Treatment Of Hashimoto's Thyroiditis Research Articles

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto disease? Findings from studies on newly-diagnosed patients.

Epstein‑Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto thyroiditis (HT). This study examined the association between EBV reactivation and intracellular Toll‑like receptor (TLR) expression in newly‑diagnosed, untreated HT patients. Its aim was to determine whether EBV reactivation and expression of specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT. The study involved a cohort was 54 newly‑diagnosed, untreated patients with HT and 20 healthy volunteers (HVs) matched for age and sex. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. The levels of specific anti‑EBV antibodies (eg, viral capsid A [VCA] immunoglobulin [Ig] M, VCA IgG, Epstein‑Barr nuclear antigen 1 [EBNA‑1] IgM, EBNA‑1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using enzyme‑linked immunosorbent assay. Notably, our HT patients were not euthyroid, as they exhibited significantly lower thyroid‑stimulating hormone levels and elevated free triiodothyronine and free thyroxine levels in comparison with the HVs. The study showed a significant increase in EBV reactivation among the HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, as compared with none of the HVs. The HT patients with reactivated EBV showed significantly higher intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes (vs 0.69% in the HVs), suggesting a potential synergistic effect. In addition, sTLR levels increased in the HT patients with reactivated EBV, suggesting a possible role of these receptors in potentiating autoimmune responses. These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to development of new therapeutic approaches to mitigate the impact of these factors on the disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

Clinical comparative efficacy and therapeutic strategies for the Hashimoto's thyroiditis: A systematic review and network meta-analysis

Ethnopharmacological relevanceVitamin D (VD), selenium preparations (Se), and thyroid hormone replacement therapy are commonly used to treat Hashimoto thyroiditis (HT). Increasing evidence suggests that traditional Chinese medicine (TCM) is an effective therapeutic strategy in the treatment of HT. Aim of the studyThis study aimed to investigate the efficacy and safety of commonly-used drugs for HT. Materials and methodsA literature search was performed using PubMed, Web of Science, Cochrane Library, EMBASE, Chinese China National Knowledge Infrastructure (CNKI), Clinical Trial Registry (Chi CTR), China Science and Technology Journal Database (the VIP), Wanfang Database, and China Chinese Biomedical Database (CBM) from January 1, 2003, to December 31, 2022. The outcomes included TPOAb, TgAb, TSH, FT3, FT4, and adverse events. Our study was registered in PROSPERO (CRD42023449705). ResultsSixty trials and 4719 participants were included, comparing 16 treatments: VD, Se, LT-4, Se + LT-4, HM, placebo + LT-4, HM + LT-4, Se + myolnositol, Se + VD, HM + Se, mannan peptide, LT-4+prednisone, Methimazole, Methimazole + HM, Tapazole + Propranolol, and placebo. We found that Chinese herbal medicine has significant effect vs. LT-4 [MD 0.10, 95 % confidence interval 0.02 to 0.50]) and LT-4+placebo [MD 0.10, 95 % confidence interval 0.01 to 0.77]) in reducing TPOAb. Although receiving LT-4+prednisone was not statistically significant, the treatment ranking showed that this combination therapy had the highest probability of reducing TPOAb levels (72.8 %). In addition, the effect of Se plus LT-4 was not statistically significant; however, the treatment ranking showed that this combination therapy had the highest probability (78.6 %) of reducing TgAb levels, followed by HM (64.0 %). Reports on side effects have mainly focused on the digestive and cardiovascular systems. ConclusionOur analyses showed that HM alone or in combination with other treatments for patients with HT can improve the side effects of other drugs, enhance efficacy, and maybe the most effective option for treating HT. However, there still need further verified using high-quality evidence.

Role of Micronutrient Supplementation in the Management of Hashimoto's Thyroiditis: A Review of Current Evidence and Potential Mechanisms of Action

Introduction and objective: Hashimoto's thyroiditis (HT), the most prevalent autoimmune disorder and a primary cause of hypothyroidism globally, leads to thyroid gland damage through lymphocyte infiltration. Pharmacological treatment of HT involves the use of levothyroxine, which in most cases must be taken for life. However, supplementation with micronutrients is often overlooked. Several studies have examined the impact of substances such as selenium, zinc, vitamin B12, and vitamin D on the course of Hashimoto's disease. Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed. Abbreviated description of the state of knowledge: Supplementation with selenium, zinc, vitamin D, and B12 shows potential benefits for patients with Hashimoto's disease. Summary: Regular monitoring and tailored supplementation of selenium, zinc, vitamin D, and vitamin B12 can enhance overall health and disease management. Therefore, it is worth considering the supplementation of these micronutrients in the daily routine of patients with Hashimoto's thyroiditis. However, it should be noted that these supplements do not constitute a treatment for Hashimoto's disease and their effect cannot replace the intake of levothyroxine.

Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

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.

Gene network analysis of vitamin D for Hashimoto's thyroiditis

Objective: It has been well known that Vitamin D plays an ameliorative effect on the treatment of Hashimoto's thyroiditis (HT), but the underlying mechanism is largely unknown. This study was conducted to analyze the gene network mechanism in the treatment of HT by Vitamin D. Methods: The related genes were retrieved from the GeneCards database using the keywords ‘Hashimoto's thyroiditis’ and ‘Vitamin D’, and the retrieved genes were used to make a Venn intersection map. The obtained genes were used to construct a protein-protein interaction (PPI) network with the STRING database. These key genes were enriched and analyzed by gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: 602 genes were found to be intersected between HT and Vitamin D. The GO enrichment analysis of HT and Vitamin D is mainly involved in the regulation of T cell activation, leukocyte proliferation, mononuclear cell proliferation, regulation of cell-cell adhesion, lymphocyte proliferation, etc. The results from KEGG pathway analysis were mainly related to Cytokine-cytokine receptor interaction, AGE-RAGE signaling pathway in diabetic complications, Inflammatory bowel disease, Lipid and atherosclerosis, Rheumatoid arthritis, JAK-STAT signaling pathway, EGFR tyrosine kinase inhibitor resistance, human T-cell leukemia virus 1 infection, type I diabetes mellitus, signaling pathway, etc. The top 10 genes of the protein-protein interaction (PPI) network were AGER: S100B, AGO2: DICER1, AGRN: MUSK, AGT: REN, AKT1: NOS3, AKT1: MTOR, ANGPT1: TEK, ANGPT2: TEK, AR: FOXA1, AR: NCOA4. Conclusions: From the analytic results, vitamin D has a regulatory effect on HT.

Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: A systematic review and meta-analysis.

Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT. A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs). After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment. Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.

Treatment of Hashimoto Thyroiditis from Liver Based on "Kido Tatsuki"

Treatment of Hashimoto Thyroiditis from Liver Based on "Kido Tatsuki"

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). The mean age of the enrolled participants was 44.35years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [-16.42 (-22.18, -10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67μg, Log2-transformed). Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

Reset your Immune System: Acceptability and Preliminary Effects of a CMT-Based Intervention in Patients with Hashimoto Thyroiditis

Patients with Hashimoto thyroiditis (HT) experience mental health complaints due to the immune system dysregulation. Preliminary evidence suggests that psychological interventions could improve patients’ quality of life. Compassionate mind training (CMT) is part of compassion-focused therapy (CFT) and can be used to help individuals address physical and mental health difficulties. The present study sought to assess the acceptability and preliminary efficacy of Reset Your Immune System, a 6-week CMT-based online intervention, in patients with HT. Nine women were randomly selected from a wider sample that undertook the online intervention. Upon completion, they were interviewed with nine standard open-ended questions. Additionally, pre- and post-intervention questionnaires were filled out. Qualitative analysis indicated that participants observed improvements in symptoms, sleep quality, self-awareness, stress-management, and self-regulation skills. Participants did experience some difficulties in undertaking compassion-related exercises. Quantitative analyses showed that negative affect, social/role limitations, and HT symptoms indicated a reliable change from pre- to post intervention. Overall, Reset Your Immune System showed beneficial effects on patients with HT, suggesting that including psychological care as part of the standard treatment of HT might have added value. It is important to assess long-term effects in a larger sample through a randomized control trial.

Report on Steroid- Responsive Encephalopathy in a Case of Hashimoto’s Thyroiditis

Introduction: Thyroiditis caused by Hashimoto's common, Thyroid gland enlargement that is painless and diffuse that affects mostly women in their forties and fifties. While most patients are euthyroid, hypothyroidism may grow. In addition, several patients have thyroid antigen-specific cell-mediated immunity, which can be demonstrated using a variety of strategies. The annual number of cases per 10,000 people prevalence of at least 2% among women. Thyroiditis causes the thyroid gland to become extinct capacity to keep iodine in a safe place, generate together with secrete circulating iodoproteins in the blood, and produce inefficient hormone. As a result, the thyroid gland is overstimulated, and the patient has a high rate of Iodine in the thyroid turnover.&#x0D; Clinical Finding: enlargement of thyroid gland. Difficulty in swallowingand breathing, unexplained weight gain,constipation, slow heart beat, fatigue, swelling in extremities, dryness.&#x0D; Medical History: In 2010 she was suffering from same problems. Hashimoto thyroiditis cured for medical intervention in Nagpur medical college, after that treatment of Hashimoto thyroiditis she took the treatment in A.V.B. R. Hospitalfor management of Hashimoto thyroiditis. Now she is admitted in peadiatrics ward for further management of Hashimoto thyroiditis.&#x0D; The Diagnosis and Therapeutic Intervention: After physical examination and investigation, this case was diagnosed as Hashimoto thyroiditis. Thyroid hormone replacement therapy was used to treat the condition. This normally entails taking levothyroxine.&#x0D; Leoxyl Check: After six to eight weeks of treatment, the TSH level should be normal with dose 12.5-25 mcg. Absorption of levothyroxin may be affected by some drugs, supplements, and diets taken 4 hours. Triiodothyronine 5 to 10 mcg received in twice in day.&#x0D; Nursing Perspectives: Assessement of anterior or posterior location of the thyroid IV Fluid was provided. Check blood pressure and vital signs per hourly. Monitor the Pulse oximetry, ABG, and respiratory rate, and pattern are all factors to consider.&#x0D; Conclusion: Comprehensive systemic review of autoimmune disease, our best estimate of incidence rates for hypothyroidism in female and male treatment and management improves the outcomes of Hashimoto thyroiditis.

