Differential diagnosis of hypercalcemia in a patient with CKD G5D

Patients with chronic kidney disease are characterized by the development of mineral disorders due to a decrease in the number of functioning nephrons. These changes manifest by the development of secondary hyperparathyroidism (the overproduction of intact parathyroid hormone (PTH) associated with the serum hypocalcemia, hyperphosphatemia), dysfunctional vitamin D metabolism, bone mineralization and also extraosseous calcifications. Decreased serum PTH levels associated with hypercalcemia are suspicious for adynamic bone disease, but at the same time requires an extended differential diagnostic search (e.g. metastatic processes). One of the rare causes of hypercalcemia is a defect in 24-hydroxylase (CYP24A1). We present a case of a patient on hemodialysis with atypical secondary hyperparathyroidism and an established CYP24A1 defect.

Lymphatic system and adipose tissue: Crosstalk in health and disease

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

Ejaculate quality indicators of men with asthenozoospermia and asthenoteratozoospermia by treatment of obesity with liraglutide

Background: Considering the influence of visceral obesity on male infertility, the investigation of ejaculate quality indicators under obesity treatment is relevant.Objective: Evaluation of ejaculate quality indicators by obesity treatment with liraglutide in andrologically healthy men with infertility and post-pubertal visceral obesity.Methods: Infertile men with post-pubertal alimentary visceral obesity were included in a pilot observational prospective study. All patients were given recommendations for body weight loss (hypocaloric diet, daily aerobic physical activity) as well as an average daily dose of liraglutide 2.4 [2.4; 3.0] mg. Evaluation of waist circumference, antioxidant activity of ejaculate, spermogram was carried out initially and after 6 months. The differences were considered statistically significant at p <0.005.Results: The body weight decrease was -11.7 [12.4; 11.0]%, the waist circumference decrease was 8 [12; 7] cm. In dynamics, increased content of living sperm in ejaculate from 92 [90; 95]% to 95 [92; 98]%, morphologically normal forms from 5 [3; 6]% to 6 [3; 8]%, mobility of A + B from 25 [15; 36] to 35 [19; 52]%, seminal antioxidant capacity, a decrease in reactive oxygen forms in the neat ejaculate were statistically significant. Increasing the sperm count in 1 ml and decreasing reactive oxygen forms in the washed ejaculate did not reach statistical significance.Conclusion: Ejaculate quality indicators improved by the complex obesity therapy with liraglutide in young andrologically healthy men with postpubertal visceral obesity.

Adipose tissue: colors, depots and functions

Obesity is a chronic disease characterized by excessive accumulation of adipose tissue. The prevalence of obesity and associated diseases has prompted researchers to expand the study of the biology of adipose tissue. New technologies have significantly expanded the understanding of adipogenesis mechanisms, various aspects of lipid and glucose metabolism, as well as the paracrine and endocrine functions of adipose tissue. Adipose tissue is a complex, heterogeneous endocrine organ. The existence of several shades of adipocytes demonstrates their morphological and functional heterogeneity. The main function of white adipose tissue is to store energy. Brown and white adipocytes perform a predominantly thermogenic function. Bone marrow (yellow) adipose tissue regulates the processes of bone remodeling and hematopoiesis. Pink adipocytes are formed during pregnancy and satisfy the energy needs of the offspring. The study of the biology of adipose tissue is crucial to understanding the pathophysiology of obesity and determining its molecular relationships with type 2 diabetes as well as cardiovascular and oncological diseases. The review presents current literature data on the origin, adipogenesis, and functional properties of adipose tissue depending on its cellular composition and localization. It outlines the nature of changes in adipose tissue in obesity and the clinical significance and therapeutic potential of various adipose tissue depots.

