Agreement between bioimpedance analysis and ultrasound scanning in body composition assessment.

OBJECTIVES: This study aimed at evaluating the agreement between bioelectrical impedance analysis (BIA) using ABC-02 Medas and A-mode ultrasound (AUS) using BodyMetrix™ BX2000 for fat mass (FM), fat free mass (FFM), and body fat percentage (%BF) in females. METHODS: The cross-sectional, single-center, observational study was performed in 206 female subjects aged 18-67 years. The examination program included measurements of body height and weight along with waist, hip circumferences, and body composition analysis. The measurements were performed by ultrasound scanner and bioimpedance analyzer. RESULTS: We found that 20.9% of women were obese based on BMI (≥30 kg/m2), which was significantly lower when using a criterion based on body fat percentage (%BF ≥ 30%) measured with US (53.4%, p = .0056) or BIA (54.8%, p = .0051). At the group level, both methods were found interchangeable and showed practically negligible differences (0.1% for %BF, 0.5 kg for FM, and 0.4 kg for FFM). Agreement analysis conducted in the whole sample revealed a low level of agreement in estimating %BF (CCC = 0.72 0.77 0.82) and FFM (CCC = 0.81 0.84 0.86), and medium level of agreement in estimating FM (CCC = 0.91 0.93 0.94). The level of agreement in estimating %BF and FFM was improved to the medium level with the use of newly generated prediction equations. CONCLUSION: Thus, the proposed equations can be used for conversion of body composition results obtained by AUS into the BIA data.

Clinical Case Report of Non-Diabetic Hypoglycemia Due to a Combination of Germline Mutations in the MEN1 and ABCC8 Genes.

INTRODUCTION: Non-diabetic hypoglycemia (NDH) is a collective term including the multiple causes of hypoglycemic syndrome not due to diabetes mellitus. NDH may result from insulinoma, IGF-2-omas, hypocorticism, Hirata's disease, genital disorders of glucose metabolism, etc. One of the most common causes of NDH faced by an endocrinologist is insulinoma, which in turn can be part of the hereditary syndrome of multiple endocrine neoplasia type 1 (MEN1). Congenital disorders of glucose metabolism in adult patients, on the contrary, are diagnosed extremely rarely, since they usually manifest in childhood. This article presents a unique clinical case of a patient with NDH and genetically verified MEN1 in combination with congenital hyperinsulinism due to an ABCC8 gene mutation. CASE REPORT: A 43-year-old patient with hypoglycemic symptoms from childhood is presented, in whom multiple pancreatic tumors and fluctuations in glycemia from 38.7 mg/dL to 329.7 mg/dL (2.15 to 18.3 mmol/L) were detected in adulthood, but a mild course of hypoglycemic syndrome was noted. Numerous examinations that were performed to establish an accurate diagnosis are described, signs that served as a reason for expanding the complex of studies are indicated, possible pathogenetic mechanisms of the mild course of hypoglycemic syndrome and hyperglycemic conditions are discussed. CONCLUSION: This case report is original and highlights that we must always remain intolerant of the inexplicable. Conducting an extended gene study can help perform a correct diagnosis in complex cases.

Diagnostic Accuracy of Methods for Detection of Antibodies against Type I Interferons in Patients with Endocrine Disorders.

Autoantibodies against type 1 interferons (IFN-I) are a highly specific marker for type 1 autoimmune polyglandular syndrome (APS-1). Moreover, determination of antibodies to omega-interferon (IFN-ω) and alpha2-interferon (IFN-α2) allows a short-term diagnosis in patients with isolated and atypical forms of APS-1. In this study, a comparison of three different methods, namely multiplex microarray-based, cell-based and enzyme-linked immunosorbent assays for detection of antibodies against omega-interferon and alpha2-interferon, was carried out. A total of 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine disorders, and healthy individuals were analyzed. In the APS-1 patient cohort (n = 18), there was good agreement between the results of anti-IFN-I antibody tests performed by three methods, with 100% specificity and sensitivity for microarray-based assay. Although only the cell-based assay can determine the neutralizing activity of autoantibodies, the microarray-based assay can serve as a highly specific and sensitive screening test to identify anti-IFN-I antibody positive patients.

Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the 'Red Zone' of the Endocrinology Research Center, Moscow, Russia.

The aim of this study was to assess the correlations of clinical features of patients with moderate and severe courses of COVID-19, comorbidity (endocrine, autoimmune, cardiovascular, oncological, and pulmonary diseases), and alleles of the HLA class II system genes. One hundred COVID-19 patients hospitalized in the Endocrinology Research Centre, Moscow, Russia, were analyzed for age, gender, smoking, comorbidity, and invasive mechanical ventilation. Computer tomography was used to assess the severity of the disease. HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles were identified in samples from 100 patients and samples from 327 randomly selected individuals collected in the prepandemic period (control group). There was no association of gender, age, weight, body mass index, smoking, and comorbidity with the severity of COVID-19. Allele DQB1*06:02-8 was more common in patients (p < 0.00005), and DQB1*06:01 and DQB1*05:03 were more common in the control group (p < 0.00005, and p = 0.0011, respectively). DQB1*06:02-8 can probably be considered as predisposing to moderate and severe COVID-19, and DQB1*06:01 can be considered as protective. No association of these alleles with comorbidity was found. Our results suggest that carriers of predisposing alleles, with cardiovascular and non-autoimmune endocrine diseases, should take more stringent preventive measures, and if infected, a more aggressive COVID-19 treatment strategy should be used.

Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism.

BACKGROUND: Hypoglycemic syndrome is a potentially life-threatening condition that can lead to the disruption of brain and internal organ functions, and in severe cases to irreparable consequences or death. Factitious hypoglycemia (FH) is the deliberate use of insulin preparations or oral hypoglycemic drugs with the aim of lowering blood glucose levels into the pathologically-hypoglycemic range. Deliberate administration of insulin analogs may be difficult to prove because they might not have epitopes or containing low affinity epitopes that are the targets of antibodies used in particular assay kits. CASE PRESENTATION: A 34 years old woman was admitted to the Endocrinology Research Centre in September 2021 with a diagnosis of hypothyroidism and diabetes mellitus. Upon admission she complained of high glycemia indexes up to a maximum of 34 mmol/l ( 612 mg/dl), high TSH and low free T4 ( fT4) concentrations, despite reporting regular levothyroxine administration at a dose of 200 mcg per day. Under nursing supervision, her fT4 was rapidly normalized suggesting non-compliance as the cause of low thyroid hormone milieu. Glycemic fluctuations from 33 to 2.1 mmol/l (594 to 38 mg/dl) according to glucometer measurements were observed against the background of Lis-Pro insulin therapy, while no hyperglycemia was registered in venous blood and in the interstitial fluid concomitantly with the values found by glucometer. It was assumed that the patient's fingers were intentionally contaminated with glucose solution. Factitious hypo- and hyperglycemia were suspected. During yet another episode of hypoglycemia (1.86 mmol/L, 33 mg/dl) venous blood was drawn. Low to low-normal insulin and C-peptide values were found: 2.2 µU/ml (Roche kit) and 1.18 ng/ml, respectively. Therefore, insulin concentration in the same sample was re-tested with another kit (Abbott) and a significantly elevated value of 89.9 µU/ml was detected. Based on these results, FH was confirmed due to exogenous administration of an insulin analog undetectable by the Roche kit. CONCLUSION: This clinical example illustrates to draw attention to multiple manipulations employed by subjects with Munchhausen Syndrome. In addition, this diagnosis may be further complicated by the laboratory use of immunoassay kits incapable of detecting some insulin analogs.

Microarray-Based Detection of Antibodies against SARS-CoV-2 Proteins, Common Respiratory Viruses and Type I Interferons.