What is the impact of thyroidectomy on autoimmune features associated with Hashimoto's thyroiditis?-Institutional experience.

Hashimoto's thyroiditis (HT) is one of the commonest endocrine disorders, globally. Often, HT presents a protean range of associated autoimmune features (AAI) such as vitiligo, rheumatoid arthritis, pernicious anemia, skin allergy/atopy, thrombocytopenia, Addison's disease, type 1 diabetes, celiac disease, eosinophilia, etc., The usual treatment of HT is symptomatic with no curative option. In this context, we report our experience on the impact of surgical thyroidectomy on remission of AAI in HT. To report our experience on the impact of surgical thyroidectomy on remission of AAI in patients with HT. This is a retrospective study conducted in the Endocrine Surgery department of a tertiary care hospital. A total of 61 patients with HT and various AAI combinations were included in this study. All the clinicoinvestigative and operative data were systematically analyzed. The most frequent indication for surgery was nodular goiter followed by associated malignancy, persistent goiter, and painful thyroiditis. Others were cosmetic/pressure symptoms and not AAI per se. The mean follow-up after surgery was 55.6 ± 11.8 months. The gender ratio was 5.8:1 in favor of women and the mean age was 41.5 ± 5.4 years. The mean preoperative and postoperative serum anti-thyroperoxidase antibody (Anti-TPO Ab) levels were 339 ± 98.2 and 58.75 ± 25 IU/L at the last follow-up visit. A total of 60% AAI manifestations had resolution or significant alleviation. The major improvements in AAI were skin allergy, eosinophilia, rheumatoid arthritis, vitiligo, thrombocytopenia, celiac disease symptomatic episodes; but, type 1 diabetes and Addison's disease showed static response. Surgical total thyroidectomy and anti-TPO Ab-related autoimmunity appear to play a beneficial role and definitive role in the remission of AAI in HT.

Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events

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, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA gene sequencing. Findings: We found that metformin indeed has a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly inhibits the formation of Th17 cells and M1 macrophages in vivo. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue showed that the therapeutic effect of metformin on HT is mainly achieved by regulating immune disorders. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differ significantly from that of the normal mice and also are altered by metformin treatment. Interpretation: This experiments provide a preliminary theoretical basis for the clinical application of metformin in the treatment of HT. Funding Statement: The present work was supported by grants from the National Natural Science Foundation of China (No.81873636 and No.81900710), Shanghai Natural Science Foundation (No.18ZR1433800). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All patients and healthy controls have signed informed consent. The study was approved by the ethical committees of Zhoupu Hospital and performed in accordance with relevant guidelines and regulations. All animal experiment procedures were approved by the Animal Ethics Committee of Fudan University.

Acupuncture for Hashimoto thyroiditis: study protocol for a randomized controlled trial

