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We recommend acromegaly to be ruled in all patients with characteristic changes in appearance (A3). In all patients without characteristic changes in appearance, we recommend to rule out acromegaly, if several clinical signs suspicious for acromegaly are present (B3). We recommend acromegaly to be ruled out in all patients with pituitary adenoma (B3). We recommend to rule out acromegaly in all patients with prolactin-secreting adenomas (C4). For laboratory confirmation of acromegaly, we recommend to measure serum insulin-like growth factor-1 (IGF-1, somatomedin C) level (A3). In patients without obvious clinical signs of acromegaly and/or with a moderate increase in IGF-1 levels (IGF-1 index less than 1.3), we recommend to assess the response of somatotropic hormone (GH) to hyperglycemia (GH during an oral glucose tolerance test) (B3). In all patients with biochemically confirmed acromegaly, magnetic resonance imaging of the pituitary gland with intravenous contrast is recommended to assess pituitary adenoma size, location and growth pattern (A3). We recommend to measure blood glucose and glycated hemoglobin in all patients with confirmed acromegaly (B3). We recommend to measure serum prolactin levels in all patients with acromegaly (B3).In all patients with acromegaly and pituitary adenoma, transnasal transsphenoidal adenomectomy is recommended as first-line treatment if the patient’s consent is given and there are no contraindications (A1). For all patients with acromegaly for whom neurosurgical treatment is indicated, surgical intervention is recommended in medical centers, specializing in pituitary diseases, by neurosurgeons who perform at least 50 such operations per year (A3). We recommend that morphological and immunohistochemical examination of the removed pituitary adenoma is performed in all patients with acromegaly (A3). We do not recommend routine medical therapy for acromegaly before surgery as a mean to reduce tumor size (B2).For patients with acromegaly in whom neurosurgical treatment is not indicated or ineffective or while patient awaiting for the effect of radiation therapy, we recommend medical therapy (A1). Long-acting first-generation somatostatin analogues are recommended as first-line drug therapy for acromegaly. In case of partial/complete resistance to or intolerance to somatostatin analogs, pegvisomant is recommended as a second-line medical therapy for acromegaly (A1). We recommend starting pegvisomant from a single dose of 40–80 mg per day subcutaneously, then continue injections at a starting dose of 10 or 15 mg per day with IGF-1 monitoring after 4–6 weeks and dose adjustment if necessary (B2). In patients with acromegaly and a moderate increase in IGF-1 levels, we recommend to initiate cabergoline as medical monotherapy or, if somatostatin analogs are ineffective, in combination with them (B2).In patients with acromegaly, if the disease remains active after surgical treatment, if drug treatment is unavailable, intolerable or ineffective, and repeated neurosurgical intervention is inappropriate, it is we recommend radiation therapy (A1). A multidisciplinary approach is recommended in the management of acromegaly complications (C3).

Rapid changes in the morphological characteristics of the population, which began in the middle of the last century, are due to changes in the habitat. The “obesogenic” environment that is formed in urbanized spaces contributes to physical inactivity and a hypercaloric diet, and the processes of globalization contribute to obesity in the population in all countries of the world. From the obesity epidemic declared by WHO in 1988, humanity has moved to an obesity pandemic. The presented review analyzes global and Russian trends in the development of obesity. Data on the prevalence of latent obesity and diagnostic criteria for this condition are presented. An analysis of data on the dynamics of BMI in the world and in the Russian Federation was carried out. Various options for the topography of fat deposition and their relationship with comorbid diseases are considered. The structure of the subcutaneous fat depot in the abdominal area and the influence of the outer (superficial subcutaneous abdominal adipose tissue, SSAT) and deep (deep subcutaneous abdominal adipose tissue, DSAT) layers of subcutaneous fatty tissue in the abdominal area on the risks of developing diseases are discussed. The results of assessing the diagnostic value of the T/A substitution in the FTO gene (rs9939609) for predicting the proportion of fat mass and abdominal fat deposition in adults are presented.

BACKGROUND: Recent clinical descriptions have shown that in adult patients, the cause of nondiabetic hypoglycemia (NDH) may be various genetically determined disorders of glucose metabolism or insulin synthesis/bioavailability. In this connection, in adult patients with NDH of unclear genesis, it is important to conduct a genetic study in order to search for mutations in genes associated with congenital disorders of glucose metabolism (CDGM).AIM: To evaluate the effectiveness of genetic testing to exclude CDGM in adult patients with idiopathic NDH.MATERIALS AND METHODS: Based on the analysis of the literature, a targeted panel has been developed, including 30 genes, mutations in which are associated with the following groups of diseases: 1) congenital hyperinsulinism (KCNJ11, ABCC8, GLUD1, HADH, UCP2, HNF4A, HNF1A, GCK, INSR, SLC16A1); 2) glycogen storage diseases (AGL); 3) other carbohydrate metabolism disorders (ALDOB, FBP1); 4) glycosylation defects (PMM2, ALG3, PGM1, MPI); 4) defects in fatty acid oxidation (ACADM, ETFA, ETFB, ETFDH, FLAD1, SLC25A32, SLC52A1, SLC52A2, SLC52A3); 5) disorders of ketone body metabolism (CPT1A, CPT2, HMGCL); 6) mitochondrial disorders (DLD). Twenty nine patients (n=29: with idiopathic NDH n=17 and with insulinoma n=12) aged 19 to 66 years underwent a genetic study using this custom panel.RESULTS: As a result of the examination 12 genetic variants (all heterozygous) were identified in 8 patients with idiopathic NDH (47%, 95% CI (23%; 72%)), at that two mutations were detected in three patients: in the genes AGL and HMGCL; ACADM and FLAD1, respectively; and one patient had three mutations: one mutation in the ETFA gene and two mutations in the ABCC8 gene. Frequencies of genetic variants: AGL — 18%, 95% CI (4%; 43%), ETFA — 12% (1%; 36%), HMGCL — 6% (0%; 29%), ALDOB — 6% (0%; 29%), CPT1A — 6% (0%; 29%), ABCC8 — 6% (0%; 29%), ACADM — 6% (0%; 29%), FLAD1 — 6% (0%; 29%). 5 genetic variants (all heterozygous) were identified in 5 patients with insulinoma (42%, 95% ДИ (15%; 72%)). Frequencies of genetic variants: ABCC8 — 17%, 95% CI (2%; 48%), HNF1A — 8% (0%; 38%), ETFDH — 8% (0%; 38%), MPI — 8% (0%; 38%). We did not include benign variants in this analysis. At the same time, clinically significant variants were identified only in one patient from the group with idiopathic NDH (6%, 95% CI (0%; 29%)) in the ABCC8 gene and in one patient from the group with insulinoma (8%, 95% CI (0%; 38%)) in the same gene congenital hyperinsulinism (CHI).CONCLUSION: A panel of 30 genes has been developed, variants of which are associated with a CDGM. The results of our study confirm the possibility of detecting CDGM in adulthood, in particular CHI, and indicate the need for genetic testing, primarily in patients with idiopathic NDH.

The article discusses certain aspects of the relationship between neurological diseases and metabolic disorders that are extremely relevant in connection with the pandemic spread of obesity. The pathogenesis of damage to the nervous system (NS) is considered in detail. The influence of the main metabolic factors on the development of cerebrovascular diseases (CVD), incl. neuroinflammation, changes in hemostasis, etc. is demonstrated. The problem of the development of cognitive dysfunction against the background of obesity due to the formation of atrophic processes in brain structures is highlighted. Modern possibilities of evaluation and modulation of eating behavior due to brain stimulation using functional magnetic resonance imaging (fMRI) and navigational rhythmic transcranial magnetic stimulation (rTMS) are described.The problem of cerebrometabolic health is presented as a continuum of metabolic and cerebral disturbances. The mechanisms of interaction between the two most important systems of the body allow us to consider the changes that occur in them as an integral neuroendocrine alteration.