Endocrine disruptors in the pathogenesis of socially significant diseases such as diabetes mellitus, malignant neoplasms, cardiovascular diseases, pathology of the reproductive system

Some environmental chemicals capable of interfering with the endocrine regulation of energy metabolism and the structure of adipose tissue in the function of the reproductive, immune, cardiovascular and other systems are called endocrine disruptors or disruptors. According to the WHO definition, the term «endocrine disruptors» means: «Exogenous substances or mixtures thereof that alter the function (s) of the endocrine system and, as a result, cause adverse effects in the intact organism or in its offspring, or (sub) population.» This includes compounds to which humanity is exposed in daily life as a result of their use in pesticides, herbicides, industrial and household products, plastics, detergents, refractory impregnations and as ingredients in personal care products. This review will present the latest scientific data on various ERs, such as persistent organic pollutants (POPs): pesticides (mirex, chlordecane, endosulfan, hexachlorobenzene-HCB dichlorodiphenyltrichloroethane-DDT and its metabolites), industrial chemicals (bisphenol A, polybrominated ether -PBDE, polychlorinated biphenyls-PCB, nonylphenol, dioxins, perfluorooctanoic acid-PFOA, phthalates), pharmaceuticals (diethylstilbestrol-DES). ERs are regarded as compounds that cause obesity, since they have the ability to influence cellular processes associated with adipose tissue, initiating changes in lipid metabolism and adipogenesis. Analysis of scientific materials on this issue indicates that ERs are ubiquitous in the environment and have a detrimental effect on the health of animals and mankind. The scientific and practical interest in this article is based on the growing statistics of the development of such socially significant pathologies as obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, menstrual irregularities, as well as cancer and infertility, for of which obesity is a risk factor.

Metabolic endotoxemia: possible causes and consequences

This review article presents data from the literature, which provide an idea of the relationship between metabolic disorders occurring against the background of obesity and endotoxinemia, as well as the effect of these conditions on the maintenance of low-grade inflammation in the body. A description of the hormonal and immune restructuring of white adipose tissue, the main routes of entry and metabolism of endotoxin is given. Particular attention is paid to the mechanisms of the mutual influence of obesity and endotoxinemia. Described by Yakovlev M.Yu. in 1988 «endotoxin aggression» and Cani P.D. et al. in 2007, «metabolic endotoxinemia», in our opinion, is one of the most important triggers for the development and progression of a whole spectrum of acute and chronic diseases. Based on the data of recent years, adipose tissue is an active endocrine organ capable of influencing both metabolic processes and the state of innate and acquired immune defense mechanisms. It has now been proven that high-calorie diets lead not only to an increase in overweight, but also to an increase in the level of endotoxin circulating in the blood. An in-depth study of the ability of obesity and endotoxinemia to potentiate the mutual pro-inflammatory effect can help both in understanding the pathogenesis of the main cardiovascular, autoimmune, allergic and infectious (including viral) diseases, and in the development of methods for non-pharmacological and drug correction of these conditions.

The results of immunohistochemical study of antibodies to CYP11B2 in primary hyperaldosteronism

Background: Aldosterone-producing adrenocortical adenoma (APA) is responsible for the majority of cases clinically diagnosed as primary aldosteronism. Aldosterone synthase (CYP11B2) is one of the enzymes that play essential roles in aldosterone synthesis and is involved in the pathogenesis of primary aldosteronism. Recent studies have demonstrated that various factors influence the expression and function of CYP11B2 in APA. In particular, somatic mutations, such as gain-of-function and loss-of-function mutations have been identified in several genes, each of which encodes a pivotal protein that affects the calcium signaling pathway, the expression of CYP11B2, and aldosterone production. On the other hand, CYP11B2 also catalyzes the conversion of cortisol to 18-hydroxycortisol and subsequently converts 18-hydroxycortisol to 18-oxocortisol. The article also discusses the clinical significance of 18-oxocortisol, an important biomarker for the diagnosis of primary aldosteronism. Somatic mutations in aldosterone-driver genes are strongly associated with CYP11B2 expression and have been only detected in the CYP11B2-positive tumor area, that indicating heterogeneous expression of CYP11B2 in tumor.Aim: to assess the functional heterogeneity of adrenal tumors in primary aldosteronismMaterials and methods: Retrospective evaluation adrenal tumors from patients with primary aldosteronism (n=20). According to CT unilateral macrohyperplasia was detected in 19 patients (95% of total), all of them were confirmed to have unilateral hyperproduction of aldosterone according to AVS. Selected tumors werestained with anty-CYP11B2 antibody. We evaluated the CYP11B2 expression in the adenoma and in the adjacent adrenal cortex.Results: Immunohistochemistry studies of the resected adrenals from 20 patients with PA operated due to unilateral production of aldosterone using CYP11B2 staining showed that 10 of those with an adenoma on CT scanning showed CYP11B2 staining in the adenoma. Furthermore, 5 cases of an unilateral adenoma, showed CYP11B2 staining in the adjacent adrenal cortex and an absence of staining for CYP11B2 in the adenoma. 5 cases showed CYP11B2 expression is heterogeneously immunolocalized throughout the tumor area.Conclusion: Thus, the functional heterogeneity of adrenal tumors in primary aldosteronism has been proven. It is necessary to compare the data of immunohistochemical studies on the expression of CYP11B2 with the indicators of the level of 18-hydroxycortisol, 18-oxocortisol.