A microarray-based assay to detect IgG and IgM antibodies against betacoronaviruses (SARS-CoV-2, SARS, MERS, OC43, and HKU1), other respiratory viruses and type I interferons (IFN-Is) was developed. This multiplex assay was applied to track antibody cross-reactivity due to previous contact with similar viruses and to identify antibodies against IFN-Is as the markers for severe COVID-19. In total, 278 serum samples from convalescent plasma donors, COVID-19 patients in the intensive care unit (ICU) and patients who recovered from mild/moderate COVID-19, vaccine recipients, prepandemic and pandemic patients with autoimmune endocrine disorders, and a heterogeneous prepandemic cohort including healthy individuals and chronically ill patients were analyzed. The anti-SARS-CoV-2 microarray results agreed well with the ELISA results. Regarding ICU patients, autoantibodies against IFN-Is were detected in 10.5% of samples, and 10.5% of samples were found to simultaneously contain IgM antibodies against more than two different viruses. Cross-reactivity between IgG against the SARS-CoV-2 nucleocapsid and IgG against the OC43 and HKU1 spike proteins was observed, resulting in positive signals for the SARS-CoV-2 nucleocapsid in prepandemic samples from patients with autoimmune endocrine disorders. The presence of IgG against the SARS-CoV-2 nucleocapsid in the absence of IgG against the SARS-CoV-2 spike RBD should be interpreted with caution.

Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course.

CONTEXT: Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed. OBJECTIVE: This work aims to find a novel genetic predictor of APS. METHODS: We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1. RESULTS: In patient B, we identified inherited compound mutations as a novel combination of the c.769C > T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient. CONCLUSION: Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE-mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS.

Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes.

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.

Search for Genetic Predictors of Adult Autoimmune Polyendocrine Syndrome in Monozygotic Twins.

Autoimmune polyendocrine syndromes (APS) are a heterogeneous group of diseases characterized by the presence of autoimmune dysfunction of 2 or more endocrine glands and other non-endocrine organs. The components of the syndrome can manifest throughout life: in childhood-APS type 1 (the juvenile type) and in adulthood-APS type 2, 3, and 4 (the adult types). Adult types of APS are more common in clinical practice. It is a polygenic disease associated with abnormalities in genes encoding key regulatory proteins of the major histocompatibility complex (MHC). The search of for candidate genes responsible for mutations in adult APS is continuing. Genetic predisposition is insufficient for the manifestation of the APS of adults, since the penetrance of the disease, even among monozygotic twins, does not approach 100% (30-70%). The article presents the case of isolated Addison's disease and APS type 2 in monozygotic twins with a revealed compound heterozygosity in the candidate gene VTCN1.

Clinical Case of Surreptitious Hypoglycemia Due to Deliberate Insulin Analog Administration.

Hypoglycemic syndrome is a life-threatening condition that can lead to hypoglycemic coma and death. Surreptitious hypoglycemic syndrome is the deliberate use of insulin preparations or oral hypoglycemic drugs aimed to reduce blood glucose level. If human insulin is injected, high level of immunoreactive insulin (IRI) and low level of C-peptide at the moment of hypoglycemia are always detected. However, the fact of deliberate administration of insulin analogs is difficult to prove. In these cases if insulin kit test with low cross-reactivity with insulin analogs is used, the low levels of IRI and C-peptide will be suspected. Some experts suggest the presence of cross reactivity with analogs of insulin in a number of commercial kits, which makes it possible to detect cases of surreptitious hypoglycemia. We present a clinical case of a patient with surreptitious hypoglycemia due to the administration of insulin analogs and discuss the problems of its laboratory diagnosis.

Atypical progeroid syndrome (p.E262K LMNA mutation): a rare cause of short stature and osteoporosis.