Androgen insensitivity syndrome is a genetic disorder characterized by complete or partial androgen insensitivity in individuals with a 46XY genotype. It is also the most common cause of disorders of sexual differentiation in patients with a 46XY karyotype. This condition is caused by a defect in the androgen receptor gene (AR), leading to abnormal development of male genitalia, impaired formation of male secondary sexual characteristics, and phenotypic features resembling the female sex.One of the important aspects related to the management of androgen insensitivity syndrome is the necessity of preventive gonadectomy. However, the rationale for prophylactic removal of gonads remains a subject of debate. This article presents a clinical case of a 37-year-old woman with complete androgen insensitivity syndrome who, despite recommendations for gonadectomy based on suspicious MRI characteristics of the gonads, made the decision to decline surgical intervention, justifying her choice by the positive impact of gonadal hormonal activity on her external appearance and physical characteristics. This clinical case highlights the complexity of decision-making in the management of androgen insensitivity syndrome, where patient preferences and needs may play a significant role, despite potential risks and concerns surrounding the preservation of gonads.

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P

BACKGROUND: Overweight and obesity have a significant impact on the course and results of treatment of many diseases, including cancer. One of the modern types of antitumor therapy is immune checkpoint inhibitors. Taking into account the high effectiveness of immune checkpoint inhibitors for various types of tumors, it seems interesting to study the initial anthropometric data of patients and assess the possible influence of nutritional status on the development of endocrine immune-mediated adverse events.AIM: To compare groups of patients with different starting body mass index (BMI) before the first administration of the immune checkpoint inhibitors drug and analyze the risk of developing endocrine immune-mediated adverse events in the future.MATERIALS AND METHODS: The single-center study included 172 patients who were recommended antitumor therapy immune checkpoint inhibitors at the N.N. Blokhin National Medical Research Center of Oncology and Moscow City Oncology Hospital №62 in 2020–2022. Measurement of height and body weight with further calculation of BMI was carried out before the first administration of the drug immune checkpoint inhibitors.Depending on the subsequent occurrence of immune-mediated adverse events, patients were divided into groups: those with developed immune-mediated adverse events (any, cutaneous, thyroid) and those without immune-mediated adverse events (any, cutaneous, thyroid).RESULTS: According to the results of our study, in 38 patients (37.3%) out of 102, for whom data on the presence/absence of any immune-mediated adverse events were obtained, the following were recorded: thyropathies (n=13, 12.7%), skin lesions (n=13, 12.7%), gastrointestinal toxicity (n=7, 6.9%), hepatotoxicity (n=4, 3.9%), hypophysitis (n=2, 2%), nephritis (n=2, 2%), diabetes mellitus (DM) (n=1, 1%), hematological toxicity (n=1, 1%), pneumonitis (n=1, 1%), Guillain-Barré syndrome (n=1, 1%). At the same time, in most patients only one immune-mediated adverse event was encountered (n=31, 81.6%), two immune-mediated adverse events were detected significantly less frequently (n=7, 18.4%).When conducting a comparative analysis of groups of patients with developed immune-mediated adverse events, including dermatological ones, or their absence, a statistical trend in differences in BMI was obtained. Using ROC analysis, a BMI cut-off point was determined equal to 28.16 kg/m² for all immune-mediated adverse events and 25.39 kg/m² for skin immune-mediated adverse events, below which, contrary to the available data, the risk of developing immune-mediated adverse events increased, but the diagnostic sensitivity (DS) and diagnostic specificity (DS) turned out to be low.CONCLUSION: We identified a statistical trend in the risk of developing immune-mediated adverse events (primarily dermatological) with a lower BMI before the start of antitumor immunotherapy immune checkpoint inhibitors. More research is required to find a more reliable relationship.

BACKGROUND: Artificial hypoglycemia (ArH) is a decrease of blood glucose levels less than 3 mmol/l due to the deliberate use of hypoglycemic drugs by a patient outside of medical appointments. Timely diagnosis of this kind of hypoglycemia avoids unnecessary numerous examinations and hospitalizations. However, the detection of ArH still remains an extremely difficult task for both the healthcare facility and the attending physician. The foreign literature describes cases of successful detection of deliberate intake of oral hypoglycemic drugs (OHD) using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). Thus, it is relevant to develop and validate a method for determining OHD using HPLC-MS/MS.AIM: To optimize the diagnosis of ArH due to the use of OHD.MATERIALS AND METHODS: A total of 92 patients were examined. The development of the HPLC-MS/MS method for the detection of the studied OHD (sOHD; n=1-glibenclamide, n=1-gliquidone, n=1-gliclazide, n=1-glimepiride, n=1-glipizide, n=1-nateglinide and n=1-repaglinide) in the blood was carried out in a group of patients with diabetes mellitus type 2 (n=7) who received sOHD, and a group of conditionally healthy people who did not receive any medications (n= 7). To validate the method, the determination of sOHD substances was carried out on groups of patients with hyperinsulinemic nondiabetic hypoglycemia (NDH) of unknown origin (n=11) and with insulinoma (n=67).RESULTS: In the study of blood samples by HPLC-MS/MS in the group of patients with diabetes mellitus type 2, was confirmed in 100% of the cases the use of the drug that the patient received, in the group of conditionally healthy — sOHD were not detected. A false positive result was not obtained in any conditionally healthy and in any patient with insulinoma. ArH was diagnosed in 5 out of 11 patients in the group with hyperinsulinemic NDH of unknown origin, the method identified sOHD glibenclamide and gliclazide in the patients’ blood samples. In the remaining 6 patients of this group, examinations were continued and other causes of NDH were diagnosed. The sensitivity of the method was 100% [74%; 100%], specificity — 100% [95%; 100%].CONCLUSION: The HPLC-MS/MS method has high diagnostic accuracy in the detection and identification of sOHD (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in blood samples of patients receiving these drugs. Currently, due to the low availability of the method, this study is advisable to use in patients with hyperinsulinemic hypoglycemia with negative results of first-line insulinoma imaging methods (computed tomography with contrast enhancement, ultrasound and magnetic resonance imaging of the abdominal cavity).

A corrigendum on "Androgen insensitivity syndrome: preventive gonadectomy, "pros" and "cons"" (Obesity and metabolism by Еvgenia A. Starostina, Nadezhda V. Frolkova, Seidbike M. Seidova, Elena G. Przhiyalkovskaya, Nadezhda M. Platonova (2024). Obesity and metabolism. 2024;21(1):85-91. doi: https://doi.org/10.14341/omet13024On page 87 the sentence “In addition, testosterone preparations are used to treat infertility in patients with a mild form of STF [3]” was removed. Added paragraph “Birnbaum W et al. conducted a multicenter, double-blind, randomized, crossover study in three university medical centers and three specialized hospitals in Germany. In this study, patients aged 18-54 years with karyotype 46,XY, genetically confirmed CAIS, removed gonads, were treated with either estradiol drugs at a dose of 1.5 mg/day for 6 months, followed by a transition to testosterone 50 mg /day for 6 months (sequence A), or testosterone preparations 50 mg/day for 6 months, followed by a transition to estradiol 1.5 mg/day for 6 months (sequence B).In the study, testosterone was well tolerated and as safe as estrogen. The authors suggested that testosterone may be an ­alternative replacement therapy for CAIS, particularly for patients with reduced sexual function."A new source has been added in the reference list section under No. 30: “Birnbaum W, Marshall L, Werner R, et al. Oestrogen versus androgen in hormone-replacement therapy for complete androgen insensitivity syndrome: a multicentre, randomized, double-dummy, double-blind crossover trial. Lancet Diabetes Endocrinol. 2018;6(10):771-780. doi:10.1016/S2213-8587(18)30197-9.”The authors regret the error. The original version of the article has been replaced.

