The prevalence of diabetes mellitus (DM) in our country is quite high. Most of them are type 2 diabetes. This pathology is characterized by a rather high disability and mortality. The main cause of deaths in type 2 diabetes are cardiovascular diseases – about 52.0%. An important reason for the development and progression of these complications is the lack of compensation for diabetes, which is currently a serious problem. Thus, according to statistics in Russia, the proportion of compensated patients with type 2 diabetes with a glycated hemoglobin level of less than 7.0% is only slightly more than half of all patients. The reasons for insufficient compensation of the disease may be such factors as the lack of patient education and self-control, as well as the patient’s low adherence to compliance with the rules for taking hypoglycemic drugs. The use of prolonged forms of drugs, as well as combined drugs, increases the adherence of patients to therapy. Among oral medications for the treatment of type 2 diabetes, the most commonly prescribed drugs are metformin and sulfonylurea (SM) derivatives. The joint appointment of these groups of drugs improves glycemic control of patients. There are drugs containing fixed combinations of metformin and SM derivatives. For example, containing 2.5 mg/tab of glibenclamide and 400 mg/tab of metformin, and 2.5 mg/tab of glib-enclamide and 500 mg/tab of metformin and 5 mg/tab of glibenclamide and 500 mg/tab of metformin, as well, containing 2 mg/tab of glimepiride and 500 mg/tab metformin. Such dosages are convenient for patient intake and further titration, also have a low risk of hypoglycemia.

Diabetes mellitus (DM) is an important medical and social problem throughout the world due to its high prevalence. At the same time, the majority of patients have type 2 diabetes. The onset of the disease is gradual, with a prolonged asymptomatic preclinical stage. Therefore, it is necessary to conduct screening among patients at risk. Therapy for type 2 diabetes is carried out with oral hypoglycemic drugs. If it is impossible with their help to achieve adequate glycemic control, it is possible to add basal insulin to therapy, and if the own insulin secretion is depleted, an intensive insulin therapy regimen must be prescribed. Insulin preparations differ in the source of receipt, as well as in the duration of action: background, or basal (insulin of medium duration, long-term or ultra-long-acting) and prandial, or food (ultrashort and short insulin). Currently, along with original insulin preparations, their analogues, or biosimilars (biosimilars), appear on the pharmaceutical market. Biosimilar (biosimilar) is a biological product similar in quality, efficacy and safety parameters to a reference biological medicinal product in the same dosage form and having an identical route of administration. Biosimilars are used all over the world, and this applies not only to insulin preparations, but also to other biological preparations. Proof of bioequivalence is a long-term process that ensures comparability and the absence of clinically significant differences between the study and the reference drug, and includes preclinical and clinical studies. The task of studies of biosimilars of insulin is to confirm the comparability with a reference, previously well-studied biological product. The efficacy and safety of domestically produced biosimilars has been studied in a number of clinical studies, during which the bioequivalence of the drugs was shown. These drugs are of high quality and safe, and their pharmacological characteristics, immunogenicity and effectiveness do not differ from the original drugs.

