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Serum metabolomic analysis in patients with Hashimoto's thyroiditis. Frontiers in endocrinology Background:Hashimoto's thyroiditis, an autoimmune thyroid disease, shows high morbidity worldwide, particularly in female. Patients with Hashimoto's thyroiditis have an increasing risk of hypothyroidism during the occurrence and progression of Hashimoto's thyroiditis. In recent years, metabolomics has been widely applied in autoimmune diseases, especially thyroid disorders. However, metabolites analysis in Hashimoto's thyroiditis is still absent. Methods:A total of 92 samples were collected, including 35 cases in the control group, 30 cases in the Hashimoto's thyroiditis with euthyroidism group, and 27 cases in the Hashimoto's thyroiditis with subclinical hypothyroidism group. SPSS 25.0 for statistical analysis and ROC curve, SIMCA 14.0, Metaboanalysis for multifactor analysis, and Origin 2021 for correlation analysis. Results:21 metabolites were identified. 10 metabolites were obtained from control group versus HTE group, 8 serum metabolites were abnormal between control group and HTS group, 3 metabolites were derived from HTE group versus HTS. Kyoto Encyclopedia of Genes and Genomes Enrichment analysis showed that fatty acid degradation, Arginine, and proline metabolism have a significant impact on HTE, while lysine degradation, tyrosine metabolism play an important role HTS group, compared to control group. In the comparison between the HTE and HTS group, Valine, leucine, and isoleucine degradation and Valine, leucine, and isoleucine biosynthesis exists a key role. Correlation analysis shows clinical are not related to metabolites. ROC curve indicates SM, LPC, PC can efficiency in identification patients with HT in different clinical stage from healthy individuals. Conclusion:Serum metabolites were changed in HT. Phospholipids such as SM, LPC, PC influence the pathogenesis of Hashimoto's thyroiditis. Fatty acid degradation and lysine degradation pathways have an impact on different clinical stage of HT. 10.3389/fendo.2022.1046159
Integrative Analyses of Genes Associated with Hashimoto's Thyroiditis. Journal of immunology research OBJECTIVE:Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is a common autoimmune thyroiditis, which mostly occurs in young and middle-aged women. It can be manifested as hyperthyroidism in the early stage; hypothyroidism may appear with the progression of the disease. Studies have shown that multiple factors such as heredity, environment, and autoimmunity are involved in the pathogenesis, but the specific mechanism is not clear. In our study, we tried to find key genes and potential molecular mechanisms of Hashimoto's thyroiditis to provide new ideas for the therapeutic targets of Hashimoto's thyroiditis. METHOD:GSE138198 and GSE54958 were downloaded from the GEO database, and two datasets were combined for analysis. The combined data were normalized to identify the differentially expressed genes (DEGs), and GO and KEGG enrichment analyses were performed. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. We also used the miRWalk database to identify regulatory miRNAs associated with expressions of DEGs. RESULT:We identified 182 DEGs (160 upregulated and 22 downregulated) between Hashimoto's disease patients and the healthy control group. GO analysis showed that DEGs were mostly concentrated in detection of chemical stimulus involved in sensory perception, intermediate filament cytoskeleton, and olfactory receptor activity. KEGG pathway analysis showed that DEGs were mainly related to olfactory transduction. Some members of the KRTAP family and HTR5A, KNG1, DRD3, HTR1D, TAS2R16, INSL5, TAS2R42, and GRM7 are the most important hub genes in the PPI network. In addition, we recognized that OTUD4, LLPH, and ECHDC1 were the most important hub genes in the miRNA-target gene network. CONCLUSION:In this study, a series of bioinformatics analyses of DEGs were performed to identify the key genes and pathways associated with Hashimoto's thyroiditis. These genes and pathways provide a more detailed understanding of the pathogenesis of Hashimoto's disease and provide new ideas for the therapeutic targets of Hashimoto's thyroiditis. 10.1155/2021/8263829
Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events. Frontiers in cell and developmental biology BACKGROUND:Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. METHODS:This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing. FINDINGS:We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 . The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment. INTERPRETATION:These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT. 10.3389/fcell.2021.685522
Fetal cell microchimerism: a protective role in autoimmune thyroid diseases. Cirello Valentina,Rizzo Roberta,Crippa Milena,Campi Irene,Bortolotti Daria,Bolzani Silvia,Colombo Carla,Vannucchi Guia,Maffini Maria Antonia,de Liso Federica,Ferrero Stefano,Finelli Palma,Fugazzola Laura European journal of endocrinology OBJECTIVE:The physiological persistence of fetal cells in the circulation and tissue of a previously pregnant woman is called fetal cell microchimerism (FCM). It has been hypothesized to play a role in systemic autoimmune disease; however, only limited data are available regarding its role in autoimmune thyroid disease (AITD). DESIGN:Circulating FCM was analyzed in a large series of previously pregnant women with Graves' disease (GD), Hashimoto's thyroiditis (HT), or no disease (healthy controls (HCs)). To exclude the possible bias related to placental factors, the polymorphic pattern of human leukocyte antigen-G (HLA-G) gene, which is known to be involved in the tolerance of fetal cells by the maternal immune system, was investigated. METHODS:FCM was evaluated by PCR in the peripheral blood, and the Y chromosome was identified by fluorescence in situ hybridization in some GD tissues. HLA-G polymorphism typing was assessed by real-time PCR. RESULTS:FCM was significantly more frequent in HC (63.6%) than in GD (33.3%) or HT (27.8%) women (P=0.0004 and P=0.001 respectively). A quantitative analysis confirmed that circulating male DNA was more abundant in HC than it was in GD or HT. Microchimeric cells were documented in vessels and in thyroid follicles. In neither GD/HT patients nor HC women was the HLA-G typing different between FCM-positive and FCM-negative cases. CONCLUSION:The higher prevalence of FCM in HC as compared to GD and HT patients suggests that it plays a possible protective role in autoimmune thyroid disorders. Placental factors have been excluded as determinants of the differences found. The vascular and tissue localization of microchimeric cells further highlights the ability of those cells to migrate to damaged tissues. 10.1530/EJE-15-0028
Serum levels of advanced glycation end products (AGEs) are increased and their soluble receptor (sRAGE) reduced in Hashimoto's thyroiditis. Ruggeri R M,Barbalace M C,Cristani M T,Alibrandi A,Giovinazzo S,Giuffrida G,Trimarchi F,Cannavò S,Campennì A Journal of endocrinological investigation PURPOSE:Advanced glycation end products (AGEs) are increased in conditions of oxidative stress and promote inflammation by interacting with their receptor RAGE on cell membrane. By contrast, the soluble receptor sRAGE exerts protective effects by competing with RAGE for ligand binding. AGEs/sRAGEs interaction is involved in the pathogenesis of several diseases related to oxidative stress. In the present study, we evaluated the AGEs/sRAGEs oxidative balance in Hashimoto' thyroiditis (HT). METHODS:We measured the levels of sRAGE, by ELISA, and AGEs, by spectrophotometric method, in the serum of 50 HT patients (5 M, 45 F; mean age 38.5 ± 12 years) and 50 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy. RESULTS:Serum sRAGEs were significantly lower (median 424 vs 738 pg/ml; p = 0.001) and AGEs higher (205 vs 114 AU/g prot; p = 0.001) in HT patients compared to controls, and the two parameters were inversely correlated (p = 0.016). Accordingly, the AGEs/sRAGEs ratio was threefold higher in HT patients than controls (0.48 vs 0.15; p = 0.0001). In regression analysis models, serum TPO-Ab were the main predictors for AGEs and sRAGEs levels and AGEs/sRAGEs ratio (p < 0.0001), irrespective of TSH and/or FT4 values. CONCLUSION:sRAGEs were decreased and AGEs increased, suggesting a dysregulation of AGE/sRAGEs-related oxidative homeostasis in HT patients, even when in euthyroid status. Autoimmunity per se seems to play an important role in AGEs/sRAGE imbalance, irrespective of thyroid function alterations. 10.1007/s40618-020-01231-7
Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis. Ruggeri Rosaria M,Vicchio Teresa M,Cristani Mariateresa,Certo Rosaria,Caccamo Daniela,Alibrandi Angela,Giovinazzo Salvatore,Saija Antonina,Campennì Alfredo,Trimarchi Francesco,Gangemi Sebastiano Thyroid : official journal of the American Thyroid Association BACKGROUND:Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins--were evaluated as potential new markers of oxidative stress in this disease. METHODS:This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. RESULTS:Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). CONCLUSIONS:Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT. 10.1089/thy.2015.0592
Evaluation of paraoxonase activity and association with serum advanced glycation end products as reliable markers of oxidative stress in Hashimoto's thyroiditis. Minerva endocrinology BACKGROUND:Oxidative stress has been implicated in the pathogenesis of autoimmune thyroiditis, also referred to as Hashimoto's thyroiditis (HT), and several biomarkers have been measured to evaluate the impact and clinical relevance of oxidative stress in this setting. Recently, advanced glycation end products (AGEs) have been proposed as reliable markers of oxidative stress in HT. In the present study, we investigated the relationship of AGEs with antioxidant paraoxonase (PON-1) activity as potential combined markers of oxidative stress. MATERIALS AND METHODS:We measured the levels of AGEs, and advanced oxidation protein products (AOPPs) and PON-1 activity by spectrophotometric methods, in the serum of 40 HT patients (36 F; mean age 35.4 ± 11.5 yr) and 38 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy. RESULTS:Serum levels of AGEs were significantly higher (median 378 vs 290 AU/g protein; P<0.001), while PON1 activity was significantly lower (median 165 vs 201 U/L; P<0.05) in HT patients compared to controls: the two parameters were inversely correlated (P<0.01), clearly indicating a pro-oxidant imbalance in HT patients. At stepwise regression analysis, TPOAb positivity was an independent predictor of both PON-1 activity (P = 0.002) and AGEs levels (P = 0.000). CONCLUSIONS:Increased formation and accumulation of AGEs contribute to enhanced oxidative stress, along with a decrease in PON-1 activity in HT. As a consequence, AGEs levels and alteration in PON 1 may serve as useful markers for monitoring the levels of oxidative stress in this disorder. 10.23736/S2724-6507.22.03931-8
The effect of spironolactone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis. Krysiak Robert,Kowalcze Karolina,Okopień Bogusław Journal of clinical pharmacy and therapeutics WHAT IS KNOWN AND OBJECTIVE:Hashimoto's thyroiditis, also referred to as autoimmune thyroiditis, is characterized by sexual dimorphism, suggesting an important role of sex hormones in its development. No interventional study has investigated whether drugs exerting antiandrogen properties affect thyroid antibody titres and thyroid function tests in subjects with autoimmune thyroiditis. METHODS:This study included 35 levothyroxine-naïve men with euthyroid Hashimoto's thyroiditis. At the physician's discretion, 18 men were then treated with spironolactone (50-200 mg daily), while the remaining patients (n = 17) received other diuretics. Serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as titres of thyroid peroxidase and thyroglobulin, were measured at the beginning of the study and 6 months later. Based on hormone levels, constant structure parameters of thyroid homeostasis were calculated. RESULTS AND DISCUSSION:At baseline, there was no difference between the treatment arms in terms of thyroid antibody titres, hormone levels and the calculated parameters of thyroid homeostasis. Thirty-two patients completed the study. Spironolactone increased thyroid antibody titres, decreased testosterone and 25-hydroxyvitamin D levels and reduced SPINA-GT. The drug produced a neutral effect on serum levels of thyrotropin, free thyroid hormones, Jostel's thyrotropin index and SPINA-GD. The effect of spironolactone on antibody titres correlated with treatment-induced changes in SPINA-GT, testosterone and 25-hydroxyvitamin D. No significant changes in antibody titres, hormone levels and the calculated parameters of thyroid homeostasis were observed in spironolactone-naïve men. WHAT IS NEW AND CONCLUSION:The obtained results indicate that spironolactone may exert an unfavourable effect on progression of autoimmune thyroiditis in men. 10.1111/jcpt.13046