BackgroundThe incidence rate of Hashimoto thyroiditis (HT) has gradually increased in recent years. There has been no specific etiological treatment for HT. Even though with normal level of thyroid hormone, the patients may still suffer from various clinical symptoms, such as anterior neck discomfort, fatigue, and mood swings, which seriously impair their quality of life. Acupuncture has long been used in the treatment of thyroid diseases, but there has been no related standardized clinical study as of today. This study aims to assess the feasibility, efficacy, and safety of acupuncture for HT.MethodsThis is a randomized, black-controlled assessor-blinded pilot trial. A total of 60 patients will be recruited and divided into the experimental group (n = 30) or the control group (n = 30). The experimental group will undergo acupuncture therapy (penetration needling of Hand-Yangming meridian, PNHM) for 16 weeks, followed by a 16-week follow-up period, and the control group will first go through an observation period for 16 weeks, followed by a 16-week compensation PNHM therapy. The primary outcome will be the change of the concentrations of anti-thyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), and thyroid hormone, including total thyroxine (FT4), free thyroxine (FT3), and thyroid-stimulating hormone (TSH). The secondary outcome measurements include the thyroid-related quality of life questionnaire short-form (ThyPRO-39), The Mos 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HAD). Data collection will be performed before the start of the study (the baseline assessment) and at weeks 8, 16, 24, and 32.DiscussionThe study is designed to assess the feasibility and effectiveness of PNHM in reducing the thyroid antibody level and improving the quality of life of HT patients with hypothyroidism or subclinical hypothyroidism. Results of this trial will assist further analyses on whether the acupuncture treatment can alleviate symptoms for patients with HT.Trial registrationAcupuncture-Moxibustion Clinical Trial Registry AMCTR-IOR-19000308 (ChiCTR1900026830). Registered on 23 October 2019.

Effect of large dosage of Prunella on Hashimoto's thyroiditis

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)

Systematic review and trail sequential analysis of preparation of Xiakucao for Hashimoto's thyroiditis

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.

Role of Nampt overexpression in a rat model of Hashimoto's thyroiditis and its mechanism of action.

The present study was designed to investigate the role of nicotinamide phosphoribosyltransferase (Nampt) overexpression in a rat model of Hashimoto's thyroiditis (HT) and its mechanism of action. A rat model of HT was constructed, and the HT rats were injected with an adenoviral expression vector carrying the Nampt gene. The expression of Nampt and Toll-like receptor 4 (TLR4) in thyroid tissues was examined using immunohistochemistry (IHC), RT-qPCR and western blot analyses. Serum anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured using chemiluminescence method. Hematoxylin and eosin (H&E) and IHC staining of the rat thyroid tissues showed destroyed thyroid follicles and monocyte infiltration, as well as increased Nampt expression in the thyroid tissues of rats with HT. Furthermore, it was found that Nampt overexpression led to increased severity of inflammatory infiltration in thyroid tissues and increased levels of TPOAb in the serum of HT rats; however, the serum TGAb level was not affected by Nampt overexpression. In addition, Nampt overexpression promoted TLR4 expression in HT rats. In conclusion, it was demonstrated that Nampt was strongly expressed in the capillary region of HT rats thyroid tissues. The Nampt mRNA level was increased but the Nampt protein level was decreased in the thyroid tissues of rats with HT. Nampt overexpression has a promotive effect on HT progression, and this effect was related to TLR4. This study suggests that inhibition of Nampt activity may be valuable in the treatment of HT.

Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease.

Polymorphic variants of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and forkhead box protein P3 (FOXP3) genes are implicated in dysregulated immune homeostasis and autoimmune disorders. We analyzed the association between CTLA-4 rs231775 and FOXP3 rs3761548, rs3761549 polymorphisms and predisposition to autoimmune thyroid disease (AITD), inclusive of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in South-Indian population. A total of 355 AITD subjects (comprising 275 HT and 80 GD) and 285 randomly selected age- and sex-matched control subjects were genotyped for the aforementioned polymorphisms by PCR-RFLP method. The rs231775 "G" allele was preponderant in HT and GD subjects when compared with controls and exerted a dominant influence on the susceptibility to HT (p = 0.009) and GD (p = 0.02), respectively. There was no allelic association of rs3761548 and rs3761549 polymorphisms with AITD susceptibility, albeit a significant difference in genotype distribution with respect to rs3761549. Haplotype analysis revealed an increased frequency of rs3761548 "C"-rs3761549 "T" in HT and GD subjects, thereby associating it with disease predisposition (p = 0.03). Epistatic interaction analysis by multifactor dimensionality reduction approach revealed redundancy between CTLA-4 and FOXP3 genes in influencing the susceptibility to AITD. The genetic variation in CTLA-4 gene with reference to rs231775 polymorphism contributes to an increased predisposition to HT and GD. Also, in conjunction with FOXP3 gene variants it seems to influence the susceptibility to HT and GD respectively. The significance of these findings in combination with antithyroid antibody screening could plausibly contribute towards meticulous case-finding for effective treatment of HT and GD.

Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis.

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. 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. 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.

Pentoxifylline Explores New Horizons in Treatment of Hashimoto Thyroiditis

Hashimoto Thyroiditis is an autoimmune disease and the most common cause of hypothyroidism in developed countries. As the disease initiates unusual thyroidal antigens are exposed to the immune system. The immune system sensitizes to those antigens and creates a cell mediated autoimmune response against thyroid gland. Inflammatory cells infiltrate within thyroid follicles and destruct the follicles by inflicting oxidative stress and inducing apoptosis. The inflammatory process also reduces sensