Circulating levels of irisin and Meteorin-like protein in PCOS and its correlation with metabolic parameters.

INTRODUCTION: Research on obesity, which results from excessive food consumption and sedentary lifestyle, has focused on increasing energy expenditure. Recently, muscle tissue is being investigated as an endocrine active organ, secreting molecules called myokines. Multiple studies have been performed to assess myokine levels in various disorders, including polycystic ovary syndrome (PCOS) and metabolic syndrome. Irisin and Meteorin-like protein (Metrnl) are particles which, among others, are suggested to play an important role in adipose tissue browning and improving insulin sensitivity. MATERIAL AND METHODS: The study population consisted of 31 women with PCOS and 18 healthy individuals. PCOS was diagnosed based on revised 2003 Rotterdam criteria. Multiple anthropometrical, hormonal, and biochemical parameters were assessed, including oral glucose tolerance test and body composition with dual energy X-ray absorptiometry. Serum levels of irisin and Metrnl were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no differences between the PCOS and control groups according to age, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), or body mass composition. Assessment of Metrnl and irisin concentrations revealed no significant differences between PCOS and healthy women. The irisin level was negatively correlated with BMI, body fat mass, fasting glucose, and insulin concentrations. No relationship between Metrnl level and metabolic parameters was found. CONCLUSIONS: Although irisin seems to be a promising biomarker, inconsistent research limits its value in clinical use in the assessment or treatment of obesity. Metrnl level was not affected in the study population, but it might be connected to the severity of metabolic disturbances.

Alteration of Branched-Chain and Aromatic Amino Acid Profile as a Novel Approach in Studying Polycystic Ovary Syndrome Pathogenesis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive-age women and predisposes them to the development of metabolic disturbances. Recent research has shown that several metabolic factors may play a role in PCOS pathogenesis, and it has been suggested that an alteration in the amino acid profile might be a predictive sign of metabolic disorders. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are concepts that have attracted scientific attention; however, a universal definition has not been established yet for these terms. Already existing definitions of MHO involve the coexistence of obesity with the absence or minimal presence of other metabolic syndrome parameters. A group of 326 women, 209 diagnosed with PCOS and 117 healthy individuals, participated in this study. Multiple parameters were assessed, including anthropometrical, biochemical, and hormonal ones, and gas-liquid chromatography, combined with tandem mass spectrometry, was used to investigate the amino acid profile. Statistical analysis revealed noticeably higher levels of all aromatic amino acids in PCOS women compared to the control group: phenylalanine 47.37 ± 7.0 vs. 45.4 ± 6.09 nmol/mL (p = 0.01), tyrosine 61.69 ± 9.56 vs. 58.08 ± 8.89 nmol/mL (p < 0.01), and tryptophan 53.66 ± 11.42 vs. 49.81 ± 11.18 nmol/mL (p < 0.01); however, there was no significant difference in the "tryptophan ratio" between the PCOS and control group (p = 0.88). A comparison of MHO and MUO PCOS women revealed that LAP, leucine, and isoleucine concentrations were significantly higher among the MUO subgroup: respectively, 101.98 ± 34.74 vs. 55.80 ± 24.33 (p < 0.001); 153.26 ± 22.26 vs. 137.25 ± 25.76 nmol/mL (p = 0.04); and 92.92 ± 16.09 vs. 82.60 ± 18.70 nmol/mL (p = 0.02). No significant differences in BMI, fasting glucose, and HOMA-IR between MHO and MUO were found: respectively, 35.0 ± 4.8 vs. 36.1 ± 4.6 kg/m2 (p = 0.59); 88.0 ± 6.0 vs. 87.73 ± 6.28 mg/dL (p = 0.67); and 3.36 ± 1.70 vs. 4.17 ± 1.77 (p = 0.1). The identification of altered amino acid profiles in PCOS holds potential clinical implications. Amino acids may serve as biomarkers for diagnosing and monitoring the metabolic status of individuals with PCOS. The alteration of BCAAs and AAAs may be involved in PCOS pathogenesis, but the underlying mechanism should be further investigated.