The article presents clinical study results of the efficacy and safety of combination therapy with sibutramine and metformin (fixed combination) in comparison with sibutramine therapy with microcrystalline cellulose in patients with alimentary obesity.The aim is to evaluate the efficacy and safety of using the sibutramine+metformin fixed dose combination (Reduxin® Forte) and compare it with the sibutramine + microcrystalline cellulose combination (Reduxin®) in patients with alimentary obesity in the course of the obesity therapy.Materials and methods. Male and female patients (240 people) aged 18 to 65 years inclusive with alimentary obesity, meeting the inclusion criteria and not meeting the non-inclusion criteria, were randomized into 2 groups in a 1:1 ratio. One group (n=120) received sibutramine+ metformin p. o., 1 tablet (850 mg + 10 mg) once per day, the second group (n=120) received sibutramine+ microcrystalline cellulose (MCC) p. o., 1 capsule (10 mg + 158.5 mg) once per day in the morning. On day 30 ± 1, in the absence of a 2 kg weight loss compared to the first visit, the dose was increased in accordance with the medical instruction. The therapy period was 180 days. The randomization list was generated by the factory method of random numbers. The efficacy and safety were assessed by anthropometric, clinical and laboratory parameters and the SF-36 questionnaire. The proportion of patients who achieved a decrease in body weight by more than 5% in 6 months, the magnitude and dynamics of changes in body weight and body mass index, waist and hip measurements, their ratios, changes in lipid profile, blood pressure, as well as the total number of adverse events, their frequency and nature of occurrence were analyzed.Results. The both drugs have demonstrated efficacy in all parameters of the obesity therapy. At the same time, in a comparative analysis, a statistically significant advantage of therapy with sibutramine + metformin was demonstrated in relation to the proportion of patients who had achieved more than 5% weight loss (body weight dynamics). Significant benefits were shown in terms of the magnitude of the change in body mass index (BMI); there was a statistically significant increase in the proportion of the patients who had switched from one category of BMI to another. By the end of the study, the vast majority of patients had no longer met the criteria for the diagnosis of “Obesity”. There was also a statistically significant benefit of sibutramine + metformin in terms of lowering triglycerides and low-density lipoprotein levels. The analysis of the safety parameters of sibutramine + metformin confirms a high safety profile of the drug, a comparative statistical analysis of adverse events in terms of their presence, severity, causal relationship with therapy and outcome have not revealed intergroup differences. Adverse events were transient and did not require discontinuation of therapy.Conclusion. The results of the study showed that therapy with Reduxin® and Reduxin® Forte provides a pronounced decrease in body weight. However, the use of a fixed combination has a more effective positive effect on the lipid profile and patients’ quality of life, which, combined with a high safety profile, proves the possibility and expediency of using Reduxin® Forte for the treatment of obesity and restoring metabolic health, even in patients without additional carbohydrate metabolism disorders.

Hypothyroidism is one of the most prevalent endocrine disorders, second only to diabetes. Hypothyroidism diagnosis can be difficult in view of its varied and non-specific symptoms. The reason is that thyroid hormones affect virtually every organ system in the body. At the same time, the severity of thyroid hormone deficiency may vary and does not always correlate with the changes in laboratory testing results. Clinical presentation of patients with hypothyroidism may include multiple symptoms and, as a result, it can be difficult to diagnose this disorder, especially in elderly and polymorbid individuals. In some patients, the prevailing symptoms indicate that only a particular system is affected. Thus, there are diseases known as the "masks" of hypothyroidism, and this review is focused on their clinical manifestations. Conditions that may be running under the "mask" of hypothyroidism include diastolic hypertension, dyslipidemia, hydropericardium, chronic constipation, biliary lithiasis, polyarthritis, alopecia, onycholysis, depression, dysfunctional uterine bleeding, infertility, anemia, etc. Due to a variety of clinical signs and symptoms, a patient with hypothyroidism may get an appointment with any medical specialist or receive a follow-up care provided in parallel by multiple specialists. Physicians should be aware of potential hypothyroidism and specific effects of the underactive thyroid on patient’s organs and systems. It is necessary to obtain a thorough medical history about comorbidities which would help to figure out that hypothyroidism is the cause of co-occurring conditions. KEYWORDS: autoimmune thyroiditis, hypothyroidism, subclinical hypothyroidism, euthyroidism, dyslipidemia, cardiovascular diseases, arterial hypertension FOR CITATION: Verbovoy A.F., Dolgikh Yu.A., Verbovaya N.I. Hypothyroidism is an interdisciplinary problem. Russian Medical Inquiry. 2022;6(9):509–515 (in Russ.). DOI: 10.32364/2587-6821-2022-6-9-509-515.