The frequency and structure of metabolic disorders in obese women in combination with polycystic ovary syndrome

Background: Obesity is considered a global epidemic and is one of the most significant medical and social problems. Research in recent years shows that in 25-45% of cases of obesity, polycystic ovary syndrome (PCOS) is detected. The influence of obesity on the pathogenesis of metabolic disorders in this category of patients remains controversialAims: to determine the frequency and structure of metabolic disorders in obese women in combination with polycystic ovary syndrome (PCOS).Materials and methods: A single-center cross-sectional sample survey of women of reproductive age was conducted. The study included clinical anthropometry with measurement of body weight, height, waist circumference (OT) and hip circumference (OB), followed by calculation of body mass index (BMI) and OT/OB ratio, and measurement of blood pressure (BP). A biochemical blood test was performed, the hormonal status was examined, and an ultrasound examination of the pelvic organs was performed.Results: A survey of 136 women of reproductive age was conducted. Group 1 included obese women without PCOS (59 patients), group 2 included obese women in combination with PCOS (45 patients), and the control group included 38 healthy women. Group 1 included obese women without PCOS (59 patients), and group 2 included obese women with PCOS (45 patients), in the control group — 38 healthy women. Among group 2 patients, dyslipidemia, visceral obesity, arterial hypertension, insulin resistance, hyperinsulinemia, and hyperuricemia were significantly more common (p<0,05). Correlations between BMI and triglycerides, testosterone and total cholesterol were found (p<0,05). Obese and PCOS patients had significantly higher levels of C-reactive protein(CRP), fibrinogen, anti-Müllerian hormone (AMH), and hepatic transaminases (p<0,05). Vitamin D deficiency was detected in 13,2% of patients, and insufficiency — in 22,7% of patients. There is a statistically significant correlation between the level of 25 (OH)D and indicators of BMI, follicle-stimulating hormone, luteinizing hormone (p<0,05), the level of AMH (p=0,008).Conclusions: A high frequency of metabolic disorders in obese women in combination with PCOS has been identified, which necessitates early screening, diagnosis and treatment of these disorders to strengthen reproductive health and prevent chronic non-communicable diseases.

Prevalence and biomarkers in metabolic syndrome

The prevalence of metabolic syndrome (MS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnostics and approaches to the prevention and treatment of this pathology. Age, lifestyle, socioeconomic status, insulin resistance (IR), dyslipidemia, obesity and genetic predisposition are factors influencing the risk of developing and progression of MS. Features of the distribution and dysfunction of adipose tissue are important factors in the development of IR, with obesity, as well as the risk of the formation of cardiometabolic diseases and MS. ­Understanding of mechanisms is linked to advances in metabolic phenotyping. Metabolic phenotyping of obese persons is important for the development of important diseases in relation to the study of the pathophysiology of metabolic disorders, the possible concomitant disease and the search for innovative strategies for the prevention and treatment of MS. The understanding of MS mechanisms is associated with advances in metabolic phenotyping. Therefore, the relevance of further study of the pathophysiological mechanisms underlying various metabolic phenotypes of MS is one of the promising areas of modern scientific research. This review summarizes the current literature data on the prevalence of MS depending on gender, age, population, area of residence, education, level of physical activity, and many other parameters. Metabolic risks of MS development are detailed. Biological markers of MS are considered. The necessity of metabolic phenotyping of MS has been shown, which may have potential therapeutic value.