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Best Practice & Research. Clinical... Mar 2023Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid... (Review)
Review
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.
Topics: Humans; Genetic Predisposition to Disease; Hashimoto Disease; Autoimmune Diseases; Graves Disease; Epigenesis, Genetic; Thyroid Diseases
PubMed: 35459628
DOI: 10.1016/j.beem.2022.101661 -
Best Practice & Research. Clinical... Mar 2023MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They are emerging as potential biomarkers and as therapeutic... (Review)
Review
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They are emerging as potential biomarkers and as therapeutic targets for several diseases including autoimmune thyroid diseases (AITD). They control a wide range of biological phenomena, including immune activation, apoptosis, differentiation and development, proliferation and metabolism. This function makes miRNAs attractive as disease biomarker candidates or even as therapeutic agents. Because of their stability and reproducibility circulating miRNAs have been an interesting area of research in many diseases, and studies describing their role in the immune response and in autoimmune diseases have progressively developed. The mechanisms underlying AITD remain elusive. AITD pathogenesis is characterized by a multifactorial interplay based on the synergy between susceptibility genes and environmental stimulation, together with epigenetic modulation. Understanding the regulatory role of miRNAs could lead to identify potential susceptibility pathways, diagnostic biomarkers and therapeutic targets for this disease. Herein we update our present knowledge on the role of microRNAs in AITD and discuss on their importance as possible diagnostic and prognostic biomarkers in the most prevalent AITDs: Hashimoto's thyroiditis (HT), Graves' disease (GD) and Graves' Ophthalmopathy (GO). This review provides an overview of the state of the art in the pathological roles of microRNAs as well as in possible novel miRNA-based therapeutic approaches in AITD.
Topics: Humans; MicroRNAs; Reproducibility of Results; Genetic Predisposition to Disease; Hashimoto Disease; Graves Disease; Autoimmune Diseases; Biomarkers; Graves Ophthalmopathy; Thyroid Diseases
PubMed: 36801129
DOI: 10.1016/j.beem.2023.101741 -
Thyroid : Official Journal of the... Mar 2024Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone... (Meta-Analysis)
Meta-Analysis
Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.
Topics: Humans; Autoantibodies; Dietary Supplements; Hashimoto Disease; Randomized Controlled Trials as Topic; Selenium; Thyrotropin
PubMed: 38243784
DOI: 10.1089/thy.2023.0556 -
Reviews in Endocrine & Metabolic... Apr 2023Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system... (Review)
Review
Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system and bone interact with each other, coined osteoimmunology. Hashimoto's thyroiditis (HT) is one of the most common chronic autoimmune diseases which is accompanied by lymphocytic infiltration. It shows elevating thyroid autoantibody levels at an early stage and progresses to thyroid dysfunction ultimately. Different effects exert on bone metabolism during different phases of HT. In this review, we summarized the mechanisms of the long-term effects of HT on bone and the relationship between thyroid autoimmunity and osteoimmunology. For patients with HT, the bone is affected not only by thyroid function and the value of TSH, but also by the setting of the autoimmune background. The autoimmune background implies a breakdown of the mechanisms that control self-reactive system, featuring abnormal immune activation and presence of autoantibodies. The etiology of thyroid autoimmunity and osteoimmunology is complex and involves a number of immune cells, cytokines and chemokines, which regulate the pathogenesis of HT and osteoporosis at the same time, and have potential to affect each other. In addition, vitamin D works as a potent immunomodulator to influence both thyroid immunity and osteoimmunology. We conclude that HT affects bone metabolism at least through endocrine and immune pathways.
