Original studies
Background: The diagnostic threshold of β-hydroxybutyrate (BHB) at the moment of hypoglycemia in insulinoma was developed for venous blood many years ago, when there were no alternative ways to measure ketones. Number of works, mainly on patients with diabetes mellitus, found differences in the measurement of this indicator in venous and capillary blood, but the results were contradictory. Moreover, this study was not previously used in the diagnosis of non-diabetic hypoglycemia (NDH) in adults on the territory of the Russian Federation.
Aim: To estimate the effectiveness of the method for determining BHB in capillary blood and its place in the diagnosis of NDH.
Materials and methods: We conducted an experimental, cross-sectional, comparative study and included patients with suspected NDH who underwent a standard fast test. The BHB level in capillary blood was determined every 6 hours during the fast test and at its completion.
Results: Based on the results of the fast test, the participants (n=154) were divided into groups: with hyperinsulinemic variant of NDH and IFRoma (n=98; group 1), with hypoinsulinemic variant of NDH /absence of NDH (n=56; group 2). When comparing the level of BHB at the moment of fasting completion, significant differences were obtained between groups 1 and 2 (p<0.001). According to the ROC analysis, the determination of BHB for differentiation the hyper- and hypoinsulinemic variants of hypoglycemia is characterized by excellent quality of model (AUC=99,1% [98,0%; 100,0%]). The BHB determination in capillary blood has the maximum diagnostic accuracy at a cut-off point of ≤ 1.4 mmol/L (Se 98.0%, Sp 96.4%, PPV 98.0%, NPV 96.4%, Ac 97.4%). Exceeding the diagnostic threshold of BHB was first recorded after 24h of fasting; at the same point, a significant difference was determined when comparing BHB indicators between two consecutive measurements (between 18h and 24h).
Conclusion: The BHB determination in capillary blood is a highly sensitive and highly specific additional method for the differential diagnosis of NDH variants. The diagnostic threshold for BHB of capillary blood, which allows differentiating hyper- and hypoketonemic variants of NDH, is ≤1.4 mmol / L. It is advisable to initiate control of BHB in the blood no earlier than 18 hours after the start of the fast test.
Background: Assessment of resting energy expenditure (REE) is necessary for the formation of a diet for obesity patients. The «gold standard» for assessment of resting energy expenditure (REE) is indirect respiratory calorimetry. Currently, bioimpedance analyzers are increasingly being used in clinical practice to assess energy consumption at rest, including in obese children. However, the accuracy of such an assessment remains unclear.
Aims: To determine the accuracy of the assessment of resting energy expenditure using bioimpedance analysis in children with simple obesity compared with indirect respiratory calorimetry.
Materials and methods: Resting energy expenditure was assessed by bioimpedance analysis, Harris-Benedict formula and indirect respiratory calorimetry in all obese children. Comparability of methods was assessed using the Bland-Altman analysis.
Results: The study included 320 children aged 7 to 17 years with simple obesity.Resting energy expenditure assessed by bioimpedance analysis was on average 232 kcal lower than the actual. A significant CI (-448 to 912 kcal) was revealed, as well as a large LOA from -514 to 979 kcal. REE calculated by the Harris-Benedict formula on average corresponded to the actual one, and CI varied from -38 to 27 kcal. However, large LOA from -514 to 979 kcal, indicating a high individual variability of resting energy consumption.
Conclusions: Bioimpedance analyzers underestimate REE in obese children compared to indirect respiratory calorimetry and the Harris-Benedict formula. Given the significant discrepancies in the accuracy of REE assessment, bioimpedance analysis cannot be considered as an alternative to indirect respiratory calorimetry to assess resting energy in children with simple obesity.
Background: Studies of the relationship between obesity and functional bowel disorders, carried out in different age groups, provide conflicting results. It remains unclear what factors are responsible for the transition from a tendency to constipation in children to a tendency to diarrhea in adults with obesity.
Aim: To establish factors related to stool consistency as a surrogate marker of colon transit in adolescents with obesity.
Materials and methods: A single-center observational cross-sectional study was carried out. We consecutively recruited adolescents, aged 11–17 years with obesity. Socio-demographic characteristics, lifestyle and nutritional characteristics were assessed using questionnaires. Bowel symptoms were assessed using questionnaires and interviews. Stool consistency was assessed using the Bristol Stool Form Scale. Serum concentrations of ALT, AST, bilirubin, cholesterol, glucose, HbA1c, leptin, and insulin were determined. The HOMA-IR index was used to determine insulin resistance.