Specific Alteration of Branched-Chain Amino Acid Profile in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive age women; it is a complex health issue with numerous comorbidities. Attention has recently been drawn to amino acids as they are molecules essential to maintain homeostasis. The aim of the study was to investigate the branch chain amino acid (BCAA) profile in women with PCOS. A total of 326 women, 208 diagnosed with PCOS and 118 healthy controls, participated in the study; all the patients were between 18 and 40 years old. Anthropometrical, biochemical and hormonal parameters were assessed. Gas-liquid chromatography combined with tandem mass spectrometry was used to investigate BCAA levels. Statistical analysis showed significantly higher plasma levels of BCAAs (540.59 ± 97.23 nmol/mL vs. 501.09 ± 85.33 nmol/mL; p < 0.001) in women with PCOS. Significant correlations (p < 0.05) were found between BCAA and BMI, HOMA-IR, waist circumference and total testosterone levels. In the analysis of individuals with abdominal obesity, there were significant differences between PCOS and controls in BCAA (558.13 ± 100.51 vs. 514.22 ± 79.76 nmol/mL) and the concentrations of all the analyzed amino acids were higher in the PCOS patients. Hyperandrogenemia in PCOS patients was associated with significantly higher leucine, isoleucine and total BCAA levels. The increase of BCAA levels among PCOS patients in comparison to healthy controls might be an early sign of metabolic alteration and a predictive factor for other disturbances.

Myokines in Acromegaly: An Altered Irisin Profile.

Introduction: The muscle is an endocrine organ controlling metabolic homeostasis. Irisin and myostatin are key myokines mediating this process. Acromegaly is a chronic disease with a wide spectrum of complications, including metabolic disturbances. Purpose: To examine the influence of acromegaly on irisin and myostatin secretion and their contribution to metabolic profile and body composition. Materials and Methods: In 43 patients with acromegaly and 60 controls, serum levels of irisin, myostatin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), parameters of glucose, and lipid metabolism were determined. Body composition was assessed with dual-energy x-ray absorptiometry. Results: The irisin concentration was significantly lower in patients with acromegaly compared to controls (3.91 vs. 5.09 µg/ml, p = 0.006). There were no correlations between irisin and GH/IGF-1 levels. In the study group, irisin was negatively correlated with fasting insulin (r = -0.367; p = 0.042), HOMA-IR (r = -0.510; p = 0.011), and atherogenic factors: Castelli I (r = -0.416; p = 0.005), Castelli II (r = -0.400; p = 0.001), and atherogenic coefficient (AC) (r = -0.417; p = 0.05). Irisin and myostatin concentrations were also lower in acromegalics with insulin resistance than without (2.80 vs. 4.18 µg/ml, p = 0.047; 81.46 vs. 429.58 ng/L, p = 0.018, respectively). There were no differences between study group and controls in myostatin concentration. Myostatin levels negatively correlated with GH (r = -0.306; p = 0.049), HOMA-IR (r = -0.046; p = 0.411), and insulin levels (r = -0.429; p = 0.016). Conclusions: Decreased irisin concentrations in acromegaly may suggest impaired hormonal muscle function contributing to metabolic complications in this disorder. However, learning more about the association between myostatin and GH in acromegaly requires further studies. Nevertheless, it appears that myostatin is not critical for muscle mass regulation in acromegaly.

Laboratory interference in the thyroid function test.

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are commonly used worldwide, and their results have an important influence on decisions about treatment and further diagnostic processes. Any discrepancies between symptoms and laboratory results or between results of different tests should be closely investigated to avoid misdiagnosis and unnecessary treatment. Inconsistencies in hormone tests might be a result of physiological changes in hormonal balance, a disease, drug intake, or laboratory interference. Major factors that interfere with thyroid function tests are: heterophilic antibodies, macro TSH, biotin, thyroid hormones autoantibodies, anti-streptavidin, and anti-ruthenium antibodies. In this paper we discuss the influence of different factors on the procedures of hormonal immunoassays, as well as methods to minimise the risk of false results and misdiagnoses.

An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts.

