scholarly journals Role of iodine in pathogenesis of thyroid disease - is induction of apoptosis consequence of iodine cytotoxicity?

2017 ◽  
Vol 145 (5-6) ◽  
pp. 309-314
Author(s):  
Ljiljana Markovic
Keyword(s):  
Thyroid Disease ◽  
Transcriptional Control ◽  
Molecular Form ◽  
Hashimoto Thyroiditis ◽  
Epidemiological Studies ◽  
Thyroid Cell ◽  
Apoptotic Cells ◽  
Autoimmune Thyroid ◽  
Excess Iodine ◽  
High Concentrations

Iodine is one of the best-characterized environmental factors associated with autoimmune thyroid disease (ATD). Epidemiological studies have shown that ATD incidence has increased following the introduction of salt iodination in the 1920s; in addition, ATD patients can improve upon iodine restriction. In animal models such as BioBreeding/Worcester and Buffalo rats, obese chicken strain, and non-obese diabetic H-2h4 mice, excess iodine is associated with autoimmunity. Analyses of Hashimoto thyroiditis (HT) have shown enlarged number of apoptotic follicular cells, and the destruction is an effect of death receptormediated apoptosis. Excess of iodine induces rapid apoptosis of goitrogen Wistar pretreated rats, possibly connected with inhibition of polyamine synthesis, inhibitors of DNA fragmentation. Percentage of apoptotic cells was statistically higher in patients with HT than in those with euthyroid goiter, with significant increase of caspase 32. Genes for Bcl-2 and Bax proteins are under the transcriptional control of p53. In TAD-2 cell cultures, apoptosis is p53-independed, suggesting that DNA damage is not primarily evoked by potassium iodide (KI). High concentrations of NaI increase the proportion of apoptotic cells in FTRL5 thyroid cell line. Iodide cytotoxicity is inhibited by a TPO inhibitor and is relieved with an anti-oxidant agent. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue. Iodide excess requires peroxidase enzymatic activity to induce apoptosis. Ionic iodide is not directly toxic, whereas its molecular form I2 mediates the apoptotic effect of KI.

TSH RECEPTOR ANTIBODIES: RELEVANCE & UTILITY

2020 ◽  
Vol 26 (1) ◽  
pp. 97-106 ◽  
Author(s):  
George J. Kahaly ◽  
Tanja Diana ◽  
Paul D. Olivo
Keyword(s):  
Differential Diagnosis ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Hashimoto Thyroiditis ◽  
Rapid Diagnosis ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Blocking Antibody ◽  
Autoimmune Thyroid

Objective: Antibodies (Abs) to the thyrotropin (TSH) receptor (TSH-R) play an important role in the pathogenesis of autoimmune thyroid disease (AITD). We define the complex terminology that has arisen to describe TSH-R-Abs, review the mechanisms of action of the various types of TSH-R-Abs, and discuss significant advances that have been made in the development of clinically useful TSH-RAb assays. Methods: Literature review and discussion. Results: TSH-R-Abs may mimic or block the action of TSH or be functionally neutral. Stimulating TSH-R-Abs are specific biomarkers for Graves disease (GD) and responsible for many of its clinical manifestations. TSH-R-Abs may also be found in patients with Hashimoto thyroiditis in whom they may contribute to the hypothyroidism of the disease. Measurement of TSH-R-Abs in general, and functional Abs in particular, is recommended for the rapid diagnosis of GD, differential diagnosis and management of patients with AITD, especially during pregnancy, and in AITD patients with extrathyroidal manifestations such as orbitopathy. Measurement of TSH-R-Abs can be done with either immunoassays that detect specific binding of Abs to the TSH-R or cell-based bioassays that also provide information on their functional activity and potency. Application of molecular cloning techniques has led to significant advances in methodology that have enabled the development of clinically useful bioassays. When ordering TSH-R-Ab, clinicians should be aware of the different tests available and how to interpret results based on which assay is performed. The availability of an international standard and continued improvement in bioassays will help promote their routine performance by clinical laboratories and provide the most clinically useful TSH-R-Ab results. Conclusion: Measurement of TSH-R-Abs in general, and functional (especially stimulating) Abs in particular, is recommended for the rapid diagnosis, differential diagnosis, and management of patients with Graves hyperthyroidism, related thyroid eye disease, during pregnancy, as well as in Hashimoto thyroiditis patients with extra-thyroidal manifestations and/or thyroid-binding inhibiting immunoglobulin positivity. Abbreviations: Ab = antibody; AITD = autoimmune thyroid disease; ATD = antithyroid drug; cAMP = cyclic adenosine 3′,5′-monophosphate; ELISA = enzyme-linked immunosorbent assay; GD = Graves disease; GO = Graves orbitopathy; HT = Hashimoto thyroiditis; MAb = monoclonal antibody; TBAb = thyrotropin receptor blocking antibody; TBII = thyroid-binding inhibiting immunoglobulin; TSAb = thyrotropin receptor–stimulating antibody; TSB-Ab or TRBAb = thyrotropin receptor–stimulating blocking antibody; TSH = thyrotropin; TSH-R = thyrotropin receptor