Results: One hundred and ten adolescents with obesity were enrolled in the study. Of these, 69.1% had a pathological consistency of feces, with the prevalence of forms characterizing delayed gut transit (49.1%). The predominance of loose stools was reported by 5.5% of patients. The combination of different forms of stool (unstable stool) was described by 14.5% of adolescents. Hard stools were common among adolescents from single-parent families and adolescents who rarely consume dairy products. The presence of loose stools has been associated with insulin resistance.
Conclusion: Most obese adolescents who do not have abdominal complaints have colon transit disorders. Medical professionals should actively ask these patients about stool frequency and properties. With constipation, dietary correction is justified. Research is needed to investigate in-depth gut microbiota as a possible link between obesity and diarrhea.
Background: Disturbance of the morphological and functional properties of the vascular bed in obesity are a serious clinical problem. Basis to their development is endothelial dysfunction. The developed models of obesity in animals using various diets indicate a change in vascular reactivity, however, questions about the stage at which this occurs and what mechanisms are involved in this process remain open, while they are decisive for choosing the correct tactics for correcting dysfunctions.
Aim: The aim of the present study is to determine the changes in acetylcholine (ACh)-induced vasodilation of isolated arteries from rats after six weeks of administration of a high-fat diet (HFD).
Materials and methods: The experiments were performed on Sprague-Dawley males, which at the age of 8 weeks were divided into 2 experimental groups that were treated for the next 6 weeks in the following manner: 1 - control) with standard dry food; 2 - a group fed with a HFD, the total amount of fat in which was 50%. At finish of the diet, the degree of obesity, biochemical parameters in the blood, and blood pressure were measured. Intravital microscopy of the rat mesentery with video recording was used to study the reactivity of the vessels. The contractile and relaxant responses of the vessels were determined by changes in their diameter.
Results: The rats after treatment with the HFD (n=15) had higher body weight and amount of visceral fat, significantly increased blood triglycerides, moderate increases in glucose level in blood and systolic pressure compared with the control (n=15). Relaxation responses of mesenteric arteries, having a diameter of 140 to 300 μm in PSS, were recorded after precontraction by phenylephrine. A decrease in ACh-induced vasorelaxation was obtained, which manifests itself before the development of significant changes in carbohydrate metabolism. Incubation of drugs with the inhibitor of endothelial NO synthase L-NAME led to a pronounced weakening of relaxation in animals on a standard diet, and had little effect on vasodilation in the arteries of rats with the HFD. Vasodilation induced by the administration of sodium nitroprusside (NO donor) did not differ significantly in control and experimental animals, which indicates that the sensitivity of vascular smooth muscle to NO remained practically unchanged. ACh-induced relaxation of arteries in dietary rats did not change when the cyclooxygenase pathway was blocked by diclofenac.
Conclusion: Functional changes in the contractile activity of the mesenteric arteries, manifested in the form of a decrease in ACh-induced vasorelaxation, occur after treatment with the HFD when animals had an early stage of obesity development before the onset of pronounced disorders of carbohydrate metabolism. This decrease is mainly due to the disruption of the NO-dependent mechanism underlying ACh-induced relaxation in the norm.
Background: The article shows that the development of obesity and associated health disorders is directly related to the changes in eating behavior (EB) and the psychoemotional state. However, the considered studies were carried out in obese patients of medical institutions only. The research in young people focuses mainly on the sociological and psychological aspects of EB.
Aim: To study the psychological characteristics, eating behavior features and their relationship with the indicators of actual nutrition and the body composition in young men.
Materials and methods: A multicenter, cross-sectional sample survey of young men aged 17 to 21 was performed. A survey of violations of the EB was carried out, on the basis of which 5 groups of young men were formed. Group 1 (comparison) consisted of young men without violations of the EB. Group 2 consisted of young men with impaired emotiogenic EB. Group 3 consisted of boys with violations of the restrictive PP; group 4 — young men with impaired external EB; group 5 — young men with a combination of impairment of emotionogenic and restrictive EB. We used the Dutch DEBQ questionnaire to study the types of eating behavior. The current mental state of the testees was evaluated by a clinical and psychological test — Symptom Checklist-90-Revised (SCL-90-R). The body composition was assessed with the ABC-01 «Medass» bioimpedansometry device. The «Analysis of the human nutritional state” computer program was applied to estimate the actual nutrition by the frequency analysis method.