BACKGROUND: It is known that insulinoma in approximately 5% of cases is associated with multiple endocrine neoplasia type 1 syndrome (MEN1), in which the prognosis and management tactics of patients have been developed in detail. The diagnosis of MEN1 often does not require genetic confirmation, since the syndrome has a typical clinical picture. At the same time, a combination of this tumor with other hereditary syndromes is found in the literature, which are characterized by the presence of malignant neoplasms of various localizations, primary multiple lesions, hormonal and other disorders. Thus, it is relevant to search for the genetic causes that cause the development of insulinoma, in addition to MEN1.AIM: to evaluate the frequency of detection of genetic causes of the development of insulin-producing tumors of the pancreas, in addition to MEN1; to analyze the phenotypic characteristics of patients with such tumors.MATERIALS AND METHODS: Based on the analysis of literature for the period up to 2020, a panel has been developed that includes coding regions of 10 genes (MEN1, VHL, TSC1, TSC2, KRAS, YY1, CDKN2A, MLH1, ADCY1, CACNA2D2) involved in the development of insulinoma. In 32 patients diagnosed with insulinoma, verified by pathomorphological examination, with the absence of clinical and/or genetic data indicating MEN1 syndrome, a panel of genes was sequenced with subsequent analysis of the identified genetic variants and phenotypic data obtained from the medical records of patients. In one patient, an additional molecular genetic study of the «Endom» panel was performed, revealing genetic variants of coding regions of 377 genes associated with endocrine diseases.RESULTS: In 8 patients (25%, 95% CI (11%; 43%)), 9 variants of mutations were identified that were not classified as benign, at that two mutations in the TSC2 gene were detected in one patient. Frequencies of genetic variants: TSC2 — 13%, 95% CI (4%; 29%), MEN1 — 6% (1%; 21%), MLH1 — 3% (0%;16%), CDKN2A/P16INK4A — 3% (0%;16%). When comparing patients with the identified mutation, with the exception of benign (n=8), and patients without mutation or with a benign mutation (n=24), there were no differences in the Grade (degree of differentiation), Ki67 proliferation index, frequency of concomitant tumors, burdened history, multiple pancreatic lesions or recurrence of insulinoma, however, patients with germinal mutation were found at the level of statistical trend to be younger at the manifestation of insulinoma and to have bigger tumors. In a patient who underwent an additional molecular genetic study using the new «Endome» panel, previously undescribed gene variants (APC and KIF1B) associated with various sporadic tumors, including endocrine ones, were identified.CONCLUSION: A panel of 10 genes has been developed, mutations of which are associated with insulinoma. A relatively high incidence of genetically determined insulinoma was determined (25% of cases), in half of cases — against the background of tuberous sclerosis. We consider it relevant to evaluate the effectiveness of genetic testing for patients with insulinoma. We believe that, first of all, patients with a high risk of hereditary pathology should be examined: with the manifestation of the disease at a young age and with a large tumor. The identification of a genetic mutation will make it possible to determine the prognosis of the disease, optimize the monitoring algorithm in order to timely identify concomitant diseases-components of the hereditary syndrome, and conduct genetic counseling of the family.

Currently, increasing evidence shows the mutual influence of aldosterone and adipose tissue. Aldosterone excess has been reported in patients with obesity and metabolic syndrome. Aldosterone has a direct effect on adipose tissue increasing anabolic activity and expression of mineralocorticoid receptors. In turn, excessive activation of MCR leads to stimulation of adipogenesis and an increase in the volume of adipose tissue. Aldosterone excess can be considered an independent cardiovascular risk factor that affects such processes as cardiac fibrosis, nephrosclerosis, and arteriosclerosis. There is convincing evidence of higher prevalence and severity of impaired glucose homeostasis and lipid metabolism disorders among patients with primary hyperaldosteronism. Similar pathological changes are also observed in patients with obesity and metabolic syndrome. This review presents scientific data on the metabolic effects of aldosterone, in particular its effect on adipose tissue function, glucose and lipid metabolism. Treatment with mineralocorticoid receptor antagonists may provide substantial benefit in the management of metabolic syndrome, contribute to the stabilisation of glucose and lipid metabolism, improve clinical status of patients with cardiovascular diseases and reduce the risk of complications. However, available evidence from the conducted studies is not sufficient to justify introduction of such therapy into clinical practice.

BACKGROUND: Pituitary adenomas are the third most common intracranial neoplasm. Clinical significance is determined by the nature of growth and hormonal activity, leading to disruption of various parts of metabolism. Medical registries are a valuable tool for assessing clinical and epidemiological parameters and obtaining data on real-life clinical practice.AIM: To analyze the epidemiological and clinical characteristics of four pituitary disorders in Russian Hypothalamic and Pituitary Tumor Registry (OGGO): acromegaly, Cushing’s disease, prolactin-secreting and non-functioning pituitary adenomasMATERIALS AND METHODS: The object of the study is the database of the OGGO registry, which includes 84 regions of the Russian Federation, as of 01/01/2023.RESULTS: The maximum prevalence of acromegaly in the Russian Federation was noted in Karelia (9.48/100 thousand) and Chuvash Republic (10.8/100 thousand) and in Tyumen region (8.9/100 thousand). The incidence of acromegaly in 2021 was 0.6/1 million population. The maximum prevalence of Cushing’s disease is observed in Karelia Republic (2.33/100 thousand), Chukotka (2.01/100 thousand), Kirov (1.79/100 thousand) and Tver region ( 1.79/100 thousand). The incidence of Cushing’s disease in 2021 was 0.1/1 million population. The maximum prevalence of prolactinomas is observed Karelia (13.33/100 thousand) and Chuvash Republic (12.35/100 thousand) and in Voronezh region (8.66/100 thousand). The incidence of prolactin-secreting adenomas in 2021 was 0.6/1 million population. The maximum prevalence of non-functioning pituitary adenomas is observed in the Karelia (15.08/100 thousand), Voronezh region (8.82/100 thousand), Tyumen region (8.11/100 thousand) and Sakha/Yakutia Republic (7.56 /100 thousand). The incidence of non-functioning pituitary adenomas in 2021 was 0.3/1 million population. The median age for acromegaly was 63.6 [53.2;71.5], for Cushing’s disease 49.2 [38.8;60.8], for prolactin-secreting adenomas 47.5 [38.3;59.7], for patients with non-functioning pituitary adenomas — 58.4 [43.8;67.9] . At the time of the last visit, remission was observed in 42.7% of patients with acromegaly, 62.5% with Cushing’s disease, 39.7% with prolactinomas and 76.6% of patients with non-active adenomas.CONCLUSION: The OGGO registry is a valuable tool for assessing epidemiological, clinical data and treatments used. At the same time, the quality of the analysis directly depends on the quality and completeness of the entered data. Further research in the field of epidemiology of endocrinopathies should be aimed at improving the quality and ease of data entry, which will allow obtaining the most complete patient characterization.

Increasing life expectancy and, as a consequence, a large number of comorbidities lead to a multitude of medications prescribed by physicians of different specialties. Patients with obesity and carbohydrate metabolism disorders, especially with type 2 diabetes mellitus (DM2), are at particular risk of polypragmasy, which is associated with the use of potentially nonrecommended medications. Prescribing errors can cause significant harm to the patient’s health and increase the risk of rehospitalization and healthcare costs. Identification of probably not recommended drugs in this category of patients will improve understanding of prevalence and risk factors of their use, develop strategies to prevent and limit the burden of taking inappropriate drugs and promote development of personalized and patient-oriented treatment options. Tools exist to assess potentially inappropriate therapy (PIT) in the elderly and new tools and criteria are often created. However, they are not specifically aimed at people with obesity and carbohydrate metabolism disorders. Thus, these criteria usually include only a few items related to DM2. Consequently, there is a clear need for a modern tool that can be used to address PIT specifically in older adults with obesity and carbohydrate metabolism disorders.

Hyperandrogenism is the most prevalent cause of menstrual cycle abnormalities and infertility in women. Here, we present a case of a 32-year-old woman with a 7-year history of menstrual irregularity and infertility. Laboratory test results revealed elevated 17-hydroxyprogesterone, progesterone 21-deoxycortisol. Abdominal computed tomography found a 3,9х2,9х2,6 cm left adrenal tumor. Non-classic congenital adrenal hyperplasia was diagnosed initially, however, treatment with supraphysiological doses of dexamethasone proved ineffective and progesterone and 17-hydroxyprogesterone levels remained high. Genetic testing revealed no 21-hydroxylase deficiency. Laparoscopic adrenalectomy was performed with subsequent pathological report being compatible with an adrenal cortical adenoma. 17-hydroxyprogesterone, progesterone 21-deoxycortisol levels returned to the normal range postoperatively and the patient’s menstrual cycle normalized without additional medication. Steroid metabolites producing adenomas are also extremely rare with only a few cases found in patients without previous CAH diagnosis. When a patient with clinically and biochemically diagnosed NCCAH demonstrate no typical features and shows poor response to steroid therapy, the patient should receive multisteroid LC–MS/MS assay for glucocorticoids and androgens, adrenal and ovarian imaging and undergo CYP21A2 gene mutation analysis.

Rituximab is a chimeric (mouse and human) monoclonal antibody against B-lymphocytes (CD20). This drug is widely used in rheumatology in the treatment of rheumatoid arthritis, Sjogren’s syndrome, some systemic connective tissue diseases and vasculitis, as well as in hematology in lymphoproliferative diseases. Administration of rituximab leads to depletion of B-lymphocytes through various mechanisms, including antibody-dependent and complementdependent cytotoxic effects, as well as the regulation of apoptosis. Considering the mechanism of autoimmune damage in Graves’ disease, an autoimmune thyroid disease accompanied by thyrotoxicosis and endocrine ophthalmopathy (an autoimmune lesion of the accessory apparatus of the eye), the use of rituximab may be effective in these diseases. The review considers the currently available results of studies on the use of various doses of rituximab in these diseases.

Hypogonadism in men can cause the development of obesity, primarily abdominal, associated with high cardio-metabolic risks. Chronic obesity, in turn, almost inevitably leads to the manifestation of hypogonadism, which requires treatment and aggravates cardiovascular risks. Testosterone therapy, prescribed according to indications, has a significant positive effect not only on a man’s sexual function, but also on body weight, carbohydrate and lipid metabolism, bone metabolism and the emotional component of men’s health. The improvement of many metabolic parameters in men with verified hypogonadism occurs against the background of fairly long-term testosterone therapy. Hypogonadism and visceral obesity are now considered as components of the metabolic syndrome, mutually burden each other and require a comprehensive therapeutic approach.

BACKGROUND: The steadily increasing number of people with obesity requires the development of simple and accurate methodological approaches to assess the absolute and relative amount of body fat mass. The body adiposity index (BAI) is one of the indices proposed to assess the body fat percentage. However, the comparison analysis of common methods, i.e., of bio-electrical impedance analysis and ultrasound scanning, and BAI was not performed for the Russian population.AIM: Comparison analysis of the body fat percentage estimates by bio-electrical impedance analysis, ultrasound scanning, and body adiposity index in the group of adult male and females.MATERIALS AND METHODS: An examination of healthy males and females from Moscow was conducted. Height, weight, waist and hip circumferences were measured. The body fat percentage was obtained by bio-electrical impedance analysis — BIA (ABC-02 Medas), ultrasound scanning — US (BodyMetrixTM, IntelaMetrix), and body adiposity index.RESULTS: 263 females and 134 males aged 18 to 73 years participated in the study. Correlation coefficients between BAI values and the body fat percentage obtained by BIA and US were 0.749 and 0.763 (p

BACKGROUND: Insulinoma is a pancreatic neuroendocrine tumor that manifests by impaired carbohydrate metabolism with the development of hypoglycemic syndrome. The instrumental methods used at the present stage do not always make it possible to identify a tumor; moreover, the data obtained often contradict each other. Thus, the search for new possibilities of visualization of insulinoma is relevant.AIM: Evaluation of diagnostic effectiveness of scintigraphy with single-photon emission computed tomography combined with X-ray computed tomography (SPECT/CT) with 99mTc-Tectrotide for insulinoma in a Russian cohort of patients.MATERIALS AND METHODS: A single-centre (Endocrinology Research Centre of the Ministry of Health of the Russia), experimental, single-stage, controlled study. In the years 2017–2021 patients with pancreatic insulinoma (group 1) and hyperinsulinemic hypoglycemia of a different genesis (group 2) with negative or contradictory results of the 1st line imaging methods (ultrasound, magnetic resonance imaging (MRI), computed tomography (CT)) were included. All participants underwent the whole-body scintigraphy and low-dose SPECT/CT with 99mTc-Tectrotide (500–900 MBq). The studies were performed on a tomograph of the SPECT/GE Discovery NM/CT 670 using low-energy high-resolution collimators (LEHR) in the «whole body» mode.RESULTS: In the group 1 (n=21), according to the results of a pathomorphological study, the presence of 26 insulin-producing tumors was confirmed. Group 2 included 9 patients. According to the SPECT/CT with 99mTc-Tectrotide, 14 tumors were diagnosed in group 1 out of 26 insulin-producing tumors of the pancreas, and negative results were obtained in group 2 in 100% of cases. Thus, the sensitivity and specificity of the method were: 54%, 95% CI [33%; 73%] and 100%, 95% CI [68%; 100%], respectively.CONCLUSION: SPECT/CT with 99mTc-Tectrotide can detect insulinoma in 54% of cases with negative or contradictory results of 1st-line imaging methods (ultrasound, MRI, CT). This study can be effectively used as an alternative to SPECT/CT with 111In-octreotide, as a 2nd-line method for topical search for an insulin-producing pancreatic tumor.

Aim: present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points. Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion. Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.

Current therapeutic approaches to the treatment of endocrine ophthalmopathy (EOP) are based on nonspecific immunosuppression with glucocorticosteroids (GCs) and radiation therapy of the eye orbits. However, some patients exhibit resistance to the treatment. In a previous study, we have detected high levels of soluble cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, and the TGF-β1 cytokine in euthyroid patients with long-lasting non-treated EOP and Graves’ disease (GD). TGF-β1 level was significantly higher in the patients with EOP compared to healthy individuals, and increased with prolonged EOP duration, thus suggesting activation of the factors regulating immune system which promote suppression of the autoimmune process. The aim of this work was to study the dynamics of TGF-β1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R in the course of immunosuppressive therapy with high doses of GCs, as possible predictors of treatment efficacy. The study included 49 patients (98 eye orbits) with GD of euthyroid state and subclinical thyrotoxicosis, and the persons with EOP in active phase, who had not previously treatment for EOP. Concentrations of TGF-β1 cytokine, sTNFα-RI and sTNFα-R2, sIL-2R, antibodies to the thyroid-stimulating hormone receptor (rTSH), free fractions of thyroxine (fT4) and triiodothyronine (fT3), TSH in blood serum were determined in blood serum. Ultrasound examination of the thyroid gland (ultrasound of the thyroid gland), multi-layer computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits were also performed. The patients were administered immunosuppressive therapy with high doses of HCs (methylprednisolone) in the course of pulse therapy, at a standard dosage of 4500-8000 mg, taking into account the severity and activity of the EOP clinical manifestations. The examination was carried out 3, 6, 12 months after starting the treatment. 3 and 6 months after the GC administration, more than 30% of patients remained resistant to treatment. The levels of TGF-β1 did not change significantly in the patients with positive EOP dynamics. In the patients resistant to GC treatment, the level of TGF-β1 was significantly decreased compared with patients who showed positive clinical dynamics. The level of sNFR1 and sNFaR2 did not change significantly. There were no significant differences in the levels of antibodies to rTSH, thyroid hormones in the patients resistant to GC treatment and with positive dynamics.Immunosuppressive therapy with high-dose of methylprednisolone in pulse therapy regimen showed high efficacy and good tolerability, while some patients remain resistant to treatment. Lower levels of TGF-β1 cytokine at initial time and during the treatment allow usage of TGF-β1 levels as a biomarker of the activity of the process, treatment efficiency, and prognosis of the disease. Activation of TGF-β1, a fibroblast growth factor, may contribute to the development of fibrosis, strabismus, and diplopia.

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

AIMS. Study of the dynamics of brain activity using functional MRI (fMRI) in obese patients treated with sibutramine (Reduxine®).MATERIALS AND METHODS. The study enrolled patients with a body mass index (BMI) ≥30 kg/m2 . All participants underwent initial brain fMRI mapping. The obesity cohort was treated with sibutramine at a dose of 10 or 15 mg per day for 3 months. After treatment patients with obesity underwent a second fMRI mapping to assess changes against the initial mapping.RESULTS. The study included: 30 patients (86,7% women) with mean age of 31 [27.25; 36] years, mean body weight (BW) - 106 [95.75; 121.75] kg, mean BMI 37.4 [33.55; 41.9] kg/m2 , mean waist circumference (WC) - 109 [100; 114.75] cm. The most marked activation volume (via fMRI) was observed in patients with obesity (before treatment) in the visual cortex (occipital lobes). After 3 months of treatment with sibutramine, 80% of patients lose ≥5% of BW. Mean BW decrease was -7.2 [-13.46; -5.37] kg, BMI decrease — -7.2 [-13.49; -5.34] кг/м2 , WC decrease — -6.9 [-11.88; -4.03] см, p

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.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by a defect in one of the enzymes or transport proteins involved in the cortisol synthesis in the adrenal cortex. The most common form of CAH, which occurs in more than 90% of cases, is a 21-hydroxylase enzyme deficiency. The latter is subdivided into nonclassical and classic (salt-losing and virilizing) forms. The prevalence of classic forms of 21-hydroxylase deficiency ranges from 1: 14,000 to 1:18,000 live births worldwide. According to the data of neonatal screening in the Russian Federation, the prevalence of the disease in some regions ranges from 1: 5000 to 1: 12000, in the country as a whole - 1: 9638 live newborns. The non-classical form of CAH occurs more often - from 1: 500 to 1: 1000 among the general population. In second place is the hypertensive form of CAH - a deficiency of 11β-hydroxylase, which, according to the literature, occurs in about 1 per 100,000 newborns. These clinical guidelines were compiled by a professional community of narrow specialists, approved by the expert council of the Ministry of Health of the Russian Federation, and updated the previous version published in 2016. The clinical guidelines are based on systematic reviews, meta-analyses and original articles, and scientific work on this issue in the Russian Federation and other countries. The purpose of this document is to provide clinicians with the most up-to-date, evidence-based guidelines for the CAH diagnosis and treatment

Coding of the causes of death of patients with diabetes mellitus (DM) in the Russian Federation is one of the long-discussed problems, due to the comorbidity of diabetes and cardiovascular diseases (CVD) and a number of contradictions in the key regulatory documents regulating the statistics of mortality in this category of patients, which acquires particular relevance in the context of the coronavirus pandemic, due to its negative impact on the outcomes of the course of COVID-19 and mortality risks. In pursuance of the decisions of the Minutes of the meeting of the working group under the project committee of the National Project «Health» on identifying patterns in the formation of mortality rates of the population dated January 20, 2021 No. 1, chaired by Deputy Prime Minister of the Russian Federation T.A. Golikova, experts of two directions - endocrinology and pathological anatomy, prepared a Draft of agreed recommendations on the Rules for coding the causes of death of patients with diabetes, causing the greatest problems in terms of the use of ICD-10 when choosing the initial cause of death, including in the case of death from CVD and COVID-19.

Introduction. In Russian Federation, there are no comprehensive studies assessing the quality of life and risk factors for vitamin D deficiency and insufficiency, taking into account its status in different geographic latitudes.Aim. To assess the quality of life and risk factors for vitamin D deficiency and insufficiency among the population living in the regions of the Russian Federation located at latitudes from 45 ° to 70 °.Materials and methods. The first stage of the Russian multicenter non-interventional registry study using the “cross-sectional” method was carried out from March 2020 to May 2020.Results and discussion. According to the results of the correlation analysis, qualitative and quantitative factors were identified, presumably being risk factors for vitamin D deficiency and deficiency. Qualitative risk factors include: education; alcohol consumption; being in direct sunlight for more than 30 minutes a day; visit to the solarium; using sunscreen; drinking coffee; taking medications (not vitamin-mineral complexes). Quantitative factors include: visits to specialists (total per year); smoking (duration, years); exercise for more than 30 minutes a day, once a week; being in direct sunlight for more than 30 minutes a day.Conclusion. A wide range of risk factors for vitamin D deficiency dictates the need for their further study to clarify the category of persons who are shown targeted biochemical screening with subsequent drug correction.

Pheochromocytoma/paraganglioma is a neuroendocrine tumor of chromaffin and nonchromaffin cells of the autonomic nervous system, in most cases localized in the medullary layer of the adrenal gland. Its development is often associated with genetic predisposition. More than 30% of adult patients have genetically determined PCC/PG. In the last decade, many genes predisposing to the manifestation of PCC/PG have been found: RET, VHL, NF1, SDHB, SDHC, SDHD, SDHA, SDHAF2, TMEM127, MAH, KIF1BP, PHD2, EGLN1, FH, H-RAS, IDH, SLC25A11, MDH2. Mutation of the oncosuppressor genes TMEM127 and EGLN1, which regulate the level of factors induced by HIF hypoxia, is extremely rare in patients with PCC/PG, and has not been described at all in combination with pancreatic tumor. To date, data on the clinical manifestations of these gene mutations are limited. Accumulating clinical data on patients with identified genetic alterations is important for predicting the course of the disease, clarifying the malignant potential and stratifying the risk of developing comorbid pathology. We present the clinical case of a 62-year-old patient with PCC/PG and pancreatic tumor in whom a previously undescribed combination of TMEM127 c.99G > A (p.S33S) and EGLN1 c.515C > T (p.A172V) gene variants was found.

Introduction. One of the objectives of weight loss in obesity is to prevent metabolic disorders associated with it. An important component in the maintenance of the achieved results is a change of eating behavior.Goal: to study the effect of liraglutide 3.0 mg on the dynamics of metabolic parameters and eating behavior in patients with obesity. Materials and methods. The study enrolled 42 obese patients in whom anthropometric parameters, metabolic parameters, and eating behavior were assessed with Dutch Eating Behavior Questionnaire (DEBQ). Patients were divided into 2 groups, one of which received liraglutide 3.0 mg with lifestyle modification for 3 months. The other group was recommended to receive only lifestyle modification. The participants were re-examined after 3 months.Results and discussion. in the liraglutide group in addition to a significant decrease in body weight, BMI and waist circumference, there was a statistical trend toward lower glucose, insulin and HOMA-IR levels. When comparing the dynamics of parameters between the groups, Д body weight, BMI and glucose in the liraglutide group were significantly superior. In reassessment of eating behavior after 3 months of treatment, no statistically significant differences were found with the initial severity of restrictive, emotional, and/or external types in both groups and, despite a more pronounced decrease in body weight in the liraglutide group, between them.Conclusions: Three months of isolated lifestyle modification and/or its combination with liraglutide 3.0 mg is not sufficient to make a lasting change in eating behavior. However, considering that obesity is a chronic and relapsing disease, the need for eating behavior correction remains relevant to prevent disease recurrence. This substantiates the need for more long-term intervention in obesity, including drug therapy.

Riedel's thyroiditis is a rare disease characterized by chronic fibrosis. Clinical performance of this disease is dense stony goiter, which can poorly be displaced during palpation. The overgrowth of the goiter can lead to the development of compression syndrome. To diagnose we need to made fine needle biopsy and made the final diagnose according to its results or according to the morphological description of the postoperative material. An important step in the diagnosis of Riedel's thyroiditis is the determination of serum IgG and IgG4 to exclude an IgG4-associated disease. Treatment of this disease includes drug therapy, which is based on glucocorticosteroids administration or surgical treatment when develops compression syndrome. This article presents a clinical case of a patient with Riedel's thyroiditis; the main complaints were associated with the growth of goiter and the development of compression syndrome. In this regard, patient underwent surgery on the thyroid gland, and after this we get final diagnose. Due to feeling unwell, drug therapy with glucocorticosteroids was prescribed, against the background of which we noted a positive trend.

Clinical guidelines have long been one of the working tools of the modern doctor, helping him quickly navigate the most effective proven methods of treatment and prevention of various diseases, and also to adapt these methods to the specific tasks of their patients and to achieve maximum personalization of treatment. Clinical practice guidelines are drawn up by professional non-profit associations and are approved by the Scientific Council of the Ministry of Health of the Russian Federation, while often one recommendation is prepared by two or even three associations. The peculiarity of the recommendations offered to your attention is that not only endocrinologists, but also therapists, cardiologists, gynecologists, gastroenterologists, and experts of many other specialties are involved in the prevention and treatment of obesity. The Multidisciplinary Working Group presents this a project in a multidisciplinary journal to bring together the efforts of several professional associations that associated with the need to pay attention not only to obesity itself but also to comorbid conditions. We are looking forward to constructive criticism and a comprehensive discussion of the problem on the pages of our journal.

Rationale: In Russia, assessment of anti-P450c21 antibodies (AB) in the diagnosis of autoimmune adrenal insufficiency (AAI) has not been commonly used, and the disease screening has not been implemented.Aims: 1) To determine the sensitivity and specificity of anti-P450c21 AB determination in the AAI diagnosis; 2) To estimate the prevalence of anti-P450c21 AB carriage in patients without AAI.Materials and methods: Anti-P450c21 AB were assessed in 40 patients (group 1) with manifest AAI; 171 patients without established diagnosis of AAI, including 113 subjects with autoimmune thyroid disorders or type 1 diabetes mellitus (AID, group 2); 25 carriers of AB markers of thyroid AID and/or type 1 diabetes mellitus without any target organ dysfunctions (group 3); 33 patients with non-autoimmune endocrine disorders (group 4), and 25 healthy individuals (group 5).Results: Determination of anti-P450c21 AB for the diagnosis of AAI had 95% sensitivity, with specificity of 100%, predictive value of a positive result of 100%, and predictive value of a negative result 92.6%. Anti-P450c21 AB were inversely correlated with the duration of glucocorticoid replacement therapy (r=-0.222, p

Adrenal insufficiency (AI) is a syndrome caused by disturbance in the synthesis and secretion of hormones of the adrenal cortex, which ensure the vital activity, energy and water-salt homeostasis. The widest hormonal deficiency is observed in primary hypocorticism, when the synthesis of not only glucocorticoids (GC) and adrenal androgens, but also mineralocorticoids is disrupted. Lifelong replacement therapy with GCs for this pathology may be associated with a risk of bone loss and osteoporosis. However, at present, there are no clear guidelines for diagnosis of bone condition, including and bone mineral density (BMD) monitoring during treatment with GCs in patients with AI. This review summarizes collected data on the key pathogenetic links of glucocorticoid-induced osteoporosis, incidence of decreased BMD and fractures in patients with AI. In this review factors that influence bone metabolism in this cohort of patients are considered: the type and the dose of prescribed GCs, the type (primary, secondary, HH in congenital adrenal cortex dysfunction) and the duration of AI, age, gender, and the presence of concomitant endocrine disorders (hypogonadism, growth hormone (GH) deficiency). In addition, the review presents data on the effect of adrenal androgen replacement therapy and recombinant GH therapy on bone metabolism in secondary AI.

The nature of human nutrition has become increasingly important as an effective element in the prevention and treatment of many pathologies, especially obesity, type 2 diabetes and cardiovascular diseases. High protein diets are some of the most popular eating patterns and the Dukan diet has taken the lead in popularity among the diets of this type. An increase of protein in the diet is effective in reducing body weight, primarily due to the loss of adipose tissue, without a significant effect on muscle mass. Another advantage of a high-protein diet is earlier and longer satiety compared to other diets, which makes it comfortable for use. Besides obesity, high protein diets are presumably effective for treating such diseases as nonalcoholic fatty liver disease, diabetes mellitus and cardiovascular diseases However, despite the important advantages, this nutritional model is not universal and is contraindicated in patients with diseases of liver, kidneys and osteoporosis. Besides, the prolonged use of a high protein diet may increase the risks of urolithiasis and reduced mineral bone density even for healthy individuals. Thus, the increase in the proportion of protein in the diet should take place exclusively under the supervision of a physician.

Gravess disease is a common part of Autoimmune polyglandular syndrome (APS) and among thyroid autoimmune disorders is usually preceded the onset of the syndrome. Aim.The aim of this study was to determine the frequency of occurrence of APS type 2, 3 among patients with Graves disease. Materials and methods.Sera of 94 patients with Gravess disease, 116 patients with APS 24 types and 80 healthy subjects were screened for 21-OH Ab, insulin-Ab (IAA), Islet Cell-Ab (ICA), glutamic acid decarboxylase-Ab (GADA), protein tyrosine phosphatase-Ab (IA2), Zinc Transporter 8-Ab (ZnT8), Anti-gliadin-Ab (IgA+IgG) (AGA), Anti-transglutaminase-Ab (IgA+IgG) (Anti-tTG), Anti-parietal cell-Ab (APCA), Intrinsic Factor-Ab (IF), Rheumatoid factor (RF), Anti Ovarian Antibodies (AOA). Serum cortisol, fasting plasma glucose levels were measured. Results.The presence of Addisons disease and the onset of Type 1 DM was not determined among Graves disease patients. None of the patients with Graves disease and in the healthy control group had 21-OH-antibodies detected. The frequency of 21-OH-Ab was 4.2% in APS type 3 (p=0.07) and 91.6% in APS type 2, 4 (p0.001). The prevalence of diabetes-associated autoantibodies was 20.2% among Gravess disease patients against 8.75% in healthy subjects control group (p0.05); OR 2.64; 95% CI 1.056.66 and 30.2% in APS of adults (DM 1 negative group) (p=0.18). The prevalence of APCA-markers of autoimmune gastritis was 31.9% in Gravess disease, 48.3% in APS 24 types (p=0.01); OR 1.99; 95% CI 1.183.51, and 12.5% in control group (p0.01); OR 3.28; 95% CI 1.497.24. There were no significant differences in the frequency of occurrence of IF-Ab and RF-Ab in the groups. The frequency of AGA and ATA was 28.7% in Graves disease, 36.2% in APS types 24 (p=0.3), 10% in the control group ((р0.01); OR 3.63; 95% CI 1.548.54. Graves disease patients with risk of developing APS type 3 (positive diabetes-associated and other autoantibodies) had relatives with autoimmune diseases in 57.5% of cases (p=0.05); OR 2.18; 95% CI 1.034.63. Conclusion.Graves disease patients are at high risk for future development of APS 3 type, especially those with inheritance for autoimmune diseases. Screening for the immunological markers, pathognomonic for coexisting autoimmune diseases in such patients with Graves disease, as well as in patients with APS type 3, should be done regularly.

Radioactive iodine, flying out of the destroyed reactor of the Chernobyl nuclear power plant, like a corona virus quickly spread throughout Europe. Iodine deficiency in the regions of Ukraine, Belarus and Russia adjacent to nuclear power plants became a factor in increased uptake of radioactive iodine by the thyroid gland in children and after 5 years led to an epidemic of thyroid cancer. Optimal iodine intake could become a kind of vaccination, which sharply reduces the risk of developing thyroid cancer, as has happened after the accident at the Fukushima nuclear power plant in Japan. Endemic goiter was eliminated 50 years ago, but returned to the country in the early 1990s after the collapse of iodized salt production and has not been eliminated to this day due to the lack of a legislative framework for mandatory salt iodization. The actual average consumption of iodine by residents of Russia is from 40 to 80 mcg per day, which is 23 times less than the recommended norm. Mild and moderate iodine deficiency was detected throughout the Russian Federation, and it is more typical for the the rural population. The iodine deficiency has the greatest negative effect on the psychomotor development of the child during the critical period the first 1000 days of life from the moment of conception to the end of the second year of life. According to WHO, over the past 20 years, iodine deficiency has been eliminated in 115 countries of the world, and the number of iodine-deficient countries has dropped to 25, but Russia is still among them. We believe that after the COVID-19 pandemic, it will no longer be necessary to prove the need for effective support for the prevention of both infectious and non-infectious diseases, and the declared preventive direction of Russian medicine will indeed become such.

Vitiligo is a common polygenic autoimmune disease in which the foci of depigmentation are formed on the skin and/or mucous membranes as a result of the death of melanocytes. There are several hypotheses for the pathogenesis of the disease, the leading role among them is played the autoimmune hypothesis. This review summarizes the available literature data on the prevalence and structure of comorbid endocrine autoimmune pathology in vitiligo patients. In most studies conducted in Europe, America and Asia the prevalence of autoimmune thyroid diseases (including autoimmune thyroiditis and Graves disease), diabetes mellitus and autoimmune adrenal insufficiency was higher in vitiligo patients than in the general population. The results of some studies indicate a frequent association of vitiligo with autoimmune polyglandular syndromes. In the structure of comorbid pathology the highest prevalence was in autoimmune thyroid diseases. A number of studies have established a higher prevalence of autoimmune endocrine diseases in women, as well as in nonsegmental vitiligo patients and in cases of family history of vitiligo and/or other autoimmune diseases. In addition, it was shown that the prevalence of endocrine diseases increases with increasing area of depigmentation. The data obtained justify the advisability of conducting a timely examination of vitiligo patients with the aim of early detection of comorbid diseases and the appointment of appropriate treatment. Further studies are needed to investigate the effect of the identified associations on the course of vitiligo and comorbid endocrinopathies, as well as the effectiveness of therapy and the quality of life of patients.

The prevalence of hypothyroidism in the population is high. The frequency of manifest hypothyroidism in the world, according to various data, is 0.2–2.0%, subclinical one – up to 10% for women and up to 3% for men, and in the older age group (over 70 years) reaches 14%, with the majority of cases of hypothyroidism accounted for primary hypothyroidism. Thus, a doctor of any specialty in his practice is likely to meet a patient with hypothyroidism: both with the established diagnosis, and face the need for differential diagnosis of various pathological conditions with hypothyroidism. This article presents a classification of hypothyroidism based on etiological aspects, describes the clinical picture of the disease, pays special attention to the so-called «masks» of hypothyroidism, which, in our view, can be useful for a doctor of any specialty, provides available methods for diagnosing this syndrome (special attention is paid to laboratory methods), as well as the goals and principles of treatment, highlights the need to monitor laboratory indicators in dynamics against the background of treatment. In addition, the features of correction of hypothyroidism during pregnancy are given. The article presents the peculiarities of selecting drug doses depending on the patient’s age and comorbidity. The distinctive feature and the purpose of this article, from our point of view, is its potential benefits not only for endocrinologists, but also for other health professionals.

Triiodothyronine (T3, 3,5,3’-L-triiodothyronine) is a thyroid hormone (thyroid), the secretion of which is carried out directly both by the gland (to a lesser extent) and outside it (the main amount; as a result of peripheral deiodination of thyroxine (T4)). Getting into the nuclei of cells, T3 interacts with specific nuclear receptors of target tissues, which determines its biological activity. This interaction leads to the activation of transcription of a number of genes.In the pituitary gland and peripheral tissues, the action of thyroid hormones is modulated by local deiodinases, which convert T4 to more active T3, the molecular effects of which in individual tissues depend on subtypes of T3 receptors and their interaction with other ligands, coactivators and corepressors, as well as on the activation or repression of specific genes.The reason for the lack of T3 production is primarily a deficiency of iodine in the diet, less often, a defect in the genes encoding the proteins that are involved in T3 biosynthesis. As a result of the low intake of iodide in the body, the so-called adaptive mechanism is activated, which consists in increasing the proportion of synthesized T3, which increases the metabolic efficiency of thyroid homones. With a deficiency in the diet of such a trace element as selenium, the conversion of T4 to T3 is reduced.Thyroid hormones play a vital role in the regulation of homeostasis and the metabolic rate of cells and tissues of humans and mammals. They are necessary for physical and mental development. Their insufficient production at the stage of formation of the internal organs of the fetus and in childhood can lead to various pathologies, primarily to pathology of the central nervous system, and as a result, growth retardation and mental retardation. In adulthood, hypothyroidism leads to a decrease in metabolism, memory impairment, depressive disorders, impaired fertility. Many discussions and ambiguous conclusions have been obtained regarding combination drugs (sodium levothyroxine + lyothironon) for the treatment of hypothyroidism. This article will examine the metabolic effects of T3, the thyroid hormone with the highest activity.

Hypoglycemic syndrome (HGS) is a significant decrease glucose in blood, manifested by neurological symptoms, and stopped by the introduction of glucose. Among the many causes of HGS the special place is taken by the factitious hypoglycemia, as one of the variants of Munchausen syndrome. Hypoglycemia in such cases is achieved by the intentional introduction of hypoglycemic drugs. The most commonly used medications are sulfonylurea derivatives, which are affordable, inexpensive and legal. The close collaboration of clinicians with the laboratory service plays a key role in the diagnosis of factitious hypoglycemia. Since the results of biochemical and hormonal analyzes in patients with hypoglycemia due to reception of oral hypoglycemic medications and pancreatogenous HGS are identical, the only way to differentiate these conditions is by detection of insulin secretagogue substances in the blood (or urine).The determination of oral hypoglycemic medications in cases of suspicion of artificial reception is not implemented in Russia. Factitious hypoglycemia in most cases is the diagnosis of exclusion, and its confirmation if often based on detection of medications among the personal effects of patient. This is a significant difficulty given the ethical standards. However, since 2018 we conduct in our Centre the determination of 7 oral hypoglycemic medications (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in patient’s blood using the liquid chromatography–tandem mass spectrometry (LC-MS). This article presents a clinical case of a patient without diabetes mellitus taking glibenclamide and detection of this drug using highly selective LC-MS.

Background: In the Russian Federation, newborn screening comprises thyroid stimulating hormone determination to exclude primary congenital hypothyroidism. Screening is carried out throughout Russia. Neonatal TSH can be used to assess iodine deficiency and monitor iodine prevention programs.Objective: To assess and compare official statistical data on congenital hypothyroidism, the prevalence of hypothyroidism and iodine deficiency syndrome in children, as well as urinary iodine in the Russian regions.Materials and methods: The level of neonatal TSH was determined in 97.69% of children born in the Russian Federation in 2017. This article represents the results on the prevalence of hypothyroidism in the regions with various iodine availability. The correlation analysis was used to assess the relationship of CH incidence in newborns and iodine availability.Results: The calculated correlation coefficient, which was 0.2, reflects a weak relationship between the degree of iodine deficiency in the region and the number of newborns diagnosed with congenital hypothyroidism.Conclusions: In the Russian Federation, a law on universal salt iodization does not exist, and many regions are still in conditions of moderate or severe iodine deficiency. To assess the iodine status in these particular regions, we could use the results of newborn TSH screening

The mechanisms of mutual influence of fat tissue and the hypothalamo-pituitary-adrenal (HPA) axis include the regulation of the metabolism of adipocytes by adrenal cortex hormones, on the one part, and the effect of adipocytes and adipocytokines on secretion, metabolism and action of steroid hormones in target cells - on the other part.Glucocorticoids contribute to the differentiation of preadipocytes into mature adipocytes; brown fat tissue transforms into white under the effect of GC. Mineralocorticoids are also involved in the process of adipocyte differentiation, regulate adipokine expression, and induce oxidative stress in fat tissue. There is evidence that suggest that circulating dehydroepiandrosterone sulfate (DHEAS), obesity, insulin sensitivity are associated with the presence of cardiovascular diseases.Orexigenic neuropeptides and inflammatory mediators, which trigger the synthesis of corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nuclei, are considered as possible mechanisms of (HPA) axis activation in obesity. Expression of 1ip-hydroxysteroid dehydrogenase type 1 (11P-HSD1) in fat tissue and the formation of cortisol from cortisone at the tissue level can be considered as one of the factors involved in development of insulin resistance. The autocrine and paracrine regulatory effect of these hormones on adipocyte function is the consequence of aldosterone production and aromatization of androgens by fat tissue.

Insulinoma is the most common functioning tumor of the pancreas. Approximately 5% of its cases are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), caused by mutation in the MEN1 gene. MEN1 can be manifested by pituitary and parathyroid adenomas, pancreatic neuroendocrine tumors, tumors of the thyroid gland, adrenals, intestine, carcinoids of lungs and other organs. However, in 5–10% of the patients with clinical manifestation of this syndrome, MEN1 mutations cannot be identified. Moreover, the disease can be caused by various abnormalities (mutations, polymorphisms, etc.) in other genes. More than 30 genes, associated with insulin-producing pancreatic tumors, have been described in the literature. With a known germinal mutation, the prognosis and management of patients with insulinoma can be determined by the hereditary disease with which the tumor is associated. The article emphasizes the need to search for new genetic markers that predispose to the development of insulinoma. The necessity of extended genetic testing of patients with insulinomas is discussed, primarily of young patients with multifocal lesions, family history and associated disorders.