Deciphering the Metabolomics-Based Intervention of Yanghe Decoction on Hashimoto's Thyroiditis. Evidence-based complementary and alternative medicine : eCAM Background:Yanghe decoction is a famous formula consisting of , deer horn gum, cinnamon, rue, , ginger charcoal, and licorice. However, few studies have explored the role of the potential mechanism of Yanghe decoction in the treatment of Hashimoto's thyroiditis by metabolomics. Methods:Nine mice were randomly divided into three groups: control group (group C), model group (group M), and drug administration group (group T), with three mice in each group. Mice in groups M and T were established as models of Hashimoto's thyroiditis, and group T was treated with Yanghe decoction. The metabolome of plasma samples from each group of mice was determined using mass spectrometry coupled with high-performance liquid and gas phases, and nuclear magnetic resonance. Based on the three assays, principal component analysis was performed on all samples, as well as orthogonal partial least squares-discriminant analysis and differential metabolite molecules for groups M and T. Subsequently, pathway enrichment analysis was performed, and the intersection was taken for the differential metabolites screened in the M and T groups. The levels of inflammatory factors IL-35 and IL-6 within the serum of each group of mice were detected. Results:The difference analysis showed that a total of 38 differential metabolites were screened based on mass spectrometry coupled with the high-performance liquid phase, 120 differential metabolites were screened based on mass spectrometry coupled with gas phase, and a total of -glucose and -glucose were the differential metabolites analyzed based on NMR test results. The pathways enriched by the differential metabolites in the M and T groups were intersected, and a total of 5 common pathways were obtained (amino acid tRNA biosynthesis, D-glutamine and D-glutamate metabolism, tryptophan metabolism, nitrogen metabolism, and arginine and proline metabolism). The results also showed a significant decrease in the serum inflammatory factor IL-35 and a significant increase in IL-6 in mice from group M compared with group C, while a significant increase in the serum inflammatory factor IL-35 and a significant decrease in IL-6 in mice from group T compared with group M. Conclusion:Our study reveals the metabolites as well as a metabolic network that can be altered by Yanghe decoction treatment of Hashimoto's thyroiditis and shows that Yanghe decoction can effectively reduce the level of inflammatory factors in Hashimoto's thyroid. 10.1155/2022/6215573
Medication Counseling for Thyroxine. Kalra Sanjay,Unnikrishnan A G,Tiwaskar Mangesh,Sahay Rakesh,Saboo Banshi,Negalur Vijay,Khandelwal Deepak,Gupta Pritam,Ghosh Sujoy,Das A K,Bantwal Ganapathi,Bajaj Sarita,Agarwal Sameer,Aggarwal Rashmi,Agarwal Navneet Indian journal of endocrinology and metabolism This communication from the National Indian Patient-centered Thyroid Management group provides a useful tool to help in medication counseling during hypothyroidism management. The authors classify and list aspects of thyroxine use which must be discussed with patients on thyroxine supplementation or replacement. Issues related to concomitant food and medications intake, preconception and pregnancy management, as well as sick day care, are also discussed. 10.4103/ijem.IJEM_91_17
Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule on experimental autoimmune thyroiditis in female rats. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan OBJECTIVE:To observe the effects of Buzhong Yiqi granule on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis (EAT). METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine. Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, selenium yeast (PC) group, low dose Buzhong Yiqi (BZYQ-L) group, medium dose Buzhong Yiqi (BZYQ-M) group and high dose Buzhong Yiqi (BZYQ-H) group. After two months of drug intervention according to dosage, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) in peripheral blood of rats. The pathological changes of rat thyroid tissues were observed under light microscope with HE staining; ELISA was used to determine estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-müllerian hormone (AMH), and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining. RESULTS:Compared with the NC group, BZYQ granule improved the thyroid and ovarian tissue morphology, and the levels of TPOAb, TGAb and TSH in the model group rats significantly increased ( 0.05), the thyroid tissue was severely destroyed, the levels of E2, FSH, LH, T, AMH significantly increased ( 0.05), and the ovary exhibited polycystic changes; Compared with the model group, TSH level in the BZYQ-L group rats decreased ( 0.05), FSH, T, AMH levels decreased ( 0.05), in the BZYQ-M group TPOAb, TSH levels decreased ( 0.05), FSH, LH, T, AMH levels significantly decreased ( 0.05), BZYQ-H group TPOAb, TGAb, TSH levels significantly decreased ( 0.05), FSH, LH, T, AMH levels significantly decreased ( 0.05), with the greatest improvement and significantly better than selenium yeast group ( 0.05). CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats, reduce thyroid antibody titers, then act on the ovarian function, regulate hormone disorders, and alleviate the pathological damage of rat's ovarian tissues. The effect of high dose Buzhong Yiqi granule is the best. 10.19852/j.cnki.jtcm.20240203.008
A systematic review of combinatorial treatment with warming and invigorating drugs and levothyroxine for hypothyroidism caused by Hashimoto disease. Cheng Xiangwen,Wei Zixiao,Zhang Guangde,Shao Xin,Li Bo,Gao Rui Annals of translational medicine BACKGROUND:We used the systematic review method to evaluate the clinical efficacy and safety of combinatorial treatment with warming and invigorating drugs and levothyroxine on hypothyroidism caused by Hashimoto thyroiditis (HT). METHODS:We set inclusion and exclusion criteria, searched for studies using electronic databases and manual retrieval, selected studies according to the inclusion and exclusion criteria, and assessed the qualities of the included studies according to the Jadad scale. We performed a meta-analysis and analyzed the biases and sensitivities of the results using Revman 5.3 software. RESULTS:We retrieved 94 and 7 of the studies met the inclusion criteria. Warming and invigorating drugs and levothyroxine increased free triiodothyronine (FT3) and free thyroxine (FT4) levels and reduced thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) levels more than levothyroxine alone. However, the FT4 data were not stable. There were no statistically significant differences between the experimental and the control groups with regards to the effects on traditional Chinese medicine (TCM) syndromes and total therapeutic effects. There was insufficient evidence to make conclusions regarding TCM syndromes scores, goiter reduction, recurrence rate, and adverse reactions. CONCLUSIONS:Warming and invigorating drugs combined with levothyroxine may improve treatment of hypothyroidism caused by HT more than levothyroxine alone based on the FT3, FT4, TSH, TPOAb, and TGAb results. Based on the low qualities of the included studies, further evidence is needed to confirm these conclusions. 10.21037/atm.2016.12.16
Modulation of T-Bet and GATA-3 expression in experimental autoimmune thyroiditis rats through ginsenoside treatment. Chen Jie,Feng Xiaohong,Huang Qi Endocrine research Hashimoto's thyroiditis (HT) is one of the most common organ-specific autoimmune diseases. Increasing evidence indicates that HT may be characterized by an imbalance in the helper T cell subsets Th1 and Th2. Traditional Chinese Medicine (TCM) considers HT as a chronic exhaustion disease, leading to deficiency of qi. In TCM, qi indicates the functional power of the organs of the human body; hence TCM recommends focusing the treatment of HT so as to increase qi production. Ginseng is a well-known herbal medicine exhibiting a variety of efficacies, its main function-being to generate qi. Ginseng's principal active component is ginsenoside, and modern pharmacology has shown that ginsenoside demonstrates biphasic immunomodulatory effects that can be utilized for the treatment of immune disorders. Previous work demonstrated that ginsenoside has a therapeutic effect on HT, but its mechanism is unknown. Experimental autoimmune thyroiditis rats were produced in order to investigate whether ginsenoside can modulate Th1/Th2 imbalance, the direct objective being to examine modulation of IFN-γ and IL-4 by ELISA, and the gene and protein expression of T-bet and GATA-3 by real-time PCR and Western blot. IFN-γ levels were increased while IL-4 levels decreased in EAT rats; treatment with ginsenoside led to decreased peripheral blood IFN-γ levels, with low doses statistically significant. Ginsenoside produced a biphasic effect on IL-4, with low and moderate doses promoting and high doses inhibiting secretion. Both protein and mRNA levels of T-bet were markedly reduced, while GATA-3 was significantly increased by ginsenoside. 10.3109/07435800.2015.1066800
Anti-inflammatory effects of luteolin on experimental autoimmune thyroiditis in mice. Xia Nan,Chen Gang,Liu Min,Ye Xiaozhen,Pan Yahui,Ge Jiuyu,Mao Yanting,Wang Hongwei,Wang Jian,Xie Sijing Experimental and therapeutic medicine Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis. In the present study, the effect of luteolin on experimental autoimmune thyroiditis (EAT) was analyzed in C57BL/6 mice. Hematoxylin and eosin examination showed that luteolin attenuated lymphocytic infiltration and follicle destruction in thyroid glands. Immunohistochemistry results demonstrated that luteolin significantly reduced the phosphorylation of STAT3 within the thyroid. An study was carried out in a RAW264.7 macrophage cell line. Western blot findings demonstrated that luteolin significantly inhibited interferon-γ-induced increases in cyclooxygenase 2, phosphorylated STAT1 and phosphorylated STAT3 expression levels and the secretion of the proinflammatory cytokine tumor necrosis factor-α in supernatants. The present findings indicated that luteolin may exert potent anti-inflammatory effects on murine EAT, which may provide a novel therapeutic medication strategy for the early intervention of HT. 10.3892/etm.2016.3854
Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages. Journal of immunology (Baltimore, Md. : 1950) Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT. 10.4049/jimmunol.2300779
[Systematic review and trail sequential analysis of preparation of Xiakucao for Hashimoto's thyroiditis]. Zhang Yi-Liang,Hu Rui-Xue,Zhao Hui,Yang Wei,Yu Dan-Dan,Li Hui-Min,Liao Xing,Gu Hao Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica To systemically evaluate the clinical efficacy and safety of oral preparation of Xiakucao with levothyroxine(LT4) on Hashimoto's thyroiditis(HT), so as to provide the evidence for its clinical application in the future. All the included studies were retrieved from four Chinese databases and three English databases from their inception to December 2019. ROB assessment tool of cochrane system and the evidence classification recommended by GRADE were used to evaluate the quality of evidences in all included studies. RevMan 5.3 was used for Meta-analysis of the outcomes. Software TSA 0.9(trail sequential analysis) was used to estimate the sample size for Meta-analysis. The results showed that 11 randomized controlled trials and totaling 1 215 patients were included. Preparation of Xiakucao combined with LT4 was adopted as intervention in experimental group, while patients in control group were treated with LT4 alone. Meta-analysis results showed that as compared with control group, the rate of total efficacy in experimental group was significant improved, including improvement of thyroid function and thyroid autoantibodies, shrinkage of thyroid gland and nodule, and improvement of clinical symptoms such as fatigue and cold intolerance(RR=1.15, 95%CI[1.09, 1.21]). The experimental group significantly decreased the serum level of thyroperoxidase antibody TPO-Ab(SMD=-0.91, 95%CI[-1.40,-0.41]), and reduced the size of left thyroid lobe(MD=-1.46, 95%CI[-1.82,-1.11]), right thyroid lobe(MD=-1.45, 95%CI[-1.96,-0.94]) and isthmus of thyroid gland(MD=-1.08, 95%CI[-1.20,-0.95]). After evaluation based on GRADEpro, the results showed that the evidence quality of all included studies was low or very low. The result of TSA showed that the cumulative sample size had reached the expected value. However, the pooled results may be affected by one study with high bias risk, with not so high effect intensity of evidences. From this review, we can see that in treatment of HT, intervention of preparation of Xiakucao combined with LT4 has advantages on improvement of clinical efficiency, decreasing serum level of TPO-Ab and shrinkage of thyroid gland. However, due to the quality of evidence, more rigorously designed and high-quality trials are needed in the future to verify the clinical efficacy and safety of preparation of Xiakucao in treating HT. 10.19540/j.cnki.cjcmm.20200909.501
Effect of large dosage of Prunella on Hashimoto's thyroiditis: A protocol of systematic review and meta-analysis of randomized clinical trials. Medicine INTRODUCTION:Hashimoto's Thyroiditis (HT) is one of the common autoimmune diseases, which can lead to thyroid reduction, increase the risk of tumor, and seriously affect women's reproductive health. Many other autoimmune diseases are easy to occur, seriously harming people's health.large dose herb Prunella or compound prescription contain large dose Prunella for treatment of HT has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, it is necessary to carry out a systematic evaluation on Prunella and provide effective evidence for further research. METHODS AND ANALYSIS:The following databases will be searched from their inception to October 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure. MAIN RESULTS:serum thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TGAb), other results: serum thyroid stimulating hormone (TSH), serum free triiodothyronine (FT3), serum free thyroid hormone (FT4). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews (SR)of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS:The results of this study will systematically evaluate the efficacy and safety of large dose prunella salicorrhizae in the intervention of people with HT. CONCLUSION:The systematic review of this study will summarize the current published evidence of large dose prunella for the treatment of HT, which can further guide the promotion and application of it. ETHICS AND COMMUNICATION:This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.Open Science Fra mework (OSF) registration number:October 21, 2020.osf.io/fcyqp. (https://osf.io/fcyqp). 10.1097/MD.0000000000023391
Dioscin alleviates hashimoto's thyroiditis by regulating the SUMOylation of IRF4 to promote CD4CD25Foxp3 treg cell differentiation. Yongjun Cao,Nan Qiao,Yumeng Sun,Xiaowen Jin,Weibo Wen Autoimmunity Dioscin has been used as a treatment for Hashimoto's thyroiditis (HT) in China. However, the molecular mechanisms governing the modes of action of dioscin have not been elucidated. In this study, flow cytometry and Western blotting were used to identify the proportions of CD4CD25 regulatory T (Treg) cells and the expression of forkhead box P3 (Foxp3) and SUMO-specific protease 1 (SENP1) in HT patients' peripheral blood mononuclear cells (PBMCs). A pTg-induced rat model of HT was established by injection of 100 μg pTg. Then, the model rats were randomly divided into three groups ( = 5): control (NC), model (HT) and dioscin treatment. After oral administration of dioscin each day for two weeks, CD4CD25Foxp3 Treg cells were analysed by flow cytometry, and the protein expression levels of SENP1, Foxp3, SUMO-1 and SUMO-2/3 were measured by Western blotting. Co-immunoprecipitation (Co-IP) was used to identify the SUMOylation of interferon regulatory factor 4 (IRF4). The results showed that the proportions of CD4CD25 Treg cells and the expression of Foxp3 were significantly decreased in HT patients, but the expression of SENP1 was enhanced compared to healthy controls (HCs). However, compared to the pTg-induced HT rat group, the expression of Foxp3, SUMO-1, and SUMO-2/3 and the proportions of CD4CD25Foxp3 Treg cells were increased, whereas the expression of SENP1 was decreased, in the dioscin-treated group. Furthermore, the SUMOylation of IRF4 was increased after SENP1 was knocked down. The results of our study indicate that dioscin can promote the differentiation of the CD4CD25Foxp3 Treg cells and subsequently upregulate the SUMOylation of IRF4 by downregulating SENP1 expression. 10.1080/08916934.2020.1855428
Clinical efficacy of Bupleurum inula flower soup for immune damage intervention in Hashimoto's thyroiditis: A placebo-controlled randomized trial. Frontiers in pharmacology Antibody-mediated humoral immune response is involved in the damage process in Hashimoto's thyroiditis (HT). Although the traditional Chinese medicine (TCM) formula bupleurum inula flower soup (BIFS) is often used in HT treatment, it has not been evaluated through high-quality clinical research. Rigorously designed randomized, double-blind, prospective clinical studies are urgently needed to evaluate BIFS for intervening in the HT immune damage process, and to improve clinical prognosis and patient quality of life. A prospective randomized, double-blind, placebo-controlled trial was used to evaluate the efficacy of BIFS. Fifty participants diagnosed with HT with hypothyroidism were randomly assigned at a 1:1 ratio to the BIFS (levothyroxine with BIFS) or control (levothyroxine with placebo) group. Participants received 8 weeks of treatment and were followed for 24 weeks. They were monitored for: levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid stimulating hormone (TSH); scores for depression, anxiety, and health-related quality of life (HRQoL); thyroid volume; safety indicators including routine blood tests, liver and kidney functions, and electrocardiogram; and levothyroxine dose. Forty-eight participants completed the study and were included in the final analysis. At baseline, there were no significant between-group differences in the observed indicators ( > 0.05). Post-treatment, compared with the control group, the BIFS group had significantly lower levels of TPOAb (275.77 ± 132.98 vs. 441.78 ± 195.50, = 0.001), TgAb (385.92 ± 281.91 vs. 596.17 ± 282.26, = 0.013), and TSH (6.57 ± 3.73 vs. 9.63 ± 5.34, = 0.001). Compared with the control group, the BIFS group's scores improved significantly for depression (47.00 ± 5.12 vs. 51.04 ± 3.22, = 0.002), anxiety (43.21 ± 4.22 vs. 48.08 ± 2.81, = 0.005), and HRQoL physical (62.08 ± 5.97 vs. 57.96 ± 4.71, = 0.011) and psychological (60.17 ± 5.94 vs. 55.75 ± 7.09, = 0.024) subscores. At 24-week follow-up, levothyroxine combined with TCM allowed a significantly reduced levothyroxine dose (0.58 ± 0.43 vs. 1.02 ± 0.45, = 0.001). The post-treatment clinical efficacy rates differed significantly ( = 0.03), with 75% (18/24) for the BIFS group and 46% (11/24) for the control group. There were no significant between-group differences in thyroid volume or safety indicators after eight treatment weeks or at the 24-week follow-up ( > 0.05). The TCM BIFS can effectively reduce thyroid titer, relieve clinical and emotional symptoms, and improve HRQoL in patients with HT. https://www.chictr.org.cn/, identifier ChiCTR1900020987. 10.3389/fphar.2022.1049618
Mechanism of Xiaoying Daotan decoction in treating Hashimoto's thyroiditis based on the Notch/Treg/Th17 pathway. Annals of translational medicine BACKGROUND:The study created mice model of Hashimoto's thyroiditis (HT) and induced thyroid inflammatory cell lines, exploring the mechanism of Xiaoying Daotan decoction on HT. METHODS:Divided HT mice models into model group (0.2 mL saline), Western medicine group (0.2 mL levothyroxine sodium tablets), traditional Chinese medicine group (0.2 mL Xiaoyin Daotan prescription), and Notch protein inhibition group (0.2 mL Xiaoyin Daotan prescription). After treatment, serum Notch protein expression and T cell (Treg)/T helper cell 17 (Th17) cytokines levels were detected through Enzyme linked immunosorbent assay (ELISA). Use real-time qualitative polymerase chain reaction detected Notch protein expression. Thyroid inflammatory cell lines were induced and divided into 5 groups: blank group, iNotch group (knocking down the Notch protein gene of thyroid inflammatory cells), NC group (Notch protein carrier negative control group), iNotch + DS group and DS group (knocking down the Notch protein gene of thyroid inflammatory cells). The cells were treated with serum containing Xiaoying Daotan decoction. After culture, detected Notch protein expression level and Treg/Th17 cytokine level in each group. RESULTS:For the animal experiment, the serum Notch protein expression, the serum levels of key activating proteins Signal Transducer and Activator of Transcription 3 (STAT3), RAR-related orphan receptor gamma T (RORγt), and interleukin (IL)-22 of Th17 cells of mice in the model group was significantly higher than that of the other groups. Compared with the model group and Western medicine group, the serum transforming growth factor-β (TGF-β) level of the mice in the traditional Chinese medicine group and the Notch protein inhibition group was significantly higher. All the differences were statistically significant (P<0.05). For the cell experiment, the β-actin value of Notch protein in thyroid inflammatory cell genes was significantly downregulated and the key activation protein of Treg was significantly upregulated in iNotch + DS group and DS group compared with the other 3 groups. Levels of Th17 key activating proteins STAT3, IL-17, and IL-22 in the iNotch group, iNotch + DS group, and DS group were lower than those of the blank group and NC group, both with statistically significant difference (P<0.001). CONCLUSIONS:The mechanism of Xiaoying Daotan decoction on HT could be related to the immune inflammatory response of the Treg/Th17 cell axis mediated by the Notch protein pathway. 10.21037/atm-21-6253
Network Pharmacology Studies on the Molecular Mechanism of Hashimoto's Thyroiditis Treated with Shutiao Qiji Decoction. Combinatorial chemistry & high throughput screening BACKGROUND:In recent years, the number of patients with Hashimoto's thyroiditis has been increasing, and traditional Chinese medicine ingredients and combinations have been applied to treat Hashimoto's thyroiditis to increase efficacy and reduce side effects during the treatment process. OBJECTIVE:Shutiao Qiji Decoction is one of the Chinese traditional medicine prescriptions, which is commonly used to treat cancer, tumor, etc. It is also used for thyroid-related diseases in the clinic. Hashimoto's thyroiditis is an autoimmune disease. In this study, the mechanism of Shutiao Qiji Decoction in treating Hashimoto's thyroiditis was studied through network pharmacology and molecular docking verification. METHOD:Each Chinese medicine ingredient of Shutiao Qiji Decoction was retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The related genes of HT were searched from the UniProt and GeneCards databases. Meanwhile, we used Cytoscape to construct the protein-protein interaction (PPI) visual network analysis, and used the search tool to search the database of Interacting Genes (STRING) to build a PPI network. These key proteins were enriched and analyzed by molecular docking validation, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hashimoto's thyroiditis disease model was established in SD rats, and SQD was administered by gavage after the successful establishment of the model. After 6 weeks of continuous administration of the drug by gavage, tissue samples were collected and the thyroid and spleen tissues were visualized by HE staining to verify the therapeutic effect. RESULTS:The results showed that there were 287 TCM active ingredients, 1920 HT-related disease targets, and 176 drug and disease targets in SQD. Through PPI analysis, GP analysis, and KEGG analysis of the common targets of drugs and diseases, we found their pathways of action to be mainly cancer action pathway, PI3K-AKT signaling pathway, and T-cell action pathway. The active ingredients of the drugs in SQD, malvidin, stigmasterol, porin-5-en-3bta-ol, and chrysanthemum stigmasterol, were docked with the related target proteins, MAPK, GSK3β, TSHR, and NOTCH molecules. The best binding energies obtained from docking were mairin with TSHR, stigmasterol with TSHR, poriferast-5-en-3beta-ol with MAPK, and chryseriol with GSK3β, with binding energies of -6.84 kcal/mol, -6.53 kcal/mol, -5.03 kcal/mol, and -5.05 kcal/mol, respectively. HE staining sections of rat thyroid and spleen tissues showed that SQD had a therapeutic effect on Hashimoto's thyroiditis and restored its immune function. CONCLUSION:It is verified by molecular docking results that Shutiao Qiji Decoction has a potential therapeutic effect on Hashimoto's thyroiditis in the MAPK/TSHR/NOTCH signal pathway, and that the main components, mairin, stigmasterol, poriferast-5-en-3beta-ol, and chryseriol play a role in it. SQD has been shown to have a good therapeutic effect on Hashimoto's thyroiditis. 10.2174/0113862073259714231012070100
Clinical efficacy and molecular mechanism of Chinese medicine in the treatment of autoimmune thyroiditis. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. AIM OF THE STUDY:The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. MATERIALS AND METHODS:The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. RESULTS:An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. CONCLUSIONS: The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways. 10.1016/j.jep.2023.117689
Efficacy of Chinese medicine in the adjuvant treatment of Hashimoto's thyroiditis with hypothyroidism: a systematic review and meta-analysis. Biotechnology & genetic engineering reviews The quality of the studies was assessed using the Cochrane risk bias assessment tool and the results were analyzed using Review Manager 5.3 software. The evidence was also evaluated for its strength using GRADE. A total of 18 randomized controlled trials were included in the study, involving 1247 patients. The primary outcomes of this study included overall efficacy, effectiveness in treating specific symptoms, and the Traditional Chinese Medicine symptom score. The secondary outcomes included the levels of FT3, FT4, and TSH, the size of the thyroid gland, and any adverse events. The results of the meta-analysis showed that CHM combined with WM has a better curative effect and a more effective reduction in clinical symptoms than WM alone: comprehensive efficacy [OR = 4.83; 95% CI (3.45, 6.76)], syndrome efficacy [OR = 5.95; 95% CI (3.94, 8.99)], TCM symptom score SMD = -1.49; 95% CI (-1.86, -1.11)], FT3 [SMD = 0.59; 95% CI (0.48, 0.71)], FT4 [SMD = 0.59; 95% CI (0.48, 0.71)], TSH SMD = -0.97; 95% CI (-1.35, -0.58)], and thyroid volume SMD = -0.25; 95% CI (-0.34, 0.15)]. The incidence of adverse events between the groups was not significantly different [OR = 1.00; 95% CI (0.14, 7.27)]. Because of the effectiveness of CHM, we support using CHM to improve clinical efficacy in the treatment of HTH. The results of our research suggest that the use of Chinese Herbal Medicine (CHM) in combination with Western Medicine (WM) may result in improved clinical efficacy in the treatment of hypothyroidism (HTH) compared to using WM alone. 10.1080/02648725.2023.2184959
Herbal medicine for Hashimoto's thyroiditis: A systematic review and network meta-analysis. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Conventional treatments for Hashimoto's thyroiditis (HT) are limited. Herbal medicines (HM) are considered a potential intervention for the treatment of HT. AIM OF THE STUDY:This study aimed to investigate the efficacy and safety of HM for HT. MATERIALS AND METHODS:A Bayesian network meta-analysis was conducted for patients with HT in randomized controlled trials identified in PubMed, Cochrane Library, Web of Science, EMBASE, Chinese Clinical Trial Registry (Chi CTR), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (the VIP), China Chinese Biomedical Database (CBM), and Wanfang Database were searched from their inception to Oct 1, 2022. Outcomes included the primary outcome (TPOAb), secondary outcomes (TSH, TGAb, FT3, FT4, and traditional Chinese medicine symptom scores), and adverse events. This study was registered in PROSPERO (CRD42022363640). RESULTS:Sixteen trials were reviewed and 16 HM formulae were compared. Compared with non-drug therapy (NDT), all therapies, except for Tiaoqi-Qingjie Therapy, reduced the primary outcome of TPOAb with different levels of effectiveness, ranging from 0.01 (95%CI 0.00, 0.02) to 0.92 (95%CI 0.56, 1.53). Ranking probability analysis indicated that Yiqi Huayu Recipe, Liqi Xiaoying decoction, and Shugan Sanjie therapy reduced thyroid antibody levels the most, including TPOAb (100.0%, 90.9%, and 90.3%, respectively) and TGAb (98.3%, 94.4%, and 87.3%, respectively). All HMs displayed a significant effect on the TCM Symptom score and possibly benefitted the treatment of HT, ranging from 6.62 (95% CI 2.06, 21.24) to 94.50 (95% CI 15.97, 559.14). No serious adverse events were reported. CONCLUSIONS:Herbal medicines may be effective in the treatment of HT, especially in reducing thyroid antibody levels and improving clinical symptoms without affecting thyroid function. However, these results should be considered preliminary and further verified using high-quality evidence. 10.1016/j.jep.2023.117663
Therapeutic effect of mesenchymal stem cell on Hashimoto's thyroiditis in a rat model by modulating Th17/Treg cell balance. Cao Yongjun,Jin Xiaowen,Sun Yumeng,Wen Weibo Autoimmunity The autoimmune condition Hashimoto's thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto's thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells - an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto's thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto's thyroiditis. 10.1080/08916934.2019.1697689
Thyroid hemiagenesis and Hashimoto's thyroditis-diagnostic and treatment pitfalls. Wang Minghao,Hou Lingmi,Chen Maoshan,Ren Lin,Tang Peng,Zhang Yi,Jiang Jun World journal of surgical oncology BACKGROUND:Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis. CASE PRESENTATION:A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis. Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery. CONCLUSIONS:Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment. 10.1186/s12957-017-1250-0
Hashimoto's thyroiditis and coexisting disorders in correlation with HLA status-an overview. Wiener medizinische Wochenschrift (1946) Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a frequent disorder of the thyroid gland caused by autoimmune-trigged lymphocytic infiltration and destruction of the thyroid gland. With the progressive destruction of the organ, the thyroid gland shrinks in size, thus commonly leading to hypothyroidism. Therapy of HT is mainly focused on managing the thyroid dysfunction by oral substitution of L‑thyroxine. However, patients with HT often complain about a broad spectrum of symptoms, with some of them hardly explained by HT itself. Several other disorders are known to be associated with HT. The etiology of HT seems to be multifactorial, including environmental influences such as iodine supply, infections, and stress as triggers of immune modulation. In addition, also a genetic background based on changes of the human leukocyte antigen (HLA) status seems to be evident. The paper will provide an overview of diseases related to HT, including their correlation to certain HLA patterns. This presentation should give a broader view on HT-related disorders and facilitate detailed examination and management of patients with HT. 10.1007/s10354-021-00879-x
Influence of Hashimoto thyroiditis on diagnosis and treatment of thyroid nodules. Frontiers in endocrinology Background:As the prevalence of Hashimoto's thyroiditis (HT) and thyroid cancer (TC) has been increasing dramatically in recent years, the association between the two diseases has been widely debated and studied. However, no consistent findings are available and the relationship remains controversial. In this study, we analyzed the influence of HT on the diagnosis and treatment of thyroid nodules and investigated the relationship between HT and TC. Methods:From Jan 2017 to Apr 2021, 4678 patients underwent thyroid surgery were collected. Of these patients, 440 were diagnosed with HT (242 nodular goiter (NG) with HT, 198 TC with HT). These patients were grouped when appropriate and the data from these patients were statistically analyzed by using SPSS and GraphPad Prism 6. Results:HT occurred in 198 of 1089 (18.2%) TC patients and 242 of 3589 (6.74%) patients without TC (=0.000). In terms of the ultrasonography features, in the NG with HT group, 33.1% (80/242) of patients had fine calcification and 45.9% (111/242) of patients whose TI-RADS classification were > Level 3. In the isolated PTC group, 32.3% (2343/7260) LN were metastasis-positive while in the NG with HT group, only 26.0% (504/1939) LN were metastasis-positive (=0.000). The proportion of PTMC was significantly higher (=0.000), while the proportion of multifocal carcinoma was significantly lower when coexisting with HT (=0.029). When comparing the data from the two groups diagnosed as PTMC coexisting with HT or not, there was no significant difference in the composition ratio of tumor number, LN metastasis, LN dissection area, regional LN metastasis and number of negative/positive LN (=0.614, =0.051, =0.139, =0.350, =1.000 and =0.333 respectively). In the MPTC group, 42.2% (872/2065) LN were metastasis-positive while in the MPTC with HT group, only 23.6% (50/212) LN were metastasis-positive (=0.000). Conclusions:Our data suggested that HT is associated with an increased risk of developing TC but may be a protective factor against PTC progression and metastasis. The coexistence of HT affects the judgment of thyroid nodules by ultrasonography. 10.3389/fendo.2022.1067390
Autoimmunity, New Potential Biomarkers and the Thyroid Gland-The Perspective of Hashimoto's Thyroiditis and Its Treatment. International journal of molecular sciences Autoimmune thyroid disease (AITD) is the most common organic specific illness of the thyroid gland. It may manifest as the overproduction or the decline of thyroxine and triiodothyronine. Hyperthyroidism develops due to the overproduction of hormones as an answer to the presence of stimulatory antibodies against the TSH receptor. Hashimoto's thyroiditis (HT) is generally characterized by the presence of thyroid peroxidase and thyroglobulin antibodies, with a concomitant infiltration of lymphocytes in the thyroid. Due to the progressive destruction of cells, AITD can lead to subclinical or overt hypothyroidism. Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development. Due to increasing incidence and social awareness of this pathology, there is an urgent need to expand the background concerning AITD. A growing body of evidence suggests possible ways of treatment apart from traditional approaches. Simultaneously, the role of potential new biomarkers in the diagnosis and monitoring of AITD has been highlighted recently, too. Therefore, we decided to review therapeutic trends in the course of AITD based on its pathophysiological mechanisms, mainly focusing on HT. Another aim was to summarize the state of knowledge regarding the role of new biomarkers in this condition. 10.3390/ijms25094703
Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Ragusa Francesca,Fallahi Poupak,Elia Giusy,Gonnella Debora,Paparo Sabrina Rosaria,Giusti Claudia,Churilov Leonid P,Ferrari Silvia Martina,Antonelli Alessandro Best practice & research. Clinical endocrinology & metabolism Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disorders (AITDs), is the leading cause of hypothyroidism in the iodine-sufficient areas of the world. About 20-30% of patients suffers from HT, whose cause is thought to be a combination of genetic susceptibility and environmental factors that causes the loss of immunological tolerance, with a consequent autoimmune attack to the thyroid tissue and appearance of the disease. The pathologic features of lymphocytic infiltration, especially of T cells, and follicular destruction are the histological hallmark of autoimmune thyroiditis (AIT), that lead to gradual atrophy and fibrosis. An important role in the immune-pathogenesis of AITDs is due to chemokines and cytokines. In about 20% of patients, AITDs are associated with other organ specific/systemic autoimmune disorders. Many studies have demonstrated the relationship between papillary thyroid cancer and AITD. The treatment of hypothyroidism, as result of AIT, consists in daily assumption of synthetic levothyroxine. 10.1016/j.beem.2019.101367
Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Ralli Massimo,Angeletti Diletta,Fiore Marco,D'Aguanno Vittorio,Lambiase Alessandro,Artico Marco,de Vincentiis Marco,Greco Antonio Autoimmunity reviews Hashimoto's thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully elucidated, Hashimoto's thyroiditis is related to an interaction among genetic elements, environmental factors and epigenetic influences. Cellular and humoral immunity play a key role in the development of the disease; thus, a T and B cells inflammatory infiltration is frequently found. Histopathologic features of the disease include lymphoplasmacytic infiltration, lymphoid follicle formation with germinal centers, and parenchymal atrophy. Moreover, the occurrence of large follicular cells and oxyphilic or Askanazy cells is frequently associated to Hashimoto's thyroiditis. Clinically, Hashimoto's thyroiditis is characterized mainly by systemic manifestations due to the damage of the thyroid gland, developing a primary hypothyroidism. Diagnosis of Hashimoto's thyroiditis is clinical and based on clinical characteristics, positivity to serum antibodies against thyroid antigens (thyroid peroxidase and thyroglobulin), and lymphocytic infiltration on cytological examination. The mainstream of treatment is based on the management of the hypothyroidism with a substitution therapy. A relationship between Hashimoto's thyroiditis and a possible malignant transformation has been proposed in several studies and involves immunological/hormonal pathogenic links although specific correlation is still debated and needs to be further investigated with prospective studies. 10.1016/j.autrev.2020.102649