CONTEXT: The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients. OBJECTIVE: We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data. DESIGN AND PARTICIPANTS: rs3094228 was genotyped in 469 UK patients with GD using Taqman chemistry. Genotype frequencies were compared with genotypic data available from the Wellcome Trust case-control consortium using logistic regression analysis. To determine whether rs3094228 is independently associated with age of GD onset, the HLA DRB1*0301 tagging variant, rs535777, was also genotyped. RESULTS: The C allele of rs3094228 was overrepresented in the UK GD cohort compared with controls (P allele=5.08 × 10-9, odds ratio 1.76; [95% confidence interval, 1.46-2.13]). This association was more marked in young-onset GD (<30 years) (P allele=1.70 × 10-10 vs P allele=0.0008). The meta-analysis of UK and Polish data supported the association of the C allele with GD susceptibility (P allele=1.79 × 10-5) and age of onset (P allele=5.63 × 10-8). Haplotype analysis demonstrated that rs3094228 is associated with age of GD onset (P = 2.39 × 10-6) independent of linkage disequilibrium with HLA DRB1*0301. CONCLUSION: The rs3094228 HCP5 polymorphism is independently associated with GD susceptibility and age of onset in a UK GD cohort. Our findings indicate a potential role of long noncoding ribonucleic acids, including HCP5, in GD pathogenesis, particularly in the younger population.

Reduction of Posttraumatic Stress Disorder (PTSD) Symptoms in PTSD and Major Depressive Disorder Comorbidity After Acute Hypoglycemia-A Case Report.

Background: Approximately half of all patients with posttraumatic stress disorder (PTSD) also suffer from major depressive disorder (MDD). This co-occurrence might lead to an impairment of cognitive functions, worse response to antidepressant medications, and an increased risk of suicide in comparison to patients with PTSD alone. Prognosis for people with PTSD and MDD co-occurrence is poorer than for either one alone; therefore, researchers look for novel, effective treatments. Case Presentation: A patient with MDD with the co-occurrence of PTSD was admitted to the Department of Endocrinology with suspicion of adrenal insufficiency. In order to assess the adrenocorticotropin/cortisol axis, a standard insulin tolerance test was performed. After inducing a hypoglycemic episode with intravenous short-acting insulin, PTSD symptoms were reduced. To the best of our knowledge, this is the first report on the reduction of PTSD symptoms after performing an insulin tolerance test. Conclusion: Reduction of PTSD symptoms in PTSD and MDD comorbidity has been noticed after a hypoglycemic episode. This demonstrates the mutual dependencies between the endocrine and nervous systems, covered extensively by psychoneuroendocrinology.

Branched chain amino acids: Passive biomarkers or the key to the pathogenesis of cardiometabolic diseases?

The metabolomic approach to research on lifestyle diseases has led to the discovery of new potential biomarkers of pathological conditions as well as key metabolic pathways that may become targets of therapeutic intervention. Current evidence supports plasma branched chain amino acids (BCAAs) as potential diagnostic and prognostic biomarkers of cardiometabolic diseases. However, the biological mechanisms of the associations that have been identified are still not completely understood and should be clarified before implementing BCAA-based biomarkers in the clinical setting. The most crucial issue that needs to be solved first is determining whether BCAA plasma profile disturbances are only passive biomarkers or whether they facilitate dysmetabolic processes. In this context, further research is also warranted to investigate the role of dietary BCAAs. Gaining this knowledge would be significant progress in molecular nutrition research, providing perspective for target therapeutic and prophylactic interventions. This paper provides a comprehensive review of the main hypotheses and mechanistic models that consider circulating BCAAs both as passive biomarkers and as contributors to cardiometabolic diseases.

Effects of running a marathon on irisin concentration in men aged over 50.

Our aim was to verify whether running a marathon is associated with changes in irisin concentration in healthy, endurance-trained men. In an observational study, we assessed baseline biochemical and fitness parameters of 28 middle-aged runners (mean ± SD age, BMI, VO2max: 58 ± 8 years; 24.5 ± 3 kg/m2; 51.1 ± 1.7 ml/kg/min). We evaluated irisin before, immediately after, and 7 days after the marathon. Irisin concentration decreased from a baseline value of 639 ± 427 to 461 ± 255 ng/ml immediately after the marathon (p < 0.05). After 7 days, it was still significantly lower than before the race, at 432 ± 146 ng/ml (p < 0.05). We found no correlations between irisin concentration and the training history of the studied subjects. We conclude that a long-distance run may have a negative impact on irisin release in men. This effect was not correlated with the training history of runners.