scholarly journals CTLA-4 and its role in autoimmune thyroid disease

2003 ◽  
Vol 31 (1) ◽  
pp. 21-36 ◽  
Author(s):  
DA Chistiakov ◽  
RI Turakulov
Keyword(s):  
T Lymphocyte ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Cytotoxic T Lymphocyte ◽  
Thyroid Autoimmunity ◽  
Hashimoto Thyroiditis ◽  
Gene Encoding ◽  
Autoimmune Thyroid ◽  
Functional Studies

Autoimmune thyroid disease (AITD) occurs in two common forms: Graves' disease and Hashimoto thyroiditis. On the basis of functional and experimental data, it has been suggested that the gene encoding cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a candidate gene for conferring susceptibility to thyroid autoimmunity. In this review, we critically evaluate the evidence for pathogenetic involvement of CTLA-4 in the various forms of AITD and focus on the possible role of genetic variation of the CTLA4 locus. Population genetics data strongly suggest a role for the CTLA4 region in susceptibility to AITD. However, further functional studies are required to understand the significance of CTLA4 polymorphisms in the pathogenic mechanism of AITD.

scholarly journals Identification of Independent Susceptible and Protective HLA Alleles in Japanese Autoimmune Thyroid Disease and Their Epistasis

2014 ◽  
Vol 99 (2) ◽  
pp. E379-E383 ◽  
Author(s):  
Sho Ueda ◽  
Daisuke Oryoji ◽  
Ken Yamamoto ◽  
Jaeduk Yoshimura Noh ◽  
Ken Okamura ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Hla Antigens ◽  
Hashimoto Thyroiditis ◽  
Dual Function ◽  
Protective Effects ◽  
Hla Antigen ◽  
Hla Alleles ◽  
Autoimmune Thyroid ◽  
Susceptibility And Resistance

Background: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto thyroiditis (HT), which partially share immunological features. Determining the genetic basis that distinguishes GD and HT is a key to understanding the differences between these 2 related diseases. Aim: The aims of this study were to identify HLA antigens that can explain the immunopathological difference between GD and HT and to elucidate epistatic interactions between protective and susceptible HLA alleles, which can delineate the distinct function of HLA in AITD etiology. Design: We genotyped 991 patients with AITD (547 patients with GD and 444 patients with HT) and 481 control subjects at the HLA-A, HLA-C, HLA-B, DRB1, DQB1, and DPB1 loci. A direct comparison of HLA antigen frequencies between GD and HT was performed. We further analyzed an epistatic interaction between the susceptible and protective HLA alleles in the development of GD and HT. Results: We identified 4 and 2 susceptible HLA molecules primarily associated with GD and HT, respectively, HLA-B*35:01, HLA-B*46:01, HLA-DRB1*14:03, and HLA-DPB1*05:01 for GD and HLA-A*02:07 and HLA-DRB4 for HT. In a direct comparison between GD and HT, we identified GD-specific susceptible class II molecules, HLA-DP5 (HLA-DPB1*05:01; Pc = 1.0 × 10−9) and HLA-DR14 (HLA-DRB*14:03; Pc = .0018). In contrast, HLA components on 3 common haplotypes in Japanese showed significant protective effects against the development of GD and HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and HT). Interestingly, the representative protective HLA, HLA-DR13 (HLA-DRB1*13:02), was epistatic to susceptible HLA-DP5 in controlling the development of GD. Conclusion: We show that HLA exerts a dual function, susceptibility and resistance, in controlling the development of GD and HT. We also show that the protective HLA allele is partially epistatic to the susceptible HLA allele in GD.

scholarly journals Autoimmune Thyroid Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
M. A. Iddah ◽  
B. N. Macharia
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Cell Injury ◽  
Thyroid Diseases ◽  
Thyroid Cell ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Cell Responses ◽  
Genetic And Environmental Factors ◽  
The Relationship

Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice.