SUMMARY: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy-associated progeroid syndrome (GLPS). All of those syndromes are associated with some progeroid features, lipodystrophy and metabolic complications but vary differently depending on a particular mutation and even patients carrying the same gene variant are known to have clinical heterogeneity. We report a new 30-year-old female patient from Russia with an APS and generalized lipodystrophy (GL) due to the heterozygous de novo LMNA p.E262K mutation and compare her clinical and metabolic features to those of other described patients with APS. Despite many health issues, short stature, skeletal problems, GL and late diagnosis of APS, our patient seems to be relatively metabolically healthy for her age when compared to previously described patients with APS. LEARNING POINTS: Atypical progeroid syndromes (APS) are rare and heterogenic with different age of onset and degree of metabolic disorders, which makes this diagnosis very challenging for clinicians and may be missed until the adulthood. The clinical picture of the APS depends on a particular mutation in the LMNA gene, but may vary even between the patients with the same mutation. The APS due to a heterozygous LMNA p.E262K mutation, which we report in this patient, seems to have association with the generalized lipodystrophy, short stature and osteoporosis, but otherwise, it seems to cause relatively mild metabolic complications by the age of 30. The patients with APS and lipodystrophy syndromes require a personalized and multidisciplinary approach, and so they should be referred to highly specialized reference-centres for diagnostics and treatment as early as possible. Because of the high heterogeneity of such a rare disease as APS, every patient's description is noteworthy for a better understanding of this challenging syndrome, including the analysis of genotype-phenotype correlations.

[Corrigendum: hypoglycemic syndrome in patients with monoclonal gammopathy [problems of endocrinology 2020;65(6) doi: 10.14341/probl12266]].

The article «Hypoglycemic syndrome in patients with monoclonal gammopathy» published by Solovyev MV, Yukina MY, Troshina EA in Problems of Endocrinology 2020;65(6) (doi: 10.14341/probl12266) contains wrong data in «Conflict of interests» section. Correct information is: «Manuscript preparation and publication was supported by the Russian Science Foundation (project No. 17-75-30035). The information given in the article about the sources of funding should not have any significant effect on the perception of information by readers and / or interpretation of the data presented. The authors regret the incorrect information in a previously published article.

[Oxidative stress and its role in the development of autoimmune thyroid diseases].

A large number of socially significant diseases is accompanied with oxidative stress and carry with tissue damage. Free radicals play a crucial role in the development of these diseases. Similar processes occur under the influence of ionizing radiation and bacterial infections. Recently, was indicated the significant role of oxidative stress in the development of autoimmune thyroiditis. It is assumed that the synthesis of thyroid hormones depends on the concentration of H2O2, which, due to its high toxicity, must be in strict accordance with the activity of antioxidant systems. Many biochemically negative processes occur on the apical membrane of the thyrocyte, which allows limiting the effect of free radicals and avoid cell destruction. However, in pathological conditions, enzymatic systems are disturbed and their components become abnormally activated in the cytoplasm, and it is leads to functional and morphological disorders. A deeper understanding of oxidative stress and its role in the development of autoimmune thyroiditis can contribute to the identification of new methods for its assessment, the expansion of therapeutic ranges for this disease. This review discusses oxidative stress, which is the accumulation of active damaging agents (free radicals, prooxidants, reactive oxygen species) that initiate cell damage and lead to the development of various pathological conditions.

[The value of central regulators of the immune response in the development of autoimmune thyroid diseases].

The specific relationship between the endocrine and immune systems is represented by a numerous number of factors and mechanisms that form the structure and ensure the function of each of the two systems. For example, immunocompetent cells can produce immunologically active substances, as well as some hormones. On the other hand, immune cells are available to the effects of endogenous hormones. Currently, the so-called cross-regulation of endocrine and immune mechanisms in an equilibrium of pro-and anti-inflammatory responses has not been sufficiently studied. Among other autoimmune lesions, autoimmune thyreopathy occupies a significant place. The development of an autoimmune lesion of the thyroid gland is a complex process, which is the result of the interaction of infiltrating lymphocyte and thyrocyte tissue that can express a wide range of molecules involved in the immune response. Immunological and immunogenetic factors play a major role in the pathogenesis of autoimmune thyroid diseases, such as autoimmune thyroiditis and Graves disease. Despite the fact that more than 100 years have passed since the first description of autoimmune thyroiditis and Graves disease has been known for many centuries, the mechanisms of these pathologies are still not fully understood.

