IGF-1 and IGFBP3 as indirect markers of hepatic insulin resistance and their relation to metabolic syndrome parameters in liver steatosis patients.

Objective. The aim of the present study was to assess insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) as markers of insulin resistance in patients with prediabetes and type 2 diabetes mellitus (TDM2). Patients and Methods. This observational clinical study included 76 obese/overweight patients at the age of 45-75 years with T2DM on oral diabetic medication and ultrasonographically or by a computerized tomography (CT) diagnosed liver steatosis. Correlation analysis was performed between plasma levels of insulin, C-peptide, IGF-1, IGFBP3 and HOMA indexes on the one hand and between plasma levels of ALT, AST, triglyceride, cholesterol, and HDL cholesterol and body mass index (BMI) of patients on the other hand. In case of significant partial correlation coefficients, a multiple linear regression model with IGF-1 and IGFBP3 used as outcome variables adjusted for age and sex groups was calculated. According to these regression models, ROC curves were prepared with HOMA index=3 used as a classificator of insulin resistance. Results. Significant correlation was found between C-peptide and IGF-1 (r=0.24, p≤0.05), C-peptide and IGFBP3 (r=0.24, p≤0.05), IGFBP3 and cholesterol (r=0.22, p≤0.05) IGFBP3 and ALT (r=0.19, p≤0.05), HOMA index and triglycerides (r=0.22, p≤0.05), and HOMA index and ALT (r=0.23, p≤0.05). Significant correlation adjusted for age and gender was found between C-peptide and IGF-1 plasma levels (R2=0.20, p<0.05) with AUROC 0.685 (p≤0.01) and C-peptide and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.684 (p≤0.01). Significant correlation adjusted for age and gender was found between triglyceride and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.616 (p≤0.01). After the distribution of patients according to their IGFBP3 levels, we found a difference between the 1st and the 4th quartiles in terms of triglyceride levels. Conclusion. Our results demonstrate a fundamental role of IGF-1 and IGFBP3 in the patho-physiology of hepatic insulin resistance and suggest them as indirect indicators of the hepatic insulin resistance.

Vitamin D insufficiency is not associated with thyroid autoimmunity in Slovak women with Hashimoto´s disease.

The role of vitamin D (VD) in the etiopathogenesis of autoimmune diseases (AI) is extensively studied. However, its association with autoimmune thyroid disease (AITD) is still controversial. AIM of this study was to assess the relationship between the vitamin D status and thyroid autoimmunity in Slovak premenopausal women with newly diagnosed AITD. SUBJECTS AND METHODS: This prospective case-control study included 57 women with AITD and 41 age- and BMI-matched controls. All subjects were examined for summer and winter serum 25(OH)D, thyroid autoantibodies (a-TPO, a-TG), freeT4 and TSH concentrations. Thyroid volume was measured by ultrasound. RESULTS: There were no significant differences in serum 25(OH)D between AITD and control groups. No significant correlation between 25(OH)D and thyroid autoantibodies was found either in the whole cohort or in AITD women. The prevalence of vitamin D insufficiency was 60.31 % in AITD women and 52.5 % in the control group. No significant association between VD and thyroid autoantibodies, thyroid hormones and thyroid volume was detected in this study. CONCLUSION: Authors conclude that VD insufficiency is common in Slovak premenopausal women independently of the presence of AITD. Vitamin D insufficiency is not associated with thyroid autoimmunity in patients with early diagnosis of AITD (Tab. 3, Ref. 31). Text in PDF www.elis.sk Keywords: vitamin D, autoimmune thyroid disease, thyroid autoantibodies.

Selected biomarkers of orthostatic intolerance.

Orthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

Tumor induced osteomalacia.

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome typically caused by small endocrine tumors that secrete fibroblast growth factor 23(FGF23). TIO is clinically characterized by progressive muskuloskeletal pain, fatigue, proximal muscle weakness, and multiple fractures that lead to long-term disability. Due to the non-specific symptoms of the disease, it may take several years for them to be properly diagnosed and treated, so it is important to better inform about this rare paraneoplastic syndrome.

Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis.

OBJECTIVE: Lower production of adrenal androgens has been confirmed in females with rheumatoid arthritis (RA); however, the mechanisms of this finding are not completely understood. The aim of our study was to assess the contribution of genetic factors associated with variability of dehydroepiandrosterone sulfate (DHEAS) levels to lower DHEAS in female RA patients. METHODS: 448 RA and 648 healthy controls were genotyped for single-nucleotide polymorphisms (SNPs) in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306), and ARPC1A (rs740160). Serum DHEAS concentrations were measured in 112 RA patients and 91 healthy women. RESULTS: The allele frequencies in DHEAS-related loci were similar in RA and controls. RA patients had significantly lower serum DHEAS concentrations compared to healthy women. The cumulative number of alleles associated with lower DHEAS within genes ZKSCAN5, SULT2A1, HHEX, and ARPC1A present in each individual negatively correlated with DHEAS levels in RA patients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RA patients but not in the control group. CONCLUSION: Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.