SERUM METABOLOMIC PATTERNS IN PATIENTS WITH AUTOIMMUNE THYROID DISEASE

2020 ◽  
Vol 26 (1) ◽  
pp. 82-96 ◽  
Author(s):  
Jia Liu ◽  
Jing Fu ◽  
Yumei Jia ◽  
Ning Yang ◽  
Jing Li ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Density Lipoprotein ◽  
Hashimoto Thyroiditis ◽  
Lipoprotein Cholesterol ◽  
Graves Disease ◽  
Model Assessment ◽  
Healthy Controls ◽  
Autoimmune Thyroid ◽  
Fasting Plasma

Objective: Autoimmune thyroid disease, including Graves disease (GD) and Hashimoto thyroiditis (HT), is one of the most common endocrine diseases. GD and HT are the main etiologies for hyperthyroidism and hypothyroidism, respectively. This study aimed to provide a metabolomic analysis of GD patients with hyperthyroidism and HT patients with hypothyroidism. Methods: This study investigated serum metabolomics in 43 GD patients with hyperthyroidism, 45 HT patients with hypothyroidism, and 52 age- and sex-matched healthy controls. The metabolomic data were analyzed by performing multivariate statistical analysis. Results: The 186 metabolites including amino acids, bile acids, free fatty acids, and lipids were identified in all participants. Multivariate models indicated systematic differences in the hyperthyroidism, hypothyroidism, and control groups. Compared to healthy controls, the 22 metabolites in the hyperthyroidism group and the 17 metabolites in the hypothyroidism group were significantly changed. Pathway analysis showed that hyperthyroidism had a significant impact on arginine and proline metabolism and aminoacyl-transfer ribonucleic acid biosynthesis, while hypothyroidism had a significant impact on alanine, aspartate, and glutamate metabolism. Conclusion: The serum metabolomic pattern changes in patients with autoimmune thyroid dysfunction. Abbreviations: BMI = body mass index; CA = cholic acid; CDCA = chenodeoxycholic acid; DCA = deoxycholic acid; FBG = fasting plasma glucose; FINS = fasting plasma insulin; FT3 = free triiodothyronine; FT4 = free thyroxine; GD = Graves disease; GDCA = glycodeoxycholic acid; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance; HT = Hashimoto thyroiditis; LDL-C = low-density lipoprotein cholesterol; PC = phosphatidylcholine; PCA = principal component analysis; PLS-DA = partial least squares discriminant analysis; SM = sphingomyelin; TBA = total bile acid; TC = total cholesterol; TG = triglyceride; TSH = thyrotropin; VIP = variable influences on projection

scholarly journals Autoimmune thyroid disease: propagation and progression

2003 ◽  
pp. 1-9 ◽  
Author(s):  
AP Weetman
Keyword(s):  
Immune System ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Large Scale ◽  
Thyroid Autoimmunity ◽  
Hla Class I ◽  
Iodine Intake ◽  
Thyroid Cell ◽  
Endogenous Factors ◽  
Autoimmune Thyroid

Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence.The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

EPIDEMIOLOGY OF AUTOIMMUNE THYROID DISEASE

2021 ◽  
pp. 8-12
Author(s):  
Brilla Balsam J ◽  
Lancelet T.S
Keyword(s):  
Environmental Factors ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Epidemiological Studies ◽  
Autoimmune Thyroid ◽  
Multifactorial Diseases ◽  
Complex Interactions ◽  
Causal Processes ◽  
Autoimmune Conditions ◽  
Genetic And Environmental Factors

Most diseases involve many genes in complex interactions, in addition to physical and cultural environmental factors. If a disease is caused by genetic and environmental factors, its etiological origin can be referred to as having a multifactorial pattern. The common multifactorial diseases encompass environmental inuences on the causal processes. Thyroid is a multifactorial type of origin of disease. The epidemiological studies show that if thyroid disease is caused by the interaction of both genetic and environmental factors, then mostly it is autoimmune thyroid disease. When the antibodies attack the thyroid gland, it is called Auto Immune Thyroid Disease (AITD). The present study attempts to examine whether the occurrence of thyroid disease in a micro area is due to autoimmune conditions. To prove the fact clinically, blood of thyroid patients were collected and tested in a laboratory. The result shows that most of the patients have autoimmune thyroid disease. Moreover, some environmental and genetic factors were also examined since thyroid disease is a multifactorial origin of disease.

Rheumatic Manifestations of Autoimmune Thyroid Disease: The Other Autoimmune Disease

2012 ◽  
Vol 39 (6) ◽  
pp. 1125-1129 ◽  
Author(s):  
CLEMENT E. TAGOE ◽  
ANNA ZEZON ◽  
SAAKSHI KHATTRI
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Fibromyalgia Syndrome ◽  
Connective Tissue Diseases ◽  
Lymphocytic Infiltration ◽  
Hashimoto Thyroiditis ◽  
Chronic Lymphocytic Thyroiditis ◽  
Autoimmune Thyroid ◽  
Normal Thyroid Function ◽  
Rheumatic Manifestations

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.

Sign in / Sign up

Export Citation Format

Share Document