The majority (52%) of patients were diagnosed between the ages of 41 and 60 years. The number of women (252 patients, 77%) was significantly higher compared to the number of men (75 patients, 23%). At the last visit, the mean age of the patients was 58±13.4 years; 171 (52.3%) patients had controlled acromegaly, 155 (47.4%) patients had uncontrolled acromegaly, and 1 (0.3%) patient had no evidence of acromegaly control at the last visit. In general, 56.6% of patients received neurosurgical treatment, 65.7% of patients received drug treatment, 27.5% of patients received somatostatin analogues as the first line of treatment, and 18.7% of patients received radiation treatment. The analysis made it possible to reveal that 50.8% of patients have not visited the endocrinologist of the CDC of the M.F. Vladimirsky Moscow Regional Research Clinical Institute since 2019 (inclusive). At the same time, half of them (50.6%) were without control of the underlying disease at the time of the last visit. Conclusions. It is recommended to consider the use of neurosurgical intervention in patients with acromegaly in all possible cases, especially if the disease remains active during therapy with somatostatin analogues at maximum dosages. Taking into account, in general, the accumulated experience of many years of use and the favorable efficacy/safety profile of somatostatin analogues, it is advisable to start drug therapy in individuals without achieving the target hormonal criteria for controlling acromegaly either immediately with high dosages, or by rapidly increasing the dose to the maximum possible.

Background. Dipeptidyl peptidase-4 (DPP-4) inhibitors are generally an effective and safe class of antidiabetic drugs for the treatment of type 2 diabetes mellitus (DM2). To date, a series of large randomized controlled trials (RCTs) has been conducted on the cardiovascular safety of the use of DPP-4 inhibitors. Objective. Evaluation of the effect of DPP-4 inhibitors on the risk of cardiovascular events in subgroups of patients with different renal function, as well as among patients who received drugs of this class in addition to metformin. Methods. RCTs were searched in the National Institutes of Health PubMed database for key words as of 12/09/2021. Outcomes assessed included the MACE composite endpoint, death from cardiovascular causes, non-fatal acute myocardial infarction, and non-fatal stroke. Results. In DM2 patients with a high risk of MACE and preserved kidney function, therapy with DPP-4 inhibitor (alogliptin) was associated with a reduced risk ratio for the development of tripartite (RR=0.81; 95% CI: 0.65-0.99) and quadruple (RR=0, 82; 95% CI: 0.650.99) MACE and death from cardiovascular causes (RR=0.61; 95% CI: 0.41-0.92). The addition of alogliptin to metformin compared with metformin alone resulted in a reduced risk of MACE, as well as death from cardiovascular causes and death from all causes. In most studies, DPP-4 inhibitors did not affect the risks of cardiovascular outcomes. Conclusion. DPP-4 inhibitors did not increase the risk of developing cardiovascular events in DM2 patients, and some representatives may have a potential protective effect on the risks of developing certain cardiovascular events in patients with normal kidney function or early stages of chronic kidney disease (glomerular filtration rate> 60 ml/min/1.73 m2) and normoalbuminuria, as well as when used in combination with metformin.

The article discusses modern approaches to the treatment of patients with type 2 diabetes mellitus (DM2) using non-pharmaco-logical and medicinal methods of treatment. The problem of treating diabetes in the modern world does not lose its relevance. Recommendations for the initiation and intensification of therapy for DM2 patients are updated annually. The main stages of the use of hypoglycemic drugs are presented.

Description of the clinical case. A description of the three-phase course of CDI that developed in a child after neurosurgical removal of a giant endosuprasellar craniopharyngioma is presented. Determining the phase of the process was based on indicators of water balance, blood serum electrolytes and osmolality, urine osmolality. During the first and third phases, normo- and hypernatremia (140-153 mmol/l) with simultaneous polyuria and polydipsia was noted; the second phase was characterized by hyponatremia (132-134 mmol/l), high-normal urine osmolality (790-1190 mOsm/kg), oliguria and lack of thirst. During the first and third phases, substitution therapy with desmopressin preparations was carried out with a free drinking regimen. During the second phase, fluid intake was sharply limited in combination with dietary salt supplementation (3-5 g/day) and desmopressin withdrawal. Conclusion. The course of diabetes insipidus after neurosurgical removal of the CSR tumor requires careful monitoring in the postoperative period. Timely detection of the three-phase course of CND and a differentiated approach to the tactics of managing a child in each of the phases make it possible to avoid significant excursion in the blood electrolyte levels up to the development of life-threatening conditions.