Global prevalence and epidemiological trends of Hashimoto's thyroiditis in adults: A systematic review and meta-analysis. Frontiers in public health Objective:Although Hashimoto's thyroiditis is associated with cardiovascular disease and malignancy, the global status of Hashimoto's thyroiditis is not well characterized across regions. Our objective was to evaluate the prevalence and trends of Hashimoto's thyroiditis in adults in regions with different economic income levels around the world. Methods:For this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science databases, and 48 random-effects representative studies from the inception to June 2022 were included without language restrictions to obtain the overall prevalence of Hashimoto's thyroiditis in adults worldwide. In addition, we stratified by time of publication, geographic region, economic level of the region of residence, gender, diagnostic method, etc. Results:A total of 11,399 studies were retrieved, of which 48 met the research criteria: 20 from Europe, 16 from Asia, five from South America, three from North America, and three from Africa. Furthermore, there are two projects involving 19 countries and 22,680,155 participants. The prevalence of Hashimoto's thyroiditis was 7.5 (95%CI 5.7-9.6%), while in the low-middle-income group the prevalence was 11.4 (95%CI 2.5-25.2%). Similarly, the prevalence was 5.6 (95%Cl 3.9-7.4%) in the upper-middle-income group, and in the high-income group, the prevalence was 8.4 (95%Cl 5.6-11.8). The prevalence of Hashimoto's varied by geographic region: Africa (14.2 [95% CI 2.5-32.9%]), Oceania (11.0% [95% CI 7.8-14.7%]), South America and Europe 8.0, 7.8% (95% Cl 0.0-29.5%) in North America, and 5.8 (95% Cl 2.8-9.9%) in Asia. Although our investigator heterogeneity was high (I), our results using a sensitivity analysis showed robustness and reliability of the findings. People living in low-middle-income areas are more likely to develop Hashimoto's thyroiditis, while the group in high-income areas are more likely to develop Hashimoto's thyroiditis than people in upper-middle-income areas, and women's risk is about four times higher than men's. Conclusions:Global Hashimoto's thyroiditis patients are about four times as many as males, and there are discrepancies in the regions with different economic levels. In low-middle-income areas with a higher prevalence of Hashimoto's thyroiditis, especially countries in Africa, therefore local health departments should take strategic measures to prevent, detect, and treat Hashimoto's thyroiditis. At the same time, the hidden medical burden other diseases caused by Hashimoto's thyroiditis should also be done well. Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022339839. 10.3389/fpubh.2022.1020709
Parvovirus B19 infection associated with Hashimoto's thyroiditis in adults. Wang Juanhong,Zhang Weiping,Liu Hongxiang,Wang Di,Wang Wenqing,Li Yuanfei,Wang Zhe,Wang Lu,Zhang Wei,Huang Gaosheng The Journal of infection OBJECTIVE:Parvovirus B19 is a common human pathogen, which has been linked to autoimmune diseases recently. The aim of the study is to evaluate whether B19 is involved in adult Hashimoto's thyroiditis (HT). METHODS:Eighty-six thyroid tissues from the adult patients with a spectrum of thyroid disorders were examined for B19 DNA and capsid protein by nested PCR, in-situ hybridization and immunohistochemistry. The presence of viral DNA in HT epithelium was studied by laser-capture microdissection and sequencing of PCR products. The expressions of nuclear factor-kappaB (NF-kappaB) and interleukin-6 were investigated by immunohistochemistry. RESULTS:B19 DNA was significantly present in HT tissues by both PCR (29/32, 90.6%) and in-situ hybridization (23/32, 71.9%, all p < 0.01) compared with normal thyroid tissue (7/16, 43.8%; 2/16, 12.5%). Laser-capture microdissection further confirmed this difference. B19 capsid protein in HT group was significantly higher than that in all the control groups (p < 0.01), and the expression of NF-kappaB and interleukin-6 in HT tissues was up-regulated. NF-kappaB was well co-localized with B19 protein in thyroid epithelia by double-labeling immunofluorescence and confocal microscopy. CONCLUSIONS:The presence of B19 nuclear acid and viral protein was significantly common in HT tissues and it suggested a possible role of B19 in adult HT. 10.1016/j.jinf.2010.02.006
Bioinformatics and Connectivity Map Analysis Suggest Viral Infection as a Critical Causative Factor of Hashimoto's Thyroiditis. International journal of molecular sciences Hashimoto's thyroiditis (HT) is a common autoimmune disease, and its prevalence is rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed the features of HT through bioinformatics analysis so as to identify the markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG-pathway-enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed a Gene Set Enrichment Analysis (GSEA) by using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, a connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with the general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. The GSEA results revealed activation of autoimmune-disease-related pathways and several viral-infection pathways. Autoimmune-disease and viral-infection pathways were highly interconnected by common genes, while the HLA genes, which are shared by both, were significantly upregulated. The CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor which responds to viral activity, might serve as potential marker of HT. 10.3390/ijms24021157
Could there be an association between Hashimoto's thyroiditis and demodex infestation? Journal of cosmetic dermatology BACKGROUND:Human demodex mites are parasites that live in the pilosebaceous unit and can result in the disease demodicosis. While demodicosis may occur as a primary skin disease; immunosuppression, and topical or systemic immunosuppressive treatments can cause secondary demodicosis. It is known that thyroid hormones may cause skin changes, such as xerosis, and thereby may also modulate immune responses in the skin. OBJECTIVES:The aim of this study is to investigate whether or not that the changes occurring in the skin of patients with Hashimoto's Thyroiditis (HT) predispose to demodex infestation. METHODS:Seventy-eight patients being followed for a diagnosis of HT at Kocaeli University Endocrinology Outpatient Clinic, between January 2019 and March 2020, constituted the patient group. The control group consisted of 41 patients who did not have any chronic systemic or dermatological disease and were shown to have no thyroid disease by laboratory tests. Demodex intensity in the malar regions of the patient and control groups was determined using the standardized skin surface biopsy (SSSB) method and compared with each other. RESULTS:HT patients were significantly more likely to have increased demodex density and suggestive SSSB results than the controls (p < 0.001, p = 0.012, respectively). A significant correlation was found between demodex intensity and the findings of xerosis (p = 0.010, p = 0.011) and spiny follicular papules (p = 0.008, p = 0.008) in the patient or control groups, respectively. However, a significant correlation was identified between the demodex density and the symptoms of burning-stinging (p = 0.028), and feelings of dryness (p = 0.018) roughness (p = 0.028) only in the control group. CONCLUSION:Xerotic skin and/or impaired immune responses as a result of autoimmune changes in patients with HT may lead to secondary demodicosis. 10.1111/jocd.15005
The microbiota and autoimmunity: Their role in thyroid autoimmune diseases. Köhling Hedda L,Plummer Sue F,Marchesi Julian R,Davidge Kelly S,Ludgate Marian Clinical immunology (Orlando, Fla.) Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject. 10.1016/j.clim.2017.07.001
UV radiation and air pollution as drivers of major autoimmune conditions. Environmental research Autoimmune diseases comprise a very heterogeneous group of disorders characterized by disruptive immune responses against self-antigens, chronic morbidity and increased mortality. The incidence and prevalence of major autoimmune conditions are particularly high in the western world, at northern latitudes, and in industrialized countries. This study will mainly focus on five major autoimmune conditions, namely type 1 diabetes, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, and autoimmune thyroid disorders. Epidemiological and experimental evidence suggests a protective role of sunlight exposure on the etiology of major autoimmune conditions mediated by the endogenous production of vitamin D and nitric oxide. A historical perspective shows how the rise of anthropogenic air pollutants is temporally associated with dramatic increases in incidence of these conditions. The scattering caused by ambient particulate matter and the presence of tropospheric ozone can reduce the endogenous production of vitamin D and nitric oxide, which are implicated in maintaining the immune homeostasis. Air pollutants have direct detrimental effects on the human body and are deemed responsible of an increasingly higher portion of the annual burden of human morbidity and mortality. Air pollution contributes in systemic inflammation, activates oxidative pathways, induces epigenetic alterations, and modulates the function and phenotype of dendritic cells, Tregs, and T-cells. In this review, we provide epidemiological and mechanistic insights regarding the role of UV-mediated effects in immunity and how anthropic-derived air pollution may affect major autoimmune conditions through direct and indirect mechanisms. 10.1016/j.envres.2023.115449
Modifiable risk factors for thyroid cancer: lifestyle and residence environment. Endokrynologia Polska In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer. 10.5603/ep.97258
Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors. Park Jun,Park Hyunju,Kim Tae Hyuk,Kim Sun Wook,Jang Hye Won,Chung Jae Hoon Frontiers in endocrinology Background:Although the incidence of thyroid cancer had been increasing until a few years ago, a decrease has been observed in the last years, probably due to the reduction of the screening tests in Korea. Childhood thyroid cancer has been increasing in the past with the same trend as in adults, but there have been few reports on recent trends. We analyzed the trends of thyroid cancer in Korean children and related factors. Methods:From national statistics and cancer register database, the data of age-specific incidence rate in Korean childhood thyroid cancer from 1999 to 2017 was obtained, and levels of seaweed intake, the number of computed tomography (CT) and neck ultrasonography (US), obesity prevalence rate, and smoking and alcohol consumption rates in children were analyzed. Results:The age-specific incidence of thyroid cancer in Korean children has increased in both genders between 1999 and 2017 (2.0 in 1999 vs. 7.2 in 2017, per population of 100,000), especially in the age group of 14-18 years (1.5 in 1999 vs. 5.5 in 2017, per population of 100,000). During the same period, levels of seaweed intake, number of CT scans and neck US, and prevalence of obesity in children increased significantly, while childhood smoking and alcohol consumption rates decreased. Conclusion:Unlike the adult thyroid cancer in Korea, childhood thyroid cancer continues to increase, and the cause might be accompanied by actual increases due to the environmental factors such as excessive iodine intake, exposure to medical radiation, and increased obesity prevalence as well as the screening effect. 10.3389/fendo.2021.681148
Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism. Erdal Muhammed,Sahin Mustafa,Hasimi Adnan,Uckaya Gökhan,Kutlu Mustafa,Saglam Kenan Biological trace element research The present study was conducted to evaluate the serum copper, zinc, magnesium, and selenium levels in patients with subclinical hypothyroidism in the iodine-rich region of Ankara, Turkey. The effects of hormone replacement therapy on these elements were also studied in these patients. Basal levels of selenium and iron in patients were significantly lower than control group (67.7 +/- 10.4 vs. 83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03 microg/dl). Serum magnesium levels were significantly higher in patient group (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in patients with selenium levels <80 microg/l (n = 31) was significantly higher than hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0; 1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace elements have changed after euthyroidism in patients with SH when compared to pretreatment levels. Selenium deficiency may contribute to cardiovascular disease risk in these patients. 10.1007/s12011-008-8117-8
Minerals: An Untapped Remedy for Autoimmune Hypothyroidism? Khan Seyad Zulficar Ali,Lungba Rayan M,Ajibawo-Aganbi Uvie,Veliginti Swathi,Perez Bastidas Maria V,Saleem Sania,Cancarevic Ivan Cureus For decades, the focus of managing autoimmune hypothyroidism has been on thyroxine replacement. Correcting lab parameters such as thyroid stimulating hormone (TSH) has been a primary goal. The increasing prevalence of Hashimoto's thyroiditis (HT) continues to impact the quality of life in patients. We believe a holistic approach to this disease entity, considering its underlying complex etiopathogenesis, would benefit patients. Nutraceuticals are combinations of essential nutrients and are becoming a part of novel medical treatments despite the lack of regulation. This review aims to present a concise summary of recent developments regarding minerals such as zinc, selenium, magnesium, iron, and their potential clinical benefit as nutraceuticals in patients with HT. We have explored the potential benefits and associations of these minerals in HT and thyroid function. We reviewed relevant articles, metanalyses, and clinical trials in literature platforms such as PubMed, PubMed Central, and Google Scholar. Significant data found in the literature suggesting a potential health benefit of these minerals in HT though there were many studies to the contrary. Many trials demonstrated the restoration of residual symptoms, reversal of HT-associated thyroid morphological changes, and improvement in thyroid functions. Many of these trials lack statistical power due to the small sample sizes, and their external validity may be questionable due to unaccounted confounding factors. In our opinion, to support an evidence-based holistic clinical approach, further scientific evidence is needed. The association of these elements in thyroid function necessitates more large scale pragmatic trials to elucidate the benefits of nutraceuticals in HT. 10.7759/cureus.11008
Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Frontiers in endocrinology Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto's thyroiditis (HT), Graves' disease (GD), Graves' ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out. 10.3389/fendo.2023.1225494
Urban Air Pollution Associated with the Incidence of Autoimmune Thyroid Diseases. Medical archives (Sarajevo, Bosnia and Herzegovina) Background:Endocrine disrupting air pollutants such as sulphur dioxide (SO), carbon monoxide (CO), nitrogen dioxide (NO), fine particle matter (PM), and ozone (O) can affect thyroid gland function on the level of synthesis, metabolism, and the action of its hormones. Objective:The aim of this study was to establish whether increased air pollution could contribute to an increased incidence of autoimmune thyroid diseases (AITD). Methods:A retrospective analysis was conducted of the medical records of 82000 patients at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. The target group of this study comprised a total of 174 patients from the Lukavac area. Daily data on concentrations of air pollutants were collected from the air quality monitoring station located in Lukavac. The study covered the period from 2015 to 2020. Results:The results of the monitoring confirmed the presence of air pollutants in concentrations above the permitted limits throughout the entire observed period. Concentrations of PM, SO, NO, CO, and O were in the range of 1.90-431.40 μg/m, 3.60-620.50 μg/m, 3.40-66.20 μg/m, 48.00-7002.00 μg/m, and 0.70-89.40 μg/m, with means of 64.08 μg/m, 77.48 μg/m, 22.57 μg/m, 1657.15 μg/m, and 31.49 μg/m, respectively. During the six-year period, 174 cases of AITD were registered, of which 150 (86.21%) were women and 24 (13.79%) men. Hashimoto's thyroiditis was found in 33 patients (18.97%), whilst 141 patients (81.03%) were diagnosed with atrophic thyroiditis. The highest total incidence of autoimmune thyroiditis was recorded in 2017, when it reached 99.49, 95% CI. Conclusion:The effects of chronic exposure to a mixture of air pollutants on the function of the thyroid gland are still not sufficiently well-known, but the numerical tendency towards a higher incidence of AITD in this study, albeit without statistical significance (p>0.05), still underlines the need for additional research. 10.5455/medarh.2022.76.115-121
Oxidative stress markers, trace elements, and endocrine disrupting chemicals in children with Hashimoto's thyroiditis. Sur Unzile,Erkekoglu Pinar,Bulus Ayse Derya,Andiran Nesibe,Kocer-Gumusel Belma Toxicology mechanisms and methods In this study, we aimed to investigate whether bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) exposure have any association with Hashimoto's thyroiditis (HT) and its biomarkers and to determine whether oxidative stress biomarkers and trace element levels showed any alterations in children with HT. We found that superoxide dismutase and glutathione peroxidase activities are lower in HT group from control (24% and 46%, respectively,  < 0.05). Zinc levels were significantly lower in HT group vs. control. In addition, the levels of mono-(2-ethylhexyl) phthalate (MEHP) which is the primary metabolite for DEHP, were markedly higher in HT group compared to control ( < 0.05). A negative correlation was observed between urinary BPA levels and fT4. In children with HT, oxidant/antioxidant balance is changed and these differences may be related by EDC exposure, the importance of which should be elucidated with further studies. 10.1080/15376516.2019.1646367
Hashimoto's thyroiditis, iron, and vitamin D deficiency among Egyptian female patients: associations and possible causalities. Salem Tarek M,Abdelmonem Esmail,Fayad Amira Hormones (Athens, Greece) 10.1007/s42000-021-00297-z
Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Rayman Margaret P The Proceedings of the Nutrition Society Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health. 10.1017/S0029665118001192
Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis. Hu Shiqian,Rayman Margaret P Thyroid : official journal of the American Thyroid Association BACKGROUND:Hashimoto's thyroiditis (HT) is considered to be the most common autoimmune disease. It is currently accepted that genetic susceptibility, environmental factors, and immune disorders contribute to its development. With regard to nutritional factors, evidence implicates high iodine intake and deficiencies of selenium and iron with a potential relevance of vitamin D status. To elucidate the role of nutritional factors in the risk, pathogenesis, and treatment of HT, PubMed and the Cochrane Library were searched for publications on iodine, iron, selenium, and vitamin D and risk/treatment of HT. SUMMARY:Chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly iodinated thyroglobulin (Tg) is more immunogenic. Recent introduction of universal salt iodization can have a similar, though transient, effect. Selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases protect the thyroid by removing excessive hydrogen peroxide produced for Tg iodination. Genetic data implicate the anti-inflammatory selenoprotein S in HT risk. There is evidence from observational studies and randomized controlled trials that selenium/selenoproteins can reduce thyroid peroxidase (TPO)-antibody titers, hypothyroidism, and postpartum thyroiditis. Iron deficiency impairs thyroid metabolism. TPO, the enzyme responsible for the production of thyroid hormones, is a heme (iron-containing) enzyme which becomes active at the apical surface of thyrocytes only after binding heme. HT patients are frequently iron deficient, since autoimmune gastritis, which impairs iron absorption, is a common co-morbidity. Treatment of anemic women with impaired thyroid function with iron improves thyroid-hormone concentrations, while thyroxine and iron together are more effective in improving iron status. Lower vitamin D status has been found in HT patients than in controls, and inverse relationships of serum vitamin D with TPO/Tg antibodies have been reported. However, other data and the lack of trial evidence suggest that low vitamin D status is more likely the result of autoimmune disease processes that include vitamin D receptor dysfunction. CONCLUSIONS:Clinicians should check patients' iron (particularly in menstruating women) and vitamin D status to correct any deficiency. Adequate selenium intake is vital in areas of iodine deficiency/excess, and in regions of low selenium intake a supplement of 50-100 μg/day of selenium may be appropriate. 10.1089/thy.2016.0635
Correlation Between Vitamin B12 Deficiency and Autoimmune Thyroid Diseases. Endocrine, metabolic & immune disorders drug targets BACKGROUND:Autoimmune thyroid diseases (AITD) are the most prevalent organ-specific autoimmune disorders. Vitamin B12 plays an important role in the proper functioning of the immune system. The aim of this study was therefore to investigate the correlation between vitamin B12 deficiency and AITD. MATERIALS AND METHODS:A total of 306 patients (aged 18-65 years, mean - 37.6 ± 11.3 years and comprising 87 males and 219 females) were studied retrospectively (observational study). Patients were divided into groups: with and without vitamin B12 deficiency, and with and without AITD. Differences between groups were evaluated by Fisher's exact test for qualitative variables and by Student's t-test for quantitative variables. Correlations for quantitative factors were determined by the Pearson correlation coefficient and for qualitative factors by Spearman correlation analysis. The sensitivity and specificity of vitamin B12 deficiency for AITD were calculated by ROC analysis. RESULTS:The vitamin B12 level was significantly lower in patients with AITD (and 200.70 + 108.84) compared to controls (393.41+150.78 p<0.0001). Patients with vitamin B12 deficiency were characterized by significantly higher mean values of anti-TPO (236.60+455.74) compared to controls (39.51+165.57 p<0.0001). Vitamin B12 levels were inversely correlated to anti-TPO levels (r=- 0.233, p<0.001). Roc analysis of vitamin B12 as a diagnostic test for AITD gave the area under curve as 0.881 (95% CI: 0.839-0.924), a sensitivity of - 0.947, a specificity of - 0.768, and a cutoff value of - 178.9. CONCLUSION:The vitamin B12 level correlates significantly to AITD. The concentration of vitamin B12 should therefore be determined in patients with autoimmune thyroiditis as a diagnostic test with high sensitivity and good specificity. 10.2174/1871530322666220627145635
Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis. Frontiers in endocrinology Background and aims:Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD. Methods:A meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597). Results:We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively. Conclusions:Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422). 10.3389/fendo.2023.1070592
Energetic homeostasis achieved through biophoton energy and accompanying medication treatment resulted in sustained levels of Thyroiditis-Hashimoto's, iron, vitamin D & vitamin B12. Metabolism open We present the case of a 37-year-old premenopausal woman, who presented with fatigue, weakness, pallor, and myalgias. She was on treatment for Hashimoto's Thyroiditis, iron deficiency anemia, deficiency of vitamin D and B12. Further diagnostic workup revealed her anemia was attributed to a long history of menorrhagia, deficiency of vitamin D and B12 which was attributed to Celiac disease. Her overall health improved with daily medication and by being around the biophoton generators, a device-generated biophoton field. Supplemental exposure to biophoton energy stabilized her blood component levels and improved the functional and energetic conditions of all her organs and systems. 10.1016/j.metop.2023.100248
Role of Dietary Supplements in Thyroid Diseases. Endocrine, metabolic & immune disorders drug targets BACKGROUND:Thyroid hormones play a vital role in regulating our body's metabolism. Two important thyroid hormones released from the thyroid gland are tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid-stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although normally, the hormonal diseases cannot be cured, but we can improve their signs and symptoms using suitable dietary supplements. OBJECTIVE:The aim of the study was to thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in Hashimoto's thyroiditis; hyperthyroidism, as seen in Graves' disease; sick euthyroidism and subclinical hypothyroidism. METHODS:Literature was searched using the search terms "dietary supplements+thyroid diseases" on Pubmed, Google Scholar, Scopus, Cochrane Library, and other search engines, and data were collected from 1967 to November, 2021, including research inputs from the authors. The literature was thoroughly searched, and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. CONCLUSION:After analyzing various studies on this topic, we arrived at the conclusion that although there are various claimed and observed health benefits of dietary supplements in the prevention and treatment of various thyroid disorders, still several studies have shown too many risks to be associated with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status. 10.2174/1871530322666220419125131
Metabolic Characteristics of Hashimoto's Thyroiditis Patients and the Role of Microelements and Diet in the Disease Management-An Overview. International journal of molecular sciences Hashimoto's thyroiditis (HT) is the most common autoimmune disease and the leading cause of hypothyroidism, in which damage to the thyroid gland occurs due to the infiltration of lymphocytes. It is characterized by increased levels of antibodies against thyroid peroxidase and thyroglobulin. In this review, we present the metabolic profile, the effectiveness of micronutrient supplementation and the impact of dietary management in patients with HT. For this current literature review, the databases PubMed, Cochrane, Medline and Embase were reviewed from the last ten years until March 2022. This article provides a comprehensive overview of recent randomized controlled trials, meta-analyses, and clinical trials. Many patients with HT, even in the euthyroid state, have excess body weight, metabolic disorders, and reduced quality of life. Due to frequent concomitant nutritional deficiencies, the role of vitamin D, iodine, selenium, magnesium, iron and vitamin B12 is currently debated. Several studies have underlined the benefits of vitamin D and selenium supplementation. There is still no specific diet recommended for patients with HT, but a protective effect of an anti-inflammatory diet rich in vitamins and minerals and low in animal foods has been suggested. There is insufficient evidence to support a gluten-free diet for all HT patients. Pharmacotherapy, along with appropriate nutrition and supplementation, are important elements of medical care for patients with HT. The abovementioned factors may decrease autoantibody levels, improve thyroid function, slow down the inflammatory process, maintain proper body weight, relieve symptoms, and prevent nutritional deficiencies and the development of metabolic disorders in patients with HT. 10.3390/ijms23126580
MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis. Endocrine connections Objective:Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods:Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results:After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion:Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis. 10.1530/EC-23-0477
Nutrition and thyroid disease. Current opinion in endocrinology, diabetes, and obesity PURPOSE OF REVIEW:The aim of this review was to determine, based on the most recent findings, the involvement of trace elements and vitamins critical for thyroid function and combating thyroid disease. RECENT FINDINGS:Nutritional guidance is pivotal to reducing the risk of thyroid disease and to managing it when it arises, this meaning the prescription of diets rich in such micronutrients as iodine, selenium, iron, zinc, and vitamins B12, D3, and A. Most of the above micronutrients are good antioxidants, building up an anti-inflammatory profile, reducing thyroid autoantibodies and body fat, and improving thyroid function. Diets are increasingly being prescribed, especially for those suffering from Hashimoto's thyroiditis. Notable among prescribed diets is the Mediterranean diet. Rich in critical elements, it benefits patients at the immune endocrine and biomolecular levels. SUMMARY:Importantly, it is likely that widespread adherence to the Mediterranean diet, together with a reduction of meat consumption and potential elimination of gluten and lactose may improve inflammation and have an impact on public health while possibly diminishing thyroiditis symptoms. It is hoped that this review can direct policymakers towards undertaking cost-effective interventions to minimize deficiency of essential minerals and vitamins and thus protect both general and thyroid health. 10.1097/MED.0000000000000831
The Effect of Gluten-Free Diet on Thyroid Autoimmunity in Drug-Naïve Women with Hashimoto's Thyroiditis: A Pilot Study. Krysiak Robert,Szkróbka Witold,Okopień Bogusław Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association BACKGROUND:Autoimmune thyroid disease is often accompanied by celiac disease. OBJECTIVE:The purpose of this study was to investigate whether a gluten-free diet affects thyroid autoimmunity, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in women with Hashimoto's thyroiditis and incidentally found positive anti-tissue transglutaminase antibodies. METHODS:The study included 34 women with autoimmune thyroiditis divided into two group. The patients belonging to the first one (group A, n=16) complied with the gluten-free diet for 6 months, while the remaining patients (group B, n=18) remained without any dietary treatment. Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured at the beginning of the study and 6 months later. Based on thyrotropin and free thyroid hormone levels, Jostel's thyrotropin index, the SPINA-GT index and the SPINA-GD index were calculated. RESULTS:All patients completed the study protocol. In group B, serum thyrotropin and free thyroid hormones levels, serum 25-hydroxyvitamin D levels as well as the calculated indices remained at the similar levels. The gluten-free diet reduced thyroid antibody titers, as well as slightly increased 25-hydroxyvitamin D levels and the SPINA-GT index. In group A, the impact on TPOAb and TgAb titers correlated with the changes in the SPINA-GT index, whereas the impact on TPOAb with the changes in 25-hydroxyvitamin D levels. CONCLUSIONS:The obtained results suggest that the gluten-free diet may bring clinical benefits to women with autoimmune thyroid disease. 10.1055/a-0653-7108
Stress Management in Women with Hashimoto's thyroiditis: A Randomized Controlled Trial. Journal of molecular biochemistry AIM:Stress has been implicated in the pathogenesis of Hashimoto's thyroiditis (HT), nevertheless evidence is scarce regarding the effect of stress management on individuals suffering from HT. The purpose of this study was to evaluate the impact of an 8-week stress management intervention on the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies as well as thyroid-stimulating hormone (TSH) levels of women with HT. Secondary endpoints included the effect on the patients' lifestyle, body mass index (BMI), depression, anxiety and stress. METHODS:This was a two-arm parallel group (stress management intervention vs. standard care groups) randomized controlled study. Adult women with Hashimoto's thyroiditis, completed questionnaires on stress, anxiety, depression and lifestyle, at the beginning of the programme and 8 weeks later. Laboratory thyroid function tests (anti-TPO, anti-TG antibodies and TSH) were also measured at baseline and at the end of the study. RESULTS:A total of 60 women with HT, aged 25-76 years, participated in the study (30 patients in each group). After eight weeks, patients in the intervention group demonstrated statistically significant beneficial decrements in the rate change of anti-TG titers and the levels of stress, depression and anxiety as well as better lifestyle scores, compared to the control group.
The importance of nutritional factors and dietary management of Hashimoto's thyroiditis. Ihnatowicz Paulina,Drywień Małgorzata,Wątor Paweł,Wojsiat Joanna Annals of agricultural and environmental medicine : AAEM Hashimoto (HT) is an autoimmune disease in which destruction of the thyroid occurs as a result of lymphocyte infiltration. It is caused by an increased level of titers of antibody against thyroid peroxidase (TPO) and thyroglobulin (TG). Because of that,in HT patients, changes are observed in the level and metabolism of thyroid hormones, which leads to unspecified physical and psychological symptoms. A high level of antibodies attacking thyroid antigens has been positively correlated with the symptoms. From the etiological point of view, the most important are genetic factors; however, environmental factors are necessary to provoke the immune system to attack until the process is over. Scientists indicate specified stress, toxification, microbiota dysbiosis and under- or over-nutrition, to name only a few. Dietotherapy of Hashimoto's is based on the proper nourishment of the body and regulation of the immune system by an anti-inflammatory diet. Observational and controlled trials have shown frequent nutrition deficiencies in HT patients. In literature, there is evidence for selenium, potassium, iodine, copper, magnesium, zinc, iron, vitamin A, C, D and B. The role of the proper level of protein intake, dietary fibre and unsaturated fatty acids, especially the n-3 family, has been indicated. HT patients should often eliminate lactose because of intolerance and interactions with levothyroxine and gluten because of possible interactions of gliadin with thyroid antigens. The article describes the nutrition factors of HT patients, and share nutrition recommendations for diet therapy. 10.26444/aaem/112331
Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto's Thyroiditis. Ruggeri Rosaria Maddalena,Giovinazzo Salvatore,Barbalace Maria Cristina,Cristani Mariateresa,Alibrandi Angela,Vicchio Teresa M,Giuffrida Giuseppe,Aguennouz Mohamed H,Malaguti Marco,Angeloni Cristina,Trimarchi Francesco,Hrelia Silvana,Campennì Alfredo,Cannavò Salvatore Thyroid : official journal of the American Thyroid Association There is a growing awareness that nutritional habits may influence risk of several inflammatory and immune-mediated disorders, including autoimmune diseases, through various mechanisms. The aim of the present study was to investigate dietary habits and their relationship with redox homeostasis in the setting of thyroid autoimmunity. Two hundred subjects (173 females and 27 males; median age, 37 years) were enrolled. None were under any pharmacological treatment. Exclusion criteria were any infectious/inflammatory/autoimmune comorbidity, kidney failure, diabetes, and cancer. In each subject, serum thyrotropin (TSH), free thyroxine, antithyroid antibodies, and circulating oxidative stress markers were measured. A questionnaire on dietary habits, evaluating the intake frequencies of food groups and adherence to the Mediterranean diet, was submitted to each participant. Among the 200 recruited subjects, 81 (71 females and 10 males) were diagnosed with euthyroid Hashimoto's thyroiditis (HT); the remaining 119 (102 females and 17 males) served as controls. In questionnaires, HT subjects reported higher intake frequencies of animal foods (meat,  = 0.0001; fish,  = 0.0001; dairy products,  = 0.004) compared with controls, who reported higher intake frequencies of plant foods (legumes,  = 0.001; fruits and vegetables,  = 0.030; nuts,  = 0.0005). The number of subjects who preferentially consumed poultry instead of red/processed meat was lower in HT subjects than in controls ( = 0.0141). In logistic regression analysis, meat consumption was associated with increased odds ratio of developing thyroid autoimmunity, while the Mediterranean diet traits were protective. In HT subjects, serum advanced glycation end products (markers of oxidative stress) were significantly higher ( = 0.0001) than in controls, while the activity of glutathione peroxidase and thioredoxin reductase, as well as total plasma antioxidant activity, were lower ( = 0.020,  = 0.023, and  = 0.002, respectively), indicating a condition of oxidative stress. Stepwise regression models demonstrated a significant dependence of oxidative stress parameters on consumption of animal foods, mainly meat. : The present study suggests a protective effect of low intake of animal foods toward thyroid autoimmunity and a positive influence of such nutritional patterns on redox balance and potentially on oxidative stress-related disorders. 10.1089/thy.2020.0299
Thyroid Autoimmunity: An Interplay of Factors. Merrill Stephen J,Minucci Sarah B Vitamins and hormones The literature on thyroid autoimmunity has identified many potential factors at play for the initiation and progression of autoimmune thyroid diseases. These factors include genetic susceptibility, environmental factors, some drugs, iodine and selenium, infection, molecular mimics, and immune system defects. The sheer number of feasible factors makes sorting out the necessary agents from the fellow travelers difficult. In addition, many of these factors have the capability to interact-further confusing the picture. Another difficulty in interpreting these data is that most proposed mechanisms are not able to accomplish the triggering event in which the tolerance to self-antigens is actually overcome. In addition, some findings may be describing the conditions present after a disease is diagnosed and may be consequences of the disease rather than a cause. Recent description of the role of adipokines, which include leptin, tumor necrosis factor-alpha, and interleukin-6, in contributing to the inflammatory environment of the thyroid, along with the presence of thyroid Toll-like receptors for pathogen-associated patterns have the potential to deliver that necessary adjuvant signal to break tolerance, seen as necessary in animal autoimmune models. An additional factor, vitamin D, due to its interaction both with white adipose tissue (WAT) and the immune system, has a complicated and somewhat controversial story with respect to thyroid autoimmunity. Conflicting results can result when not all factors are considered together. AIMS:To describe the many factors at play in thyroid autoimmunity and how they interact. CONCLUSION:Thyroid autoimmunity is the result of an interplay of factors, with adipokines produced by WAT and vitamin D providing immune modulating signals external to the thyroid, while thyrocyte innate responses to environmental conditions provide the necessary adjuvant signal. Shaping the response to be reactive to particular self-antigens and likelihood of a response are due to genetics and molecular mimics. 10.1016/bs.vh.2017.07.001
[SUBACUTE THYROIDITIS AND COVID-19 (REVIEW)]. Georgian medical news The COVID-19 pandemia has shown that there is not enough knowledge today to fully control it. Along with severe respiratory syndrome, attention has recently been paid to extrapulmonary lesions, including endocrinopathies. The aim of the study was to summarize the current literature data about the effects of the SARS-CoV-2 coronavirus on the thyroid gland. One of the most striking manifestations of viral aggression is de Quervain's subacute thyroiditis. The analysis of works from the most authoritative international abstract bibliographic databases was carried out using methods of analysis and processing of scientific resources. Based on the analysis, it was concluded that subacute thyroiditis can be both a clinical manifestation and a complication of COVID-19. The SARS-CoV-2 coronavirus can also trigger other thyroid diseases. The causes of subacute thyroiditis are considered to be the direct effect of the SARS-CoV-2 coronavirus on thyroid cells due to the use of ACE2 receptors, the subsequent inflammatory reaction and apoptosis, as well as central hypothalamus-pituitary mechanisms. The clinical variants of subacute thyroiditis in COVID-19 are diverse and have not been fully evaluated. In this regard, it can be concluded that the true incidence of subacute thyroiditis in COVID-19 is much greater, since it is masked by severe lesions of other organs.