АНАЛИТИЧЕСКИЕ ОБЗОРЫЭндокринология считается относительно молодой медицинской наукой, становление которой произошло в конце XIX -начале XX в.Основоположник отечественной эндокринологии -профессор В.Д.Шервинский, который ввел преподавание заболеваний эндокринных органов.Он основал Государственный институт органотерапевтических препаратов, ставший в 1925 г.Институтом экспериментальной эндокринологии, ныне -ФГБУ «НМИЦ эндокринологии» Минздрава России.В последующем этим центром руководили академики Н.А.Юдаев, Ю

Introduction. Type 2 diabetes mellitus (DM) and hypothyroidism are the most common endocrine pathologies. These diseases are associated with atherogenic dyslipidemia, insulin resistance, and overweight.Aim. Тo assess the relationship between adipokines and hormone-metabolic parameters in women with hypothyroidism, type 2 diabetes mellitus and their combination.Materials and methods. We examined 119 women aged 45 to 74 years: 42 women with primary hypothyroidism, 38 women with type 2 diabetes and 39 women with a combination of type 2 diabetes and hypothyroidism. All patients underwent an anthropometric examination, studied the indicators of lipid and carbohydrate metabolism, the content of adiponectin, leptin and resistin.Results. In women with type 2 diabetes and its combination with hypothyroidism, hyperglycemia, hyperinsulinemia, and insulin resistance were revealed. In all groups, an increase in total cholesterol, triglycerides, atherogenic coefficient was found. The examined women with a combination of hypothyroidism and type 2 diabetes mellitus had a decreased level of adiponectin and an increased level of leptin. In patients with hypothyroidism and patients with type 2 diabetes, a decrease in adiponectin levels and an increase in leptin and resistin were revealed.Discussion. The most pronounced hyperinsulinemia and insulin resistance were found in the group of patients with a combination of hypothyroidism and type 2 diabetes. At the same time, the combination of type 2 diabetes and hypothyroidism in the examined women, according to our data, did not aggravate lipid metabolism disorders. Against the background of visceral obesity in women with a combination of diseases, hypoadiponectinemia and hyperleptinemia were most pronounced. In this group, the level of resistin was positively correlated with the level of insulin and the index of insulin resistance.Conclusion. In women with hypothyroidism, type 2 diabetes and their combination, atherogenic dyslipidemia, hyperleptinemia, and hypoadiponectinemia were established. Hypoadiponectinemia and hyperleptinemia are involved in the development of atherogenic dyslipidemia in women with primary hypothyroidism.

Abstract Background: Oral octreotide capsules (OOC; MYCAPSSA®) are approved in the US for individuals with acromegaly who responded to and tolerated treatment with injectable somatostatin receptor ligands (iSRLs). Add-on cabergoline therapy has shown effectiveness in patients previously inadequately controlled with iSRLS.1 The phase 3 MPOWERED trial assessed maintenance of response with OOC compared to iSRLs. Patients receiving OOC and ineligible for randomized controlled treatment (RCT) phase were eligible for a sub-study evaluating combination therapy with cabergoline, a dopamine agonist. Methods: Patients who fail to respond to 80 mg/d OOC for ≥2 weeks during the 26-week Run-in phase, or ineligible to enter the RCT on 80 mg/d OOC, due to inadequate biochemical control (insulin-like growth factor I [IGF-I] ≥1.3 × upper limit of normal [ULN] to <2 × ULN or IGF-I <1.3 × ULN and mean integrated growth hormone [GH] ≥2.5 ng/mL) were eligible for sub-study combination OOC 80 mg/d and cabergoline ≤3.5 mg/wk (fixed algorithm) for 36 weeks. End points included categorical changes in IGF-I and mean GH levels at sub-study end and adverse event (AE) incidence and severity. Echocardiogram was performed at sub-study start and every 12 weeks after. Results: Of 146 patients enrolled in MPOWERED, 14 entered the combination sub-study, 9 having IGF-I ≥1.3 × ULN at sub-study start. Final cabergoline doses were 1 (n=5), 2 (n=3), 3 (n=1), and 3.5 mg (n=5) with 25.4-week (SD, 14.1) mean treatment duration. Week 36 IGF-I improved in most patients (n=12; 85.7%). Of 9 patients with IGF-I ≥1.3 × ULN at sub-study start, 5 (55.6%; 95% CI, 21.2%-86.3%) exhibited IGF-I decreased to predefined responder range (<1.3 × ULN) by week 36. AE incidence and nature with combined treatment were similar to known octreotide safety profile and acromegaly disease burden. There were no serious AEs or AEs leading to discontinuation of either sub-study drug. Conclusion: We have shown for the first time the benefit of an all-oral combination treatment for acromegaly and avoidance of injection-related burdens. Addition of cabergoline to OOC yielded biochemical control improvement (IGF-I reduction) in patients inadequately controlled with OOC monotherapy. As both combination and OOC monotherapy safety profiles were similar, adjunctive cabergoline may be helpful in patients with acromegaly who do not achieve adequate biochemical control on OOC alone. 1Giustina A, et al. Nat Rev Endocrinol. 2014;10(4):243-248.