The steadily growing interest in studying of endocrine genetics is driven not only by the search for new pathologies but also by the most pressing need to develop methods for early diagnosis, treatment and management of patients. Though 20% of all the patients with von Hippel-Lindau syndrome do not have a family history of the disease; a genetic basis is a natural characteristic of the disease and determinates a phenotype. Despite the nonaggressive course, in general, a relative unpredictability of the syndrome signs onset and the lack of regular monitoring can increase the risk of surgery complications and cause a disability at a young age. The presented clinical case shows the need for a multidisciplinary approach to management of the patients with von Hippel-Lindau syndrome.

Nowadays obesity is a major health problem worldwide. Surgery is the most promising treatment for morbid obesity. There are two types of bariatric procedures, one to reduce the food intake volume and the other to limit the absorption of nutrients. Despite the indisputable advantages of bariatric surgery for weight loss, it is necessary to remember the potential risk of severe complications, such as hypoglycemic syndrome at 2 to 3 hours after ingestion of rapidly absorbable carbohydrates manifested by adrenergic and neuroglycopenic symptoms. According to the literature, the prevalence of post-bariatric postprandial hyperinsulinemic hypoglycemia (PHH) varies from 10% to 75%. PHH in post-bariatric patients should be differentiated from the syndrome of non-insulinoma pancreatogenic hypoglycemia and from insulinoma; however, these diseases are described also in patients after bariatric surgery.The mechanisms of PHH as an outcome of shunting bariatric procedures are currently not fully clear. According to the recent studies, incretin hypersecretion in response to the accelerated flow of carbohydrates into the small intestine plays a leading role in the inappropriate excess production of insulin by the pancreas. In addition, there are hypotheses on a slower normalization of insulin production during more rapid bodyweight decrease and regression of insulin resistance, the role of alpha-cell dysfunction, disturbed negative feedback between insulin and ghrelin, compensatory hyperplasia and hypertrophy of the remaining enterocytes (including L-cells), changes in gut microflora, bile acids level and composition. A number of other mechanisms have also been proposed that require further studies.

The causes of postprandial hyperinsulinemic hypoglycemia (PHH) in patients who have undergone an upper gastrointestinal tract surgery are still a matter of debate in the scientific community. Low postoperative body mass index, high postprandial beta-cell activity before the surgery, and younger age are all have been associated with higher PHH risk. It is hypothesized that the insulin-like growth factor-1 increases the tissue sensitivity to insulin and indirectly promotes the development of hypoglycemia. An increase in postprandial secretion of enteropancreatic hormones is still considered to be the main reason for PHH manifestation; however, a particular contribution has been ascribed to glycentin, which could be used as a marker of PHH risk in the future.At present, there are no clinical guidelines for the diagnosis of PHH. Undoubtedly, the first step in this direction should be the collection of the disease history. The provocative tests have been proposed for the detection of PHH. Today, the 72-hour fast test is still the gold standard in the diagnosis of hypoglycemia. However, most post-bariatric patients do not have fasting hypoglycemia, and insulinoma is extremely rare in this patient category. The use of a prolonged oral glucose tolerance test as the main method is associated with a risk of a false diagnosis, because about 12% of healthy individuals may have their glycemic levels at below 2.8 mmol/l. The mixed meal test has not been validated yet. The best results in the assessment of glucose variability have been obtained with “real time” continuous glucose monitoring the interstitial fluid for several days.The goal of PHH treatment is to reduce the stimulated insulin secretion. First of all, patients are advised to eat small meals consisting of carbohydrates with a low glycemic index in combination with proteins and lipids, with high fiber content. Should the nutritional modification be ineffective, it is possible to prescribe medical treatment, such as acarbose or somatostatin analogs. Diazoxide and slow calcium channel blockers can be used as the third line of therapy. A recent study has suggested that exogenous agonists of glucagon-like peptide-1 (GLP-1) receptors by stronger bonds with receptors, compared to those with endogenous GLP-1, could enhance glucagon response to hypoglycemia, thereby stabilizing glucose levels. In severe refractory PHH, reconstructive surgery and gastric banding are to be considered. If the expected decrease in insulin hypersecretion by reconstructive surgery is not achieved, partial or complete pancreatectomy remains the only possible approach to prevent hypoglycemia. However, due to the small number and short duration of the studies, effectiveness and safety of these techniques for PHH treatment have not yet been proven.

The topical diagnosis of insulinoma continues to be an actual problem of modern medicine due to low detection rate of the tumor (about 75%) and inconsistent data on its localization when using various methods of visualization (more than in 50% of cases), as well as the lack of a single diagnostic algorithm. In the clinical practice, many different imaging assessments are conducted, including those with the administration of contrast agents and associated with radiation load, as well as invasive studies, associated with risk of various complications, high costs and duration of the examination. Thus, the search for highly sensitive and safe methods of topical diagnosis of the insulin-producing pancreatic tumor seems relevant. In the presented clinical case, the diagnosis of insulinoma is verified by diffusion-weighted magnetic resonance imaging (DW-MRI). It is an accurate and non-invasive method that does not involve exposure to ionizing radiation and does not require any administration of contrast agents. This technology, based on microstructural pathological changes, allows to identify small tumors and to make a differential diagnosis of benign and malignant neoplasms. However, at present the experience of DW-MRI use for the diagnosis of an insulin-producing neuroendocrine tumor is limited. Evaluation of its effectiveness in a large patient cohort would be necessary to assess the prospects for its introduction into clinical practice.

Nonalcoholic fatty liver disease (NAFLD) – a common chronic disease of the liver, the main feature of which is the accumulation of fat in hepatocytes, is not related to alcohol abuse. NAFLD is associated with obesity, especially abdominal, metabolic syndrome and various metabolic markers of risk for cardiovascular disease and type 2 diabetes, which affects the incidence, prognosis and life expectancy of patients with obesity. This lecture describes the main causes of the disease, its pathogenesis, clinical presentation, diagnosis and treatment.

Obesity is a chronic disease associated with cardiometabolic risk factors, primarily cardiovascular diseases and type 2 diabetes mellitus. In 2016,Russiaregistered a new drug for treating obese patients liraglutide 3.0 mg, which is an analogue of human glucagon-like peptide-1. Given the urgency of the problem, we present a clinical case that shows the efficacy of therapy with liraglutide 3.0 mg daily in a patient with obesity, and its effect on metabolic risk factors.

Hypoglycemic syndrome is a symptom complex that results from low blood sugar levels. In the endocrinologist practice, an insulinoma that is a small tumor in the pancreas that produces an excess amount of insulin is regarded as the main cause of hypoglycemia in patients without diabetes mellitus. Various molecular and genetic disorders develop in the insulinoma tissue, that lead to a change in the secretion of insulin and its precursors.There is often a situation when it is not possible to establish the cause of lowering blood glucose levels. In such cases, the development of hypoglycemia can result from various genetically determined enzyme, autoimmune and receptor disorders that cause a change in glucose metabolism or the synthesis/bioactivity of insulin. In the mild course of such congenital diseases, hypoglycemic conditions may first manifest in adulthood.The review describes various genetic predictors (mutations) that play a decisive role in the development of enzyme, autoimmune, receptor and proliferative disorders and, as a consequence, hypoglycemia.

Obesity is a chronic disease associated with cardiometabolic risk factors of cardiovascular diseases and type 2 diabetes. In 2016, in Russia a new drug was registered for the treatment of patients with adiposity - liraglutide 3.0 mg, which is an analog of human glucagonoma peptide-1. The study purpose: to study the efficacy of liraglutide 3.0 mg/day and its impact on cardiometabolic risk factors in patients with obesity. We examined 30 patients aged 25-59 with obesity without diabetes. Patients received therapy with liraglutide 3.0 mg/day for 3 months. The examination included measurement of anthropometric parameters, blood sampling with the estimation of the parameters of lipid and carbohydrate metabolism.Results: after 3 months of treatment with liraglutide 3.0 mg a significant improvement of anthropometric parameters was observed: reduction of weight, BMI and waist circumference and a significant improvement in parameters of metabolic comorbidities.Conclusions: complex therapy with use of liraglutide 3.0 mg per day for 3 months is effective for therapy of obesity and correction of obesity-associated cardiometabolic disturbances.