Paediatric-onset and adult-onset Graves' disease share multiple genetic risk factors.

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disease (AITD) with a peak incidence between 30 and 50 years of age. Although children and adolescents may also develop the disease, the genetic background of paediatric-onset GD (POGD) remains largely unknown. Here, we looked for similarities and differences in the genetic risk factors for POGD and adult-onset GD (AOGD) as well as for variants associated with age of GD onset. MATERIALS AND METHODS: A total of 1267 GD patients and 1054 healthy controls were included in the study. Allele frequencies of 40 established and suggested GD/AITD genetic risk variants (39 SNPs and HLA-DRB1*03) were compared between POGD (N = 179), AOGD (N = 1088) and healthy controls. Subsequently, multiple linear regression was used to explore the relationship between age of GD onset and genotype for each locus. RESULTS: We identified six POGD risk loci, all of them were also strongly associated with AOGD. Although for some of the analysed variants, including HCP5 (rs3094228), PRICKLE1 (rs4768412) and SCGB3A2 (rs1368408), allele frequencies differed nominally between POGD and AOGD patients, these differences were not significant after applying multiple testing correction (Pcor  = 0.05/40 = 1.25 × 10-3 ). Regression analysis showed that patients with higher number of HCP5 risk alleles tend to have a significantly earlier onset of GD (P = 6.9 × 10-5 ). CONCLUSIONS: The results of our study revealed that POGD and AOGD share multiple common genetic risk variants. Moreover, we demonstrated for the first time that HCP5 polymorphism is associated with an earlier age of GD onset in a dose-dependent manner.

Anaplastic thyroid carcinoma with rapid thyrotoxicosis - a case report and the literature review.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies and constitutes approximately 1.6-5% of the malignant neoplasms of the thyroid gland. ATC usually manifests itself with the local symptoms due to a rapidly enlarging thyroid mass, and as other thyroid cancers, has only seldom been reported to cause thyrotoxicosis. Up to now only 9 cases of ATC with concomitant thyrotoxicosis have been described. CASE REPORT: We report a rare case of a 66-year-old woman, who had had the preexisting large, euthyroid multinodular goiter for almost 50 years. She was consulted by a doctor because of a 4-week history of thyrotoxicosis, symptoms of the congestive heart failure and a rapid increase in the size of the goiter. Thyroid hormone levels were consistent with a hyperthyroid state. The fine-needle aspiration biopsy confirmed a diagnosis of the anaplastic thyroid carcinoma, the small cells variant. The 99m Tc-pertechnetate scintigraphy visualized non-homogenous tracer distribution with hot nodules. She was given a doxorubicin (20 mg/week) and required the continuous antithyroid treatment. The patient died a one year after the first symptoms of the disease occurred. DISCUSSION: The association between ATC and a thyrotoxic state is very rare. In most cases, thyrotoxicosis concomitant with ATC was thought to be a result of the destruction of the thyroid follicles by the rapid infiltration with malignant cells, resulting in the leakage of preformed hormones to the circulation. In that case the most probable cause of thyrotoxicosis was the multinodular goiter coexisting with ATC. A simultaneous onset of tumor growth, thyrotoxicosis and a relatively long survival time of our patient is worth to notice and discuss.

Specific plasma amino acid disturbances associated with metabolic syndrome.

PURPOSE: The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. METHODS: Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(-): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed. The ability of the BCAA and AAA to discriminate subjects with MS and insulin resistance was tested. Based on logistic discrimination, a multivariate early MS diagnostic model was built, and its discrimination properties were evaluated. RESULTS: Two functionally independent amino acid clusters were identified. BCAA and phenylalanine differed significantly between MS(+) and MS(-) participants (P = 0.003). These factors were also found to be indicators of MS(+) individuals (AUC: 0.66; 95% CI: 0.5757-0.7469), and correlated with cardiometabolic factors. No statistically significant differences in amino acid concentrations between those with and without insulin resistance were noted, and none of the amino groups were indicators of insulin resistance. The proposed MS multivariate diagnostic model consisted of phenylalanine, insulin, leptin, and adiponectin, and had good discrimination properties [AUC 0.79; 95% CI: 0.7239-0.8646]. CONCLUSIONS: MS is associated with selective BCAA and AAA profile disturbances, which could be part of cardiometabolic disease pathogenesis and derive neither directly from insulin sensitivity impairment, nor obesity or muscle mass. The MS diagnostic model developed and described herein should be validated in future studies.

Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions.

BACKGROUND: Metallothioneins (MTs) are involved in numerous cell processes such as binding and transport of zinc and copper ions, differentiation, proliferation and apoptosis, therefore contributing to carcinogenesis. Scarce data exist on their expression in benign and malignant lesions of the thyroid. MATERIALS AND METHODS: mRNA expression of functional isoforms of MT genes (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT4) was studied in 17 nodular goiters (NG), 12 follicular adenomas (FA) and 26 papillary thyroid carcinomas (PTC). RESULTS: One-way ANOVA revealed significant differences in mRNA expression levels of MT1A (p<0.05), MT1E (p<0.005), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.005) in the analyzed samples. Post hoc analysis confirmed a significantly lower expression of MT1A mRNA in PTC compared to NG (p<0.05). Significant down-regulation was also noted for other MT isoforms in PTC in comparison to NG: MT1E (p<0.05), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.05). In addition, significant down-regulation of MT1F and MT1G in FA compared to NG was observed (p<0.005 and p<0.05, respectively). CONCLUSION: Expression of functional MT isoforms may contribute to thyroid carcinogenesis and potentially serve as a diagnostic marker in distinguishing benign and malignant lesions.

Gender-dependent and age-of-onset-specific association of the rs11675434 single-nucleotide polymorphism near TPO with susceptibility to Graves' ophthalmopathy.

The role of TPO gene polymorphism in the susceptibility to Graves' disease (GD) remains unclear. However, single-nucleotide polymorphisms (SNPs) near TPO have been recently associated with serum levels of thyroid peroxidase (TPO) antibody in two independent genome-wide association studies. Moreover, we have observed a strong association between the rs11675434 SNP located near TPO and the presence of clinically evident Graves' ophthalmopathy (GO). The aim of the current study was to reevaluate and dissect this association in an extended group of 1231 well-characterized patients with GD (1043 adults and 188 children) and 1130 healthy controls from the Polish Caucasian population, considering possible gender-dependent and age-of-onset-specific effects of the studied SNP. We found that the T allele of rs11675434 was significantly more frequent in GD patients with than without GO (odds ratio (OR)=1.26, 95% confidence interval (CI)=1.05-1.51, P=0.012), which was consistent with our previous findings. Further analyses performed in subgroups of patients showed that the association with GO was significant in adult patients with age of GD onset ⩾45 years (OR=1.34, 95% CI=1.03-1.75, P=0.031), but not in children and adolescents or adult patients with earlier onset of the disease (OR=1.72, 95% CI=0.77-3.84, P=0.18 and OR=1.05, 95% CI=0.79-1.40, P=0.75, respectively). Moreover, a strong association with GO was present in males (OR=2.06, 95% CI=1.40-3.02, P=0.0002), whereas it was absent in females (OR=1.10, 95% CI=0.90-1.35, P=0.35). The results of our study further suggest that rs11675434 SNP located near TPO is associated with the development of GO, especially in males and patients with later age of GD onset.

CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves' disease and modulates clinical phenotype of disease.

Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR-RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)-PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT16-21)/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT<16)GT(m) haplotypes increased risk of Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT16-21)GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT>21)GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT<16)GG(m) haplotype was predominantly observed in patients without Graves' orbitopathy, whereas TCA(AT16-21)GG(m) was absent in those patients. TCA(AT16-21)GG(m) occurred in patients with a mild Graves' orbitopathy outcome. The marker CTLA-4g.*642AT(8_33) was the only independent Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT>21]/[AT>21] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a pathogenetic role.

Regulatory lymphocytes in thyroid orbitopathy and autoimmune thyroid diseases.