Hypothyroidism is one of the most common diseases of the endocrine system. It is more often recorded in older women. This disease is characterized by nonspecific symptoms and a blurred clinical picture. Patients often have many symptoms from various organs and systems. Because of this, hypothyroidism often remains unrecognized, and patients are not prescribed the necessary therapy on time. Doctors of various specialties should pay attention to the symptoms that may manifest as hypothyroidism. This is especially true for elderly patients. As a screening, the definition of thyroid-stimulating hormone (TSH) is used. First of all, attention should be paid to the pathology of the cardiovascular system, the presence of arterial hypertension, often diastolic and poorly controlled, a decrease in stroke volume and heart rate. Also, in hypothyroidism, lipid metabolism disorders, an earlier onset of atherosclerosis, a connection with metabolic syndrome and type 2 diabetes mellitus were noted. Therefore, it is recommended to diagnose hypothyroidism in patients with these diseases. Screening should also be done in the presence of neurological disorders, depressive and anxiety disorders, gastrointestinal diseases, and hematological disorders (anemias). The determination of TSH is included in the examination plan for infertility, and may also be necessary for other disorders of the reproductive system: menstrual irregularities in women and androgen deficiency in men. Treatment of overt hypothyroidism consists in the appointment of replacement therapy with levothyroxine. If subclinical hypothyroidism is detected, the question of treatment is decided individually and depends on the level of TSH, the patient’s age, and the clinical manifestations of the disease.

Metabolic syndrome is a symptom complex that is based on visceral obesity and insulin resistance. Its prevalence is quite high, which is a big problem, since this condition increases the risk of developing cardiovascular diseases and mortality from them. Metabolic syndrome includes, in addition to abdominal obesity, arterial hypertension, disorders of carbohydrate, lipid and purine metabolism. Visceral adipose tissue plays a key role in the formation of insulin resistance and other components of the metabolic syndrome. This is due to the fact that abdominal fat, in contrast to subcutaneous fat, synthesizes pro-inflammatory cytokines, as well as adipokines — adipose tissue hormones that are involved in the formation of insulin resistance, affect carbohydrate and fat metabolism and the cardiovascular system. These include leptin, adiponectin, resistin, apelin and others. Some adipokines have an adverse effect on metabolism and increase cardiovascular risks, while others, on the contrary, have a positive effect. Taking into account their role in the development of the components of the metabolic syndrome, the possibilities of a therapeutic effect on the hormones of adipose tissue to improve metabolic processes and prevent complications associated with it are discussed.