Topics: Hashimoto Disease; Bone and Bones; Humans; Thyroid Gland; Thyroid Hormones; Osteoporosis; Vitamin D; Animals; Autoimmunity; Autoimmune Diseases
PubMed: 36509987
DOI: 10.1007/s11154-022-09778-x -
Endocrinologia, Diabetes Y Nutricion Jan 2022
Topics: Hashimoto Disease; Humans; Thyroiditis, Autoimmune
PubMed: 35232564
DOI: 10.1016/j.endien.2020.09.007 -
Nutrients May 2023Celiac disease (CD) and systemic lupus erythematosus (SLE) are two diseases intensively studied in all age groups, with an increasing incidence at the global level,... (Review)
Review
Celiac disease (CD) and systemic lupus erythematosus (SLE) are two diseases intensively studied in all age groups, with an increasing incidence at the global level, possibly due to the increased awareness of the diseases and their accurate diagnosis and as a consequence of the new research and innovation technologies that have appeared in medicine. The first is a controllable condition found in approximately 1% of the entire population in the form of a reaction to environmental stimuli affecting individuals with genetic susceptibility, causing gluten intolerance, gastrointestinal and extradigestive symptoms, starting from subclinical stages and culminating in severe malabsorption. On the other hand, lupus is an autoimmune disease with chameleon-like symptoms and found mainly in the female sex, which leaves its clinical mark on most organs, from the skin, eyes, and kidneys to the cardiovascular, pulmonary, neurological, osteoarticular, and hematological systems. Current studies focus on the correlation between celiac disease and other autoimmune pathologies such as autoimmune thyroiditis (Hashimoto and Graves-Basedow), type I diabetes, and systemic lupus erythematosus. The current review aims to present a summary of the data from the specialized literature regarding the intercurrents between celiac disease and lupus by analyzing the most recent studies published on PubMed.
Topics: Humans; Child; Female; Celiac Disease; Autoimmune Diseases; Lupus Erythematosus, Systemic; Thyroiditis, Autoimmune; Hashimoto Disease
PubMed: 37299501
DOI: 10.3390/nu15112535 -
Frontiers in Immunology 2022Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform.
METHODS
The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed.
RESULTS
A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found.
CONCLUSIONS
PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.
Topics: Humans; Hashimoto Disease; Mean Platelet Volume; Platelet Count; Graves Disease; Hyperthyroidism; Hypothyroidism
PubMed: 36618418
DOI: 10.3389/fimmu.2022.1089469 -
Trends in Immunology May 2023Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively.... (Review)
Review
Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.
Topics: Humans; Thyroiditis, Autoimmune; Hashimoto Disease; Graves Disease; Autoimmune Diseases
PubMed: 37061365
DOI: 10.1016/j.it.2023.03.007 -
The Surgical Clinics of North America Aug 2019The two most common autoimmune conditions of the thyroid include chronic lymphocytic (Hashimoto's) thyroiditis and Graves' disease. Both conditions can be treated... (Review)
Review
The two most common autoimmune conditions of the thyroid include chronic lymphocytic (Hashimoto's) thyroiditis and Graves' disease. Both conditions can be treated medically, but surgery plays an important role. Hashimoto's thyroiditis and Graves' disease are mediated by autoantibodies that interact directly with the thyroid, creating inflammation and impacting thyroid function. Patients may develop large goiters with compressive symptoms or malignancy requiring surgical intervention. In addition, there are several surgical indications specific to Hashimoto's and Graves' Disease.
Topics: Autoantibodies; Hashimoto Disease; Humans; Thyroid Gland; Thyroidectomy
PubMed: 31255196
DOI: 10.1016/j.suc.2019.04.005 -
Endokrynologia Polska 2021The phenomenon of autoimmunity develops as a result of the triggering factor released by damaged cells. This leads to an infiltration of CD4+ cells involved in... (Review)
Review
The phenomenon of autoimmunity develops as a result of the triggering factor released by damaged cells. This leads to an infiltration of CD4+ cells involved in stimulating the effector cells cytotoxicity and stimulating the humoral response. One of the most common autoimmune disorders are autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves's diseases. Helper T lymphocytes, which are divided into Th1, Th2, Tregs, and the relatively new groups Th17, Th22, and Th9, are involved in the pathogenesis of AITD. CD4+ cell subtypes mature and differentiate by specific transcription factors and in a specific interleukin environment. Not only are Th1 and Th2 cells involved in the development of AITD, but also Th17, Th22, and Th9 lymphocytes and their correlation to Tregs lymphocytes. The plasticity of the CD4+ cells is very important, affecting the balance between these cells, as well the factors modulating their phenotypic variability. Patients with AITD have an increased percentage of Th17, Th22, and Th9 cells as well as defective function of Tregs lymphocytes. The balance between Th17 cells (and also other cytotoxic T cells) and Treg cells is also very important. Understanding the role of CD4 cells in the pathogenesis of AITD may be important not only for the development of the knowledge, but also for determining therapeutic targets.
Topics: Autoimmune Diseases; CD4-Positive T-Lymphocytes; Graves Disease; Hashimoto Disease; Humans; T-Lymphocytes, Helper-Inducer
PubMed: 34647609
DOI: 10.5603/EP.a2021.0076