[Hypoglycemic syndrome in patients with monoclonal gammopathy].

One of the reasons for the development of hypoglycemia is the synthesis of autoimmune antibodies to insulin or its receptor – insulin autoimmune syndrome (IAS). The largest number of cases of this syndrome is described in the Japanese population. The antibodies to insulin are most often polyclonal immunoglobulins. In monoclonal gammopathy of undetermined significance and multiple myeloma secreted pathological monoclonal immunoglobulin may have an affinity for human insulin, which induces the development of IAS. The prolonged persistence of episodes of hypoglycemia of unknown origin requires the exclusion of the monoclonal nature of secreted antibodies to insulin. Often the presence of pathological secretion for a long time is not recognized due to the absence of other manifestations of the disease. The manifestation of gammopathy is represented by a wide range of symptoms and syndromes requiring the collaboration of doctors of various specialties. This review summarizes the literature on IAS in patients with monoclonal gammopathy, whose disease debuted from episodes of spontaneous hypoglycemia. When hemoblastosis remission is achieved (when the secretion of the pathological protein is minimal or not determined), the glucose, insulin, and antibodies levels of insulin normalize, and when multiple myeloma recurs, episodes of hypoglycemia resume. The onset of the disease from the IAS can be considered as a new criterion for symptomatic multiple myeloma, dictating the need for the initiation of specific therapy.

[Immunoendocrinology - issues and challenges of today].

The World Health Organization has declared this century to be the century of autoimmune diseases. These include a whole spectrum of endocrine disorders, with type 1 diabetes mellitus, thyropathies, autoimmune polyglandular syndromes (APS), adrenal insufficiency and others, are among the most severe chronic non-infectious diseases in humans. Both the etiology and pathogenesis of autoimmune endocrinopathies are being actively studied, the concepts of the manifestation and progression of these diseases have already been formed, data on the genetic predisposition to one or another autoimmune damage to the endocrine system organs have been obtained, prenatal diagnosis of APD is being actively developed and introduced, attempts are being made to edit the genome in order to prevent their development. Despite this, there are still enough «white spots¼ in understanding the processes of induction and implementation of the mechanisms of autoimmunity in a particular person. The close connection of the immune and endocrine systems is obvious. The key question is: what is still primary, a genetic predisposition to «breakdown¼ of the immune system, leading to the development of an autoimmune endocrine disease, or some external influence that can cause direct damage to the endocrine organ (up to its destruction), leading in the end to the breakdown of immune tolerance and the launch of a cascade of autoimmune processes that aggravate an endocrine disorder? Modern advances not only in endocrinology, but also in immunology, molecular genetics, cell biology, etc. are absolutely necessary to clarify the relationship of immuno-inflammatory, hormonal and metabolic disorders in the pathogenesis of endocrine diseases at the cellular and molecular level and to develop new methods of prevention, early diagnosis, predicting the course and effectiveness of therapy for autoimmune endocrinopathies.

[The role of HLA genes: from autoimmune diseases to COVID-19].

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II - to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm¼ in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

[Instrumental and laboratory parameters of myocardial function in adult patients with autoimmune polyglandular syndrome type 2, 3].

BACKGRAUND: Аutoimmune polyglandular syndrome (APS) it is characterized by damage to two or more endocrine glands, which eventually results in the hormonal failure. Some clinical studies describe the development of myocardial lesion in the setting of combined autoimmune endocrine pathology. In Russia the myocardial condition in adult patients with APS types 2 and 3 was examined for the first time. AIM: To evaluate the structure and functional state of the myocardium according to magnetic resonance imaging (MRI), to analyze changes in the spectrum of specific antiheart autoantibodies and markers of heart lesion in patients with APS types 2 and 3. MATERIALS AND METHODS: 50 patients with APS types 2, 3 were studied. 45 of them were performed with delayed contrast heart MRI. All 50 patients were tested for IgG antibodies to heart muscle antigens by indirect enzymatic immunoassay (EIA), for troponin I and natriuretic peptide by chemiluminescence immunoassay (CLIA), for creatine phosphokinase (CPK) by NAC (N - acetyl-L-cysteine), and for C-reactive protein (CRP) by immunoturbidimetry. RESULTS: According to the results of heart MRI (n=45), 91% showed signs of functional changes in the left ventricular (LV) myocardium without any signs of myocarditis. 38 of 45 examined patients had deviation of 2 or more indicants of the LV functional state, MEF 68.9±6.6%, IUMm - 86 [75; 99] g, IUSV - 60.9 [50; 66] ml, IUEDVi - 52 [44; 59] ml/m2 , IUESVi - 17 [15.3; 18] ml/m2 , IUESV - 26 [23; 31] ml, IUEDV - 85 [70; 92] ml. 1 patient (2%) had positive result according to the determination of antibodies (AB) to heart muscle antigens (AG). Troponin 1 indicants did not exceed the reference values. The level of CPK exceeded the reference values in 3 patients (6%), an increase of CRP, NT-proBNP was observed in 7 patients (14%), and a combined increase was observed in 1 case. CONCLUSIONS: We obtained MRI data indicating functional changes in the myocardium in patients with APS types 2 and 3. The autoimmune cause of these changes according to the results of determining of antiheart antibodies was not confirmed in most of the examined patients, the indicants of «damage¼ to the myocardium (troponin 1 and NT-proBNP) did not deviate from the reference range.

Insulin autoimmune syndrome.

SUMMARY: Insulin autoimmune syndrome (Hirata's disease) is a disorder caused by development of autoantibodies to insulin and manifested by hypoglycaemic syndrome. The overwhelming majority of physicians do not include it in the differential diagnosis of hypoglycaemic states because of a misconception of an extremely low prevalence of this condition. This results in unnecessary drug therapy and unjustified surgical interventions in patients that otherwise would be successfully treated conservatively. This disease is strongly associated with certain alleles of the HLA gene. In most cases, this condition develops in predisposed individuals taking drugs containing sulfhydryl groups. Formation of autoantibodies to insulin may be observed in patients with other autoimmune disorders, as well as in those with multiple myeloma or monoclonal gammopathy of undetermined significance. This paper presents the first Russian case report of insulin autoimmune syndrome in an adult patient. LEARNING POINTS: Insulin autoimmune syndrome, Hirata's disease, anti-insulin antibodies, and hypoglycaemia.

Body Weight Reduction Associated with the Sibutramine Treatment: Overall Results of the PRIMAVERA Primary Health Care Trial.

OBJECTIVE: The aim of the study was to assess the effectiveness and safety of long-term sibutramine therapy in routine clinical practice. METHODS: In total, 98,774 patients (82.3% women, 17.7% men) from 142 cities of the Russian Federation were enrolled in the PRIMAVERA program. The mean age of the patients was 39.39 ± 10.38 years, the mean body weight was 99.1 ± 14.28 kg, and the mean BMI was 35.7 ± 4.41 kg/m2. The duration of the sibutramine therapy was determined by physicians: 59.3% of patients took the drug for 6 months, the treatment course of 37.7% of patients was 12 months, and 3% of patients had treatment for 3 months. RESULTS: The BMI reduction correlated with the treatment duration: 3.4 ± 1.53 kg/m2 after 3 months of therapy, 5.4 ± 2.22 kg/m2 after 6 months, and 7.2 ± 3.07 kg/m2 after 12 months. The body weight reduction after 3, 6 and 12 months of treatment was 9.5%, 15.1%, and 19.7%, respectively. The body weight loss associated with sibutramine treatment was accompanied by a slight decrease in blood pressure and did not lead to any significant increases of the heart rate. CONCLUSIONS: The results of the PRIMAVERA study confirmed the lack of increased risk of using sibutramine in routine clinical practice in patients without underlying cardiovascular disease and low rate of adverse events.