Diabetic autonomic neuropathy is the second most common form of damage to the nervous system in diabetes mellitus as a result of disorders of the central and/or peripheral parts of the autonomic nervous system. On average, its frequency of occurrence is about 40%, and 60% or more with an increase in the duration of diabetes over than 10 years. Diabetic autonomic neuropathy is characterized by polysyndromism of clinical manifestations. In this regard, a number of forms of diabetic autonomic neuropathy are distinguished both in the form of an isolated violation of the function of organs and systems, and with their combined defeat. In the pathogenesis of autonomic neuropathy, vascular and metabolic changes common to the development of diabetic polyneuropathy play an important role. The most significant risk factors for the development of diabetic autonomic neuropathy are the patient's age, duration of diabetes mellitus, and a higher average HbA1c. The development and progression of diabetic autonomic neuropathy depends on glycemic control, but its forms such as gastrointestinal and impaired recognition of hypoglycemia (asymptomatic hypoglycemia) can cause poor compensation for diabetes. This article discusses the various clinical manifestations of gastrointestinal autonomic neuropathy. Attention is drawn to the fact that the clinical picture is often nonspecific and asymptomatic, which complicates timely diagnosis. The gastrointestinal form of diabetic autonomic neuropathy leads to limited performance, social maladaptation of patients, dramatically reduces the quality of life of patients with diabetes mellitus. In clinical practice, the doctor must remember that it can significantly affect the achievement of glycemic control, as a result of a violation of the digestion and passage of food, as well as a violation of the pharmacokinetics of hypoglycemic drugs. Impaired recognition of hypoglycemia also makes it difficult to compensate well. These complications require a personalized approach to the patient from the doctor, and strict and frequent self-control of glycemia with the help of a modern glucometer from the patient to maintain optimal glycemic control and prevent possible hypoglycemic conditions.

In medical practice, there are often patients who have several diseases at once, both pathogenetically related to each other and not related. The article discusses endocrine diseases in which there are manifestations from the cardiovascular system - disorders of carbohydrate metabolism, pathology of the thyroid gland, adrenal glands and acromegaly. These diseases reduce the quality of life of patients and increase the risks of cardiovascular complications. The article also discusses the features of cardiovascular manifestations in these diseases and indications for differential diagnosis. Type 2 diabetes mellitus significantly increases the cardiovascular risks, which leads to a more rapid progression of atherosclerosis. Moreover, vascular disorders are detected already at the stage of prediabetes. Therefore, it is necessary to identify disorders of carbohydrate metabolism as early as possible and initiate appropriate therapy. When prescribing antihyperglycemic therapy, preference should be given to drugs with a low risk of hypoglycemia (metformin, glucagon-like peptide-1 agonists, type 2 sodium glucose co-transporter inhibitors). Thyroid dysfunctions - thyrotoxicosis and hypothyroidism - also have an adverse effect on the cardiovascular system. Hypothyroidism often has a blurred clinical picture and manifestations from various organs, and therefore it is diagnosed late. Therefore, an active diagnosis of this condition should be carried out in persons with a combination of a wide variety of diseases, especially in old age. Adrenal pathology (pheochromocytoma, hyperaldosteronism and hypercorticism) is manifested by an increase in blood pressure. Differential diagnosis is worthwhile in case of severe arterial hypertension or resistance to antihypertensive therapy. In acromegaly, lesions of the cardiovascular system are quite common and are the main cause of death in these patients. Therefore, early detection of this pathology is especially important. Thus, such patients should be monitored jointly by a cardiologist and an endocrinologist, and timely diagnosis and treatment of endocrine pathology will help reduce their cardiovascular risks.