Results: The study included 96 volunteers. Young men with impaired external EB feature an increase in the daily average energy consumption, which resulted in an increase in BFM%. In young people with eating disorders, an increase in scores on the «Somatization», «Obsession-compulsion», and «Anxiety» scales as compared to the reference valuesis testified. The depression level in young men correlated with the severity of emotiogenic eating behavior (r = 0.455, p <0.001).However, it is associated with the severity of external EB to a greater extent (r = 0.608, p <0.001). On the contrary, the anxiety level more strongly correlated with the severity of emotiogenic EB (r = 0.575, p <0.001) rather than of external EB type (r = 0.391, p <0.001).
Conclusion: EB disorders in young men are associated with psychophysiological features, eating disorders accounting for the accumulation of adipose tissue in the body.
CASE REPORT
ACTH — ectopic syndrome (ACTH-ES) is a severe multisystem disease caused by paraneoplastic secretion of ACTH itself and/or much less often corticoliberin (CL) by tumor tissue. The frequency of ACTH-ES is 12–20% of cases of endogenous hypercortisolism, i.e. about 1–2 cases per million population, and covers a range of tumors, from benign neoplasms to malignant tumors with widespread metastases, while the most common causes of ACTH-ES are tumors of the lung, pancreas and thymus, and more rare localizations are neuroendocrine tumors (NET) of the intestine, medullary thyroid cancer, pheochromocytoma and mesothelioma. The optimal treatment for ACTH-ES is to remove the ACTH-secreting tumor. For patients with an unidentified source of ectopic hormone secretion, the choice is narrowed to bilateral adrenalectomy followed by hormone replacement therapy with glucocorticoids and mineralocorticoids. Medication options are generally a low-effective/palliative treatment option. In this article, we present a clinical case of the successful use of long-acting octreotide in a 36-year-old woman with severe ACTH-ES for long-term control of paraneoplastic ACTH secretion, against which a clinical and biochemical improvement comparable to complete remission of the disease was achieved.
Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly.
Hypoparathyroidism is an endocrine disease caused by damage of the parathyroid glands and characterized by underproduction of parathyroid hormone. This can lead to severe hypocalcemia and its associated complications. The chronic hypoparathyroidism requires lifelong therapy including calcium and vitamin D analogues. The goal of treatment is to maintain the target parameters of phosphorus-calcium metabolism. At the same time, there is a risk of iatrogenic hypercalcemia on the standard therapy, up to the hypercalcemic crisis, often complicated by the acute renal failure. Moreover, chronic hypercalcemia acts as a predisposing factor for nephrolithiasis, nephrocalcinosis, chronic renal failure including pre- and dialysis stages.
Dihydrotachysterol is a synthetic analogue of vitamin D, which was previously widely prescribed for hypocalcaemic hypoparathyroidism. In accordance with modern Russian and international guidelines, this drug should not be used in the treatment of chronic hypoparathyroidism. The main features in the metabolism of dihydrotachysterol (long elimination period, lack of feedback regulation of the active metabolites, high biological activity) and a narrow therapeutic window cause the frequent development of hypercalcemia and associated disorders.
We present several clinical cases of patients with hypoparathyroidism treated with dihydrotachysterol, which was complicated by severe hypercalcemia and acute renal failure.
REVIEWS
Non-alcoholic fatty liver disease currently affects more than 30% of the population. Recent studies highlight the role of genetic polymorphisms in genes associated with fat catabolism and anabolism in the manifestation of this condition and its progression. The work analyzes foreign publications on the molecular and biochemical aspects of these polymorphisms, as well as works studying their effect on the state of the liver and markers of its pathology over the past 10 years. Thus, polymorphisms of the PNPLA3, MBOAT7, and TM6SF2, affecting the functionality of the proteins they express, lead to a change in the metabolism of fatty acids in the liver, which in turn leads to the development of NAFLD and its progression. Despite the fact that the contribution of the rs738409 polymorphism of the PNPLA3 gene is well described both in foreign and Russian articles, polymorphisms of the MBOAT7 and TM6SF2 genes and their effect on NAFLD, as well as the molecular biochemical mechanisms underlying it, have been studied much worse in foreign studies and are little mentioned in Russian ones. In addition, the issue of the severity of the influence of the above polymorphisms on populations of different ethnic and age groups requires additional research. This work attempts to systematize the available data on these issues.