[The prevalence of type 2 diabetes mellitus in patients with autoimmune thyroiditis in hypothyroid stadium]. / Výskyt diabetes mellitus 2. typu u pacientov s autoimunitnou tyroiditídou v stádiu hypotyreózy.

INTRODUCTION: Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2T) are the two most common endocrinological diseases worldwide. The relationship between T1DM and autoimmune thyreopathies is known and described, but the relationship between thyreopathies and diabetes type 2 is not clarified sufficiently through that studies manifest increasingly the connection between them. OBJECTIVE: Investigate the prevalence of DM2T in patients with AIT in hypothyroid stadium and compare with common population and investigate a possible association between thyroid and glucose metabolism parameters. MATERIAL AND METHODS: The group consisted of 100 patients (33 men and 67 women) with AIT without until now documented glucose metabolism disorder, average age 65.63 ± 19.05 years. The control group (CG) consisted of 100 subjects without until now documented thyreopathy and glucose metabolism disorder (37 men and 63 women), average age 63.85 ± 18.98 years. We realised venous blood sampling and determined thyroidal and glycid metabolism parameters. RESULTS: The study did not confirm higher prevalence of diabetes in patients with AIT [3 (3 %) vs 4 (4 %), p = 1]. There were no statistical significant differences between glycid metabolism parameters in patients with AIT and CG. Also no glycid metabolism parameters correlated to thyroidal parameters. CONCLUSION: We did not confirm higher prevalence of DM in patients with AIT.Key words: autoimmune thyroiditis - diabetes mellitus type 2.

[Syndrome of inappropriate antidiuresis and the current management of hyponatremia]. / Syndróm neprimeranej antidiurézy (SIAD) a súcasný manazment hyponatriémie.

Hyponatremia defined as serum sodium lower than 135 mmol/L is the most common electrolyte abnormality in outpatients and also in hospitalized patients. It has been documented that hyponatremia is associated with significantly higher morbidity, mortality and longer hospitalization stay. Hyponatremia is manifested by variety of symptoms, from mild up to life threatening conditions. Syndrome of inappropriate antidiuresis (SIAD) is the most common type of hyponatremia. This article presents new aspects in the etiology, diagnosis, differential diagnosis ant treatment of the SIAD according to European guidelines.Key words: arginin-vasopressin-syndrome of inappropriate antidiuresis - diagnosis - hyponatremia - treatment.

[Diagnosis and management of metastatic pheochromocytoma and paraganglioma]. / Diagnostika a manazment metastatického feochromocytómu a paragangliómu.

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare catecholamine-producing neuroendocrine tumors arising from adrenal medulla or extra-adrenal sympathetic and parasympathetic ganglia. Most of the PHEOs/PGLs are benign tumors, but metastatic disease is common, especially in patients with particular genetic background. Although PHEOs/PGLs were described more than a century ago, diagnosis and therapy of metastatic disease are still challenging. Advances in understanding molecular and metabolic changes associated with tumorigenesis lead us to identification of the background of these tumors. Novel information allowed for development of more precise diagnostic methods and molecular therapeutic targets identification, which will improve care of patients with metastatic PHEO/PGL.Key words: diagnostics - management - paraganglioma - pheochromocytoma - therapy.

[Vitamin D and Polycystic Ovary Syndrome]. / Vitamín D a syndróm polycystických ovárií.

Currently there is growing evidence on possible influence of vitamin D (VD) on reproductive function in both females and males. The relationship between VD and clinical or laboratory manifestations of polycystic ovary syndrome (PCOS) seems to be mostly evaluated. Patients with PCOS have been demonstrated to have significantly lower levels of serum VD and they also have the higher prevalence of vitamin D deficiency as compared to controls. Some studies documented the relation of VD to serum androgen levels, other found that VD correlated with metabolic parameters (body weight, insulin resistance and lipid profile) only. Several interventional studies demonstrated that VD replacement improved these metabolic parameters in PCOS women with VD deficiency. On the other hand some studies also documented improvement of ovarian function and androgen levels. Also vitamin D replacement may represent an additional treatment in VD deficient PCOS women with the aim to improve phenotypic manifestations. It requires further randomized interventional studies on larger groups of patients.Key words: metabolic syndrome - polycystic ovary syndrome - vitamin D.