Hypothyroidism is the most common endocrine disease after diabetes mellitus. Its frequency depends on age, sex and iodine intake. The highest prevalence of hypothyroidism is observed in older women. Chronic autoimmune thyroiditis is the most common cause of this condition. The peculiarity of hypothyroidism is an erased clinical picture, diversity and nonspecific symptoms. This makes it difficult to diagnose the disease, leads to an erroneous diagnosis and later detection of thyroid insufficiency. This article discusses the various «masks» of hypothyroidism and peculiarities of clinical manifestations. The main «masks» are: cardiological, dermatological, urological, gastroenterological, endocrine and reproductive system disorders, neurological, psychiatric, hematological, rheumatological. Free thyroxine and thyroid-stimulating hormone are used to diagnose hypothyroidism, as well as antibody titer to thyroid peroxidase and thyroglobulin to detect chronic autoimmune thyroiditis. Levothyroxine preparations are used as a substitution therapy. The dose of the drug depends on the age of the patient and the presence of cardiovascular disease. Patients under 50 years of age without a severe concomitant cardiovascular disease are given 1.6 µg of levothyroxine per kg of body weight. In persons over 50 years of age with cardiovascular diseases, the drug dose is prescribed at the rate of 0.9 µg per kg of body weight. The therapy starts with small doses, slowly increasing it under the control of electrocardiography. At occurrence or strengthening of symptoms of angina a dose of levothyroxine is reduced to the previous one and the cardiovascular therapy is corrected. Evaluation of the effectiveness of the treatment is carried out on the level of thyroid hormone.

Diabetes mellitus (DM) type 2 is the serious progressing chronic disease representing independent risk factor of development of cardiovascular complications. The mortality from cardiovascular diseases at the persons suffering from DM type 2 continues to grow around the world, despite constant augmentation of expenses on treatment and prophylaxis. In this article factors of cardiovascular risk at DM are analyzed and possible ways of their correction are surveyed.

Today an obesity became the global epidemic striking both children, and adults and represents one of the most important problems of health care worldwide. Excess accumulation of fatty tissue is resulted by insulin resistance and a compensatory hyperinsulinaemia which are the main predictors of development of a diabetes mellitus type 2. Insulin resistance is also one of key links of a pathogenesis of such diseases as cardiovascular pathology, not-alcoholic fatty liver disease, a polycystic ovary syndrome, gestational diabetes and many others. Depression of sensitivity of tissues to insulin can be physiological reaction of an organism to stress factors and pathological process. The endogenic reasons also take part in development of insulin resistance besides factors of the external environment. The role of genetic predisposition, a subclinical inflammation of fatty tissue, thyroid hormones, adipokines and vitamin D in formation of this pathological process is studied. As insulin resistance takes part in a pathogenesis of various diseases, methods of its diagnostics and correction are of great importance in therapeutic practice. At purpose of treatment it is worth giving preference to the drugs which are positively influencing sensitivity of tissues to insulin.

Adipose tissue is an active endocrine organ secreting a number of hormones adipokines. One of them is resistin, which is produced not only by adipocytes, but also by monocytes, macrophages, cardiomyocytes. Since the beginning of its discovery in 2001 the effect of this adipokine on insulin resistance has been studied. However, later his role in the initiation of inflammatory reactions, activation of the endothelium, proliferation of smooth muscle cells of the blood vessels have been researched, and therefore resistin began to be considered as a possible marker of cardiovascular pathology. This review article presents data on resistin in terms of its effect on the development and progress of cardiovascular diseases.

The adipose tissue is an endocrine organ producing large amounts of hormone-like substances, such as adipokines . Their properties, biological and pathophysiological effects have recently attracted much attention of researchers. This review article is focused on resistin and its role in the development of insulin resistance, cardiovascular diseases, and atherosclerosis.

Osteoprotegerin (OPG) is a glycoprotein that is a representative of the tumor necrosis factor-α receptor superfamily. Information about the possible role of OPG in the development of cardiovascular diseases has begun to appear in the literature in recent years. This review discusses the role of increasing the level of OPG in the development and progression of atherosclerosis and as a consequence of coronary heart disease and chronic heart failure.

Obesity is a serious medico-social and economic problem. Increased body mass index is associated with a rise in the general mortality rate and mortality due to cardiovascular diseases. In this article, modern views of the influence of obesity on the cardiovascular system are considered.

As of now, osteoporosis (OP) is one of the most important sociomedical problems because of its high prevalence and resultant disability, as well as significant mortality attributable to complications. The current strategy for providing care for patients of OP is its early diagnosis, by determining the high risk of fractures, and early pathogenetic treatment. The article gives an update on the epidemiology, risk factors, diagnosis, and treatment of OP.