Thyroid orbitopathy (OT), as an organ­specific autoimmune disease, is a result of immune dysregulation leading to loss of control over inflammation directed against self­antigens. The source of the autoreactive lymphocytes is the impairment of central tolerance as well as their induction on the periphery by modified or sequestered by that time antigens. Active suppression by the various subpopulations of regulatory lymphocytes (Lreg) acts as a counterbalance to the proinflammatory factors and is aimed at dampening pathological reaction. Thereby, qualitative or quantitative shortfalls of Lreg play a critical role in the development of autoimmune diseases. Giving direction to Lreg­based therapy and restoring the dynamic balance seem to be of crucial importance, especially in diseases such as OT, where the causative self­antigen is not yet unequivocally elucidated. Technical difficulties with isolation and assessment of Lreg function in vitro as well as lack of unification of research protocols make the findings non­comparable, inconclusive and sometimes even conflicting. Lack of a Tregs' (regulatory T cells) specific set of surface markers makes the demethylation status analysis of TSDR (Treg specific demethylated region) FOXP3 (forkhead box P3) locus the most reliable method of their quantification. Despite numerous discrepancies between research findings, most of them point to Lreg's pivotal role in immune disturbances, which form the basis of OT and autoimmune thyroid diseases (AITD).

GO-QOL--disease-specific quality of life questionnaire in Graves' orbitopathy.

The main goal of therapy for Graves' orbitopathy (GO) is to restore visual function and to improve quality of life (QOL); therefore, the idea of self-assessment of eye changes by the patient has been developed. We developed a validated Polish version of the GO-QOL questionnaire (GO-QOLpl). As an original version we used the English version of GO-QOL, which consists of 15 questions summarised in two subscales. GO-QOLpl was translated and validated in accordance with standard principles for translation of patient-reported outcomes (PRO). GO-QOLpl is a linguistically validated version of the original GO-QOL questionnaire, which is recommended by the European Group of Graves' Orbitopathy (EUGOGO). We strongly support the use of GO-QOLpl for the assessment of QOL among Polish patients with GO in clinical practice.

Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution.

Irisin (Ir), a recently identified adipo-myokine, cleaved and secreted from the protein FNDC5 in response to physical activity, has been postulated to induce the differentiation of a subset of white adipocytes into brown fat and to mediate the beneficial effects on metabolic homeostasis. Metabolic syndrome (MS), a cluster of factors leading to impaired energy homeostasis, affects a significant proportion of subjects suffering from polycystic ovary syndrome (PCOS). The aim of our study was to investigate the relationship between Ir plasma concentrations and metabolic disturbances. The study group consisted of 179 PCOS patients and a population of 122 healthy controls (both groups aged 25-35 years). A subset of 90 subjects with MS was isolated. A positive association between Ir plasma level and MS in the whole group and in controls was found. In subjects with high adipose body content (>40%), Ir was higher than in lean persons (<30%). Our results showed a significant positive association between Ir concentration and android type of adipose tissue in the whole study group and in the control group. Understanding the role of Ir in increased energy expenditure may lead to the development of new therapeutics for obesity and obesity-related diseases.

[Irisin--a new mediator of energy homeostasis]. / Iryzyna ­ nowy mediator homeostazy energetycznej

Skeletal muscles as an active hormonal compartment in the response of physical activity secrete substances named myokines capable of modulating metabolic processes. Myokines take part in communication between muscles and other tissues. Irisin (Ir) - a newly discovered adipomyokine - is cleaved and secreted to the circulation from a fibronectin type III domain containing protein 5 (FNDC5). The mechanism of Ir action has not been described precisely, and receptors for the molecule are not defined yet, but it has been proposed to promote browning of white adipose tissue into beige fat cells. To date we have distinguished two types of adipose tissue in mammals - white, which not only functions as a store of energy but also can play a pro-inflammatory role (secreting adipokines), and brown adipose tissue. Brown adipose tissue has a high mitochondrial content and can dissipate chemical energy in the form of heat (nonshivering termogenesis). It plays a natural antiobesity role and protects against obesity-related diseases. The development of beige adipose tissue, which in its structure and function is similar to brown adipose tissue, and the possibility to modify its amount through some external factors, are nowadays among the most important targets of research on fat cell biology.