Hormone-dependent (ER/PR-positive), human epidermal growth factor 2 receptor-negative (HR+/HER2 negative) breast cancer (BC) accounts for more than 70% of all BC cases. Significant progress in the treatment of HR+/HER2-negative metastatic breast cancer (mBC) has been made, in particular, more adapted and targeted treatments have been developed. Recently, a better understanding of the role of the PI3K/AKT/mTOR signaling pathway in BC has led to the development of PI3K inhibitors that have proven effective in the treatment of HR+/HER2-negative mBC. The role of the PI3K/AKT/mTOR pathogenetic pathway in BC and treatment methods aimed at PI3K inhibition were studied. The development of the PI3K inhibitor alpelisib, indications for its use in HR+/HER2-negative mBC has been completed, safety and tolerability as well as the future direction of this therapy in the treatment of breast cancer are being discussed.

Endocrine therapy for 5-10 years is the standard treatment for women with ER-positive breast cancer (BC). Despite ongoing endocrine therapy, approximately 30% of patients with breast cancer will have a relapse of the disease within 15 years after treatment, indicating a wide variability in the clinical response to tamoxifen treatment. The pharmacological response of tamoxifen may be affected by varying degrees of activity of cytochrome P-450 (CYP) enzymes and P-glycoprotein (Pg) transporters, due to the mass of polymorphisms in the genes of these enzymes. The article presents the results of a prospective pharmacogenetic cohort study analyzing the clinical manifestations of complications of endocrine therapy with tamoxifen in adjuvant mode with assessment of the relationship between the carriage of genetic polymorphisms of genes encoding enzymes of the cytochrome P-450 system and proteins - drug transporters, with the development of adverse events in BC patients. The study involved 120 women with breast cancer who underwent genetic testing for polymorphisms of the CYP and Pg enzyme genes. As a result of associative analysis, their relationship with the development of adverse drug reactions to tamoxifen was shown, indicating the clinical significance of various CYP2D6, CYP3A5, CYP2C9 and ABCB1genetic polymorphisms. Thus, models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to tamoxifen. It is necessary to develop specific clinical guidelines for conducting complex pharmacogenomic testing, which would help to expand our knowledge for the development of more effective and optimal methods of anti-relapse treatment of breast cancer survivors.

Objective. Determination of immune response checkpoints and evaluation of the efficacy of immune checkpoint inhibitors in the treatment of patients with lung cancer. Methods. The study included 34 patients (mean age 63.14±3.16 years) with lung cancer and receiving systemic therapy (including surgical treatment): 27 men (mean age 63.63±3.18 years) and 7 women (mean age 61.29±3.09 years). All patients from the moment of inclusion in the study received immunotherapy: PD-1 blocker - nivolumab/pembrolizumab. During the treatment, no clinically significant side effects were noted, the therapy was tolerated satisfactorily. The results of treatment against the background of immunotherapy were evaluated three times during the period of taking the drugs with the analysis of data from a general blood test, a general urinalysis, a biochemical blood test, thoracic computed tomography and immune checkpoints (PD-1, PDL-1, B7-H3, sHLA, CD314-1, sULPB). Results. In 12 patients (35.29% of cases) stabilization of the pathological process was revealed. The progression of the underlying disease during therapy was recorded in 14 patients: 11 men (40.74% of cases: stage IV of the disease) and 3 women (42.86% of cases: stage IV of the disease). Progression of the underlying disease during therapy was observed in 14 patients, including 11 men (40,74% of cases: stage IV of the disease) and in 3 women (42,86% of cases: stage IV of the disease). Significantly more patients, both women and men, were alive at the time of completion of the study. There was a pronounced downward trend in the checkpoints indicators B7-H3 and sULPB, an increase in CD314-1, sHLA, PDL-1. Conclusions. The obtained results indicate the achievement of stabilization of the malignant process in 35.3% of cases in patients with lung cancer on the background of therapy with immune checkpoint inhibitors as part of complex treatment, and create prerequisites for further studies to evaluate them in terms of improving the prognosis of the disease and life.

Glioblastoma is a recurrent malignant brain tumor. The life expectancy of such patients remains extremely low. Most patients have a tumor recurrence during the first year after its diagnosis, despite ongoing complex therapy. Glioblastoma is a highly vascularized tumor, and the efficacy of regorafenib as an inhibitor of multiple protein kinases, including kinases involved in tumor angiogenesis, was studied in the phase II randomized, multicentre, open-label trial REGOMA. The article presents a brief review of the study and a clinical case of prescribing regorafenib in combination with bevacizumab in the 3rd line of therapy for a patient with glioblastoma without MGMT gene methylation and IDH1 and IDH2 mutations in the tumor. The time to progression was 5 months.