Microorganisms associated to thyroid autoimmunity. Cuan-Baltazar Yunam,Soto-Vega Elena Autoimmunity reviews Autoimmune thyroid diseases are a group of diseases characterized by a dysfunction of the immune system concerning the thyroid gland, associated with hypothyroidism or hyperthyroidism. The thyroid gland autoimmunity has been recognized as multifactorial. It has been reported that microorganisms may play a role on the pathogenesis of Hashimoto's thyroiditis and Graves´ disease. These could explain the high incidence of the autoimmune thyroid diseases. Helicobacter Pylori (H. pylori) and Hepatitis C virus (HCV) are the microorganisms in which the association with autoimmune thyroid diseases is clearer. The pathophysiologic mechanisms are still not well defined. For H. pylori, molecular mimicry has been the most accepted mechanism. It has been proposed Hepatitis C virus as the trigger of the thyroid autoimmunity by exacerbating the production of thyroid auto-antibodies, while some mention that the real factor that triggers the thyroid autoimmunity is the treatment with Interferon alpha (IFN-alpha) by upregulating MHC class I and inducing ligation of CD40+ cells to thyrocytes. Other microorganisms such as Toxoplasma gondii, Human Immunodeficiency virus, Herpes virus and others have reported information about their association with thyroid autoimmune diseases There are no proposals on how these last microorganisms induce thyroid autoimmunity. There is still a lack of evidence on this topic. Further research must be done to determine the interaction of these microorganisms and the best way to manage these patients. 10.1016/j.autrev.2020.102614
COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms. Journal of medical virology Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms. 10.1002/jmv.29001
Thyroid Diseases and Intestinal Microbiome. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases. 10.1055/a-2190-3847
Impact of Vitamin D on Immunopathology of Hashimoto's Thyroiditis: From Theory to Practice. Nutrients Hashimoto's thyroiditis (HT) is a common autoimmune disease affecting the thyroid gland, characterized by lymphocytic infiltration, damage to thyroid cells, and hypothyroidism, and often requires lifetime treatment with levothyroxine. The disease has a complex etiology, with genetic and environmental factors contributing to its development. Vitamin D deficiency has been linked to a higher prevalence of thyroid autoimmunity in certain populations, including children, adolescents, and obese individuals. Moreover, vitamin D supplementation has shown promise in reducing antithyroid antibody levels, improving thyroid function, and improving other markers of autoimmunity, such as cytokines, e.g., IP10, TNF-α, and IL-10, and the ratio of T-cell subsets, such as Th17 and Tr1. Studies suggest that by impacting various immunological mechanisms, vitamin D may help control autoimmunity and improve thyroid function and, potentially, clinical outcomes of HT patients. The article discusses the potential impact of vitamin D on various immune pathways in HT. Overall, current evidence supports the potential role of vitamin D in the prevention and management of HT, although further studies are needed to fully understand its mechanisms of action and potential therapeutic benefits. 10.3390/nu15143174
Alterations and Mechanism of Gut Microbiota in Graves' Disease and Hashimoto's Thyroiditis. Polish journal of microbiology To explore the role of gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and _2 and lower levels of and . Further analysis of KEGG found that the "ABC transporter" metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that , , and could be used as potential markers to distinguish GD and HT from the healthy population and that "ABC transporter" metabolic pathway may be involved in the pathogenesis of GD and HT. 10.33073/pjm-2022-016
Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease. Zhao Rui,Zhang Wei,Ma Chenghong,Zhao Yaping,Xiong Rong,Wang Hanmin,Chen Weiwen,Zheng Song Guo Frontiers in immunology Vitamin D is one of the most important nutrients required by the human body. It is a steroid hormone that plays an important role in regulating calcium and phosphorus metabolism, and bone health. Epidemiological studies have revealed a close correlation between vitamin D and many common chronic diseases. Additionally, vitamin D has recently been shown to act as an immunomodulatory hormone, and, accordingly, vitamin D deficiency was uncovered as a risk factor for autoimmune thyroid diseases, although the underlying mechanisms are still unknown. It is therefore necessary to disclose the role and mechanism of action of vitamin D in the occurrence and development of autoimmune thyroid diseases. This knowledge will help design intervention and early treatment strategies for patients with autoimmune thyroid diseases who present with low levels of vitamin D. 10.3389/fimmu.2021.574967
Interleukin-1 beta inhibits rat thyroid cell function in vivo and in vitro by an NO-independent mechanism and induces hypothyroidism and accelerated thyroiditis in diabetes-prone BB rats. Reimers J I,Rasmussen A K,Karlsen A E,Bjerre U,Liang H,Morin O,Andersen H U,Mandrup-Poulsen T,Burger A G,Feldt-Rasmussen U,Nerup J The Journal of endocrinology Interleukin-1 beta has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1 beta dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1 beta. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1 beta-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1 beta-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor NG-monomethylarginine did not ameliorate the effect of interleukin-1 beta on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1 beta for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1 beta-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1 beta in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells. 10.1677/joe.0.1510147
TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells. Li Hong,Zhang Xia,Gao Long,Min Jie,Zhang Yali,Zhang Ren,Yang Yucheng Discovery medicine Tumor necrosis factor alpha (TNF-α) regulates the expression of proinflammatory cytokines and apoptosis in thyroids. miR-155-5p is upregulated in circulating microvesicles in patients with autoimmune thyroiditis. However, the function and molecular mechanisms of TNF-α and miR-155-5p in the initiation and progression of subacute thyroiditis are largely unknown. Herein, we determined serum TNF-α levels in subacute thyroiditis patients and normal healthy controls by ELISA assay. Proliferation and apoptosis of rat thyroid follicle FRTL-5 cells were determined by MTT, TUNEL, and annexin V staining assays. Protein levels and phosphorylation status were assessed by immunoblotting. miR-155-5p expression was determined by the real-time quantitative PCR. Serum TNF-α was significantly upregulated in patients with subacute thyroiditis compared to that in normal healthy controls. In rat thyroid follicle FRTL-5 cells, TNF-α treatment led to a reduction of cell proliferation and an induction of apoptosis. It also increased IL-6 expression and phosphorylation of JAK2 and STAT3. Importantly, we demonstrated that serum miR-155-5p was upregulated in subacute thyroiditis patients and TNF-α stimulated the expression of miR-155-5p in FRTL-5 cells. We found that miR-155-5p inhibited the proliferation and induced apoptosis of FRTL-5 cells and increased the expression of IL-6 in FRTL-5 cells. Our results demonstrated that serum TNF-α and miR-155-5p were upregulated in patients with subacute thyroiditis, and TNF-α inhibited proliferation and induced apoptosis of rat thyroid follicle FRTL-5 cells via modulating the IL-6-JAK2/STAT3 pathway and miR-155-5p signaling. Our findings suggest that miR-155-5p might be a novel biomarker of subacute thyroiditis.
Is lymphocytic thyroiditis a unique type or merely a type of Hashimoto's thyroiditis? Todorovic J,Nesovic Ostojic J,Opric D,Dundjerovic D,Bozic V,Markovic L Minerva medica AIM:Objective of the study was to clarify the role of apoptosis in the pathogenesis of lymphocytic thyroiditis (LT) and the existence of difference between Hashimoto's thyroiditis (HT) and LT. METHODS:We evaluated levels of antithyroglobulin and antithyroperoxidase antibodies, the apoptosis by in situ Cell Death Detection-TUNEL and the expression of Bcl2 and Bax by immunohistochemistry in thyroid tissues from 16 patient with HT, 10 with LT and 10 with euthyroid goiter-EG (control group). RESULTS:It was found that apoptosis of thyrocytes in HT (mean 3.05%, SD 1.29%) and LT (mean 2.70%, SD 1.17%) was statistically significantly higher than EG (mean 0.56%, SD 0.23%), but the difference in the percentage of thyrocytes between HT and LT was not statistically significant. In HT the percentage of apoptotic infiltrating lymphocytes (mean 0.59%, SD 0.23%) was smaller than in EG (mean 2.26%, SD 1.42%), but it showed no significant difference in comparison to LT. The expression of Bax in infiltrating lymphocytes in HT (mean 0.72%, SD 0.34%) was statistically significantly higher than LT (mean 0.11%, SD 0.06%). The level of thyroglobulin was lower in HT compared to LT (P<0.01) and compared to EG (P<0.01). The level of antithyroglobulin/antithyroperoxidase antibodies was higher in HT compared to LT (P<0.01) and compared to EG (P<0.01). There was no statistically significant difference in the level of thyroglobulin and level of antibodies between LT and EG. CONCLUSION:These results suppose that apoptosis represents one of significant mechanisms in the pathogenesis of both HT and LT and that LT probably differs from HT.
Subacute thyroiditis following COVID-19 vaccination: Case presentation. Antiviral therapy Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19. The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine. Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal. Data collected during the disease are integral to the medical record. Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition. 10.1177/13596535231208831
Cytological, histopathological and immunological aspects of autoimmune thyroiditis: a review. Buzdugă Cătălin Mihai,Costea Claudia Florida,Dumitrescu Gabriela FlorenŢa,Turliuc Mihaela Dana,Bogdănici Camelia Margareta,Cucu Andrei,Dumitrescu Nicoleta,Indrei Lucia,Şapte Elena,Ciobanu Apostol Delia Gabriela Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie Autoimmune thyroiditis (AT) is a disease that may be associated with many other autoimmune endocrine and non-endocrine disorders. This disease is mediated by both humoral and cellular mechanisms and it is the result of combined effects of human leukocyte antigen (HLA) class II genes and non-HLA genes polymorphisms. The clinical course of AT is variable and may be characterized by spontaneous remission and by irreversible thyroid insufficiency as the consequence of atrophic and fibrous transformation of the thyroid gland in other cases. In this paper, the AT's etiology and immunological mechanism along with its cytological and histopathological features are reviewed in order to increase our understanding about the mechanism involved in pathogenesis of this disease and to open new directions of investigations that will be useful in a better clinical practice.
Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment. Polish archives of internal medicine Hashimoto thyroiditis (HT) is a common autoimmune disorder, affecting women 7-10 times more often than men, that develops because of genetic susceptibility, Xchromosome inactivation patterns modulated by environmental factors as well as microbiome composition, and leads to an imbalance in self‑tolerance mechanisms. The consequential thyroid infiltration by lymphocytes, potentiated by antibody‑mediated autoimmune response through the antibodies against thyroid peroxidase (TPOAbs), leads to a destruction of thyrocytes. The presence of TPOAbs is associated with a 2 to 4‑fold increase in the risk of recurrent miscarriages and preterm birth in pregnant women. The clinical presentation of HT includes: (A) thyrotoxicosis, when stored thyroid hormones are released to circulation from destroyed thyroid follicles; (B) euthyroidism, when preserved thyroid tissue compensates for destroyed thyrocytes; and (C) hypothyroidism, when thyroid hormone production by the affected thyroid gland is insufficient. The management of Hashitoxicosis is based on symptoms control usually with β‑blockers, euthyroidism requires periodical thyroid stimulating hormone measurements to assess for progression to hypothyroidism, and hypothyroidism is treated with thyroid hormone replacement therapy. The dose of levothyroxine (LT4) used for treatment is based on the degree of preserved thyroid functionality and lean body mass, and usually ranges from 1.4 to 1.8 mcg/kg/day. There is insufficient evidence to recommend for or against therapy with triiodothyronine (T3), apart from in pregnancy when only levothyroxine is indicated, as T3 does not sufficiently cross fetal blood‑brain barrier. HT is associated with 1.6 times higher risk of papillary thyroid cancer and 60 times higher risk of thyroid lymphoma than in general the population. 10.20452/pamw.16222
An update on the pathogenesis of Hashimoto's thyroiditis. Weetman A P Journal of endocrinological investigation It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto's thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT. 10.1007/s40618-020-01477-1