The SARS-CoV-2 virus that caused the 2019 new coronavirus infection (COVID-19) pandemic has posed an unprecedented challenge to the global health system and scientific community. As of this literature review, the infection has claimed more than 6 million lives, and more than 500 million people worldwide have already been infected with SARS-CoV-2. In addition to the basic, pulmonary manifestations of the disease, as well as the severe, life-threatening complications of acute COVID-19, the long-term changes that occur in the postcovid period also affect other systems: endocrine, cardiovascular, nervous, and musculoskeletal. In this literature review, using data from current scientific publications obtained by searching «covid-19 endocrine disorders», «postcovid endocrine disorders» and «postcovid syndrome endocrine disorders» in the MEDLINE (PubMed) database and «endocrine pathology and covid-19», «postcovid and endocrine pathology» and «postcovid syndrome and endocrine disorders» in the e-Library database, we focused on describing and discussing the complications and consequences that SARS-CoV-2 infection can have on the endocrine glands, including the adrenals, thyroid, pituitary, gonads and pancreas.
Obesity is an uprising trend across the world resulting in huge costs for healthcare systems and declines in the quality of life in patients. Bariatric surgery is one of the most effective approaches to weight loss. Although bariatric surgery can be considered as a minimally invasive approach it has a series of complications such as weight regain 1 to 4 years after surgery. Nonetheless, most patients achieve sufficient weight loss, but the other subjects with supervised strategies would be able to manage food intake and change problematic lifestyles to continue the weight loss process. In this review article, we aim to gather valuable interventions performed and reported by researchers to manage weight regain in bariatric patients. Weight regain is a multi-factorial condition owing to hormonal imbalances, nutritional deficiencies, physical inactivity, mental health disorders, problematic dietary behaviors, medical issues such as thyroid, adrenal, kidney, or heart problems, taking new medications, diabetes relapse, and pregnancy, as well as anatomic and surgical factors. Therefore, its remission needs interdisciplinary approaches.
The article presents some of the most relevant strategies of healthcare management: patient-oriented and value-oriented approaches, 4P concept and CRM (the concept of patient relationship management). It provides a review of modeling an efficiant interaction in doctor-patient dyad based on systemic analysis, in other words — via management by goals and values. It also suggests a direction of psychotherapeutic influence over prevention and treatment of obesity. They provide examples of complex studies of treating overweight and obesity, in particular — international programs LOOK AHEAD (Action for Health in Diabetes), 2014 and Duke University program, 2019, as well as the domestic «Life is light» study, conducted together with FSBI «NMIC of Endocrinology» of Russian MoH with support of the Novartis group. The text contains the authors’ experience of successful psychotherapeutic support of patients with obesity in ‘health coaching’ format, including its main task: changing the system of beliefs, building tolerance to change and increasing self-efficacy of an individual. The article provides analysis of the results and the possible areas for replicating the experience of the team into applied activities of treating patients with overweight and obesity.
Hypogonadism is a condition associated with a decrease in the functional activity of the testicles, accompanied by a decrease in the level of androgens and (or) a violation of the process of spermatogenesis. It is known that androgens and their main representative, testosterone, are of fundamental importance for the development and maintenance of the reproductive and sexual functions of the male reproductive system. At the same time, low testosterone levels are associated with both reproductive and metabolic disorders, including phosphorus-calcium, fat, carbohydrate, and protein metabolism. In addition, to date, data have been accumulated on the correlation of hypogonadism with cardiovascular diseases, which once again emphasizes the problem of testosterone deficiency, especially for patients of the middle and older age groups. However, carrying out testosterone replacement therapy always requires a strict and competent choice of a «target audience» among patients from a specialist. Today, on the pharmaceutical market, there is a wide arsenal of testosterone-containing drugs in various forms for use, which have an unequal «efficacy-safety» profile. In this review, we have analyzed modern approaches to the diagnosis and treatment of hypogonadism, the selection of a target group of patients to obtain the most effective and safe treatment outcome and described testosterone preparations and their dosage forms with potential advantages and disadvantages. Thus, the information presented in the article is aimed at optimizing the management of men with hypogonadism.

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