[Diagnostics of polycystic ovary syndrome]. / Diagnostika syndrómu polycystických ovárií.

UNLABELLED: Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. KEY WORDS: AES criteria - diagnosis - differential diagnosis - polycystic ovary syndrome.

[Diagnostics of polycystic ovary syndrome]. / Diagnostika syndrómu polycystických ovárií.

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist.

Increased adrenocortical activity in patients with vasovagal syncope.

OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH). DESIGN: Case-control study on patients with VVS and healthy controls. METHODS: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation. RESULTS: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 µg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate. CONCLUSION: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system.

Endoscopic Complications Are More Frequent in Levodopa-Carbidopa Intestinal Gel Treatment via JET-PEG in Parkinson's Disease Patients Compared to Nutritional PEG in Non-Parkinson's Disease Patients.

Background: To date, no studies comparing complication rates between patients with nutritional percutaneous endoscopic gastrostomy (N-PEG) and Parkinson's disease (PD) patients with percutaneous endoscopic gastro-jejunostomy (JET-PEG) for treatment administration have been published. Our study aimed to compare complication rates and the number of re-endoscopies between N-PEG and JET-PEG patients. Methods: Individuals requiring N-PEG or JET-PEG insertion between 2014 and 2021 were included in this single-center retrospective observational study. Complications were divided into time-related medical and technical complications. Reasons for post-insertion re-endoscopies and their number were also analyzed. Results: Eighty-seven subjects, 47 (54.02%) in JET-PEG group and 40 (45.98%) in the N-PEG group, were included. Early and technical complications were more frequent in JET-PEG vs. N-PEG subjects (70% vs. 10% [p < 0.001], and 54.5% vs. 5.1% [p < 0.001], respectively). The presence of psychiatric disease was associated with a higher number of early complications (p < 0.002). All three types of complications were significantly more frequent in subjects where a healthcare professional did not handle PEG (p < 0.001). Subjects with JET-PEG required a higher number of re-endoscopies compared to the N-PEG group (57.1% vs. 35%, p = 0.05). Conclusions: Complications are significantly more common in individuals with JET-PEG than those with N-PEG, which can be attributed to higher mobility in PD patients.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Thyroid hormones for euthyroid patients with simple goiter growing over time: a survey of European thyroid specialists.

BACKGROUND: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

Concomitant occurrence of Wernicke's encephalopathy and sarcopenia due to vitamin D depletion in patients with alcohol use disorder: a case report.

Individuals with alcohol use disorder frequently suffer from vitamin D deficiency, in addition to deficiencies in vitamins B12, folic acid and B1. This is due to inadequate dietary intake and behavioural changes. Each of these deficiencies results in different clinical symptoms. Subacute spinal cord degeneration, together with radicular and sensorimotor peripheral neuropathy, arises from B12 vitamin and folic acid deficiencies. B1 vitamin deficiency leads to Wernicke's encephalopathy, which can include the classical triad of symptoms (i.e. cognitive changes, ataxia and ophthalmoplegia). Sarcopenia is a consequence of a long-term deficiency of vitamin D. This current case report describes a 43-year-old female patient with alcohol use disorder who complained of dizziness, postural disturbance and episodes of intermittent paraesthesia. She was subsequently shown to have concomitant Wernicke's encephalopathy and sarcopenia due to vitamin D deficiency. This case report presents the diagnostic process undertaken to exclude conditions related to ataxia and paraparesis other than vitamins D and B1 deficiencies. It also emphasizes the importance of concomitant replacement of the depleted vitamins because the vitamin deficiency may occur simultaneously, which causes the accompanying manifestations of several clinical syndromes.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Bisphenol A as a Factor in the Mosaic of Autoimmunity.

The population worldwide is largely exposed to bisphenol A (BPA), a commonly used plasticizer, that has a similar molecular structure to endogenous estrogens. Therefore, it is able to influence physiological processes in the human body, taking part in pathophysiology of various endocrinopathies, as well as, cardiovascular, neurological and oncological diseases. BPA has been found to affect the immune system, leading to the development of autoimmunity and allergies, too. In the last few decades, the prevalence of autoimmune diseases has significantly increased that could be explained by a rising exposure of the population to environmental factors, such as BPA. BPA has been found to play a role in the pathogenesis of systemic autoimmune diseases and also organ-specific autoimmunity (thyroid autoimmunity, diabetes mellitus type 1, myocarditis, inflammatory bowel disease, multiple sclerosis, encephalomyelitis etc), but the results of some studies still remain controversial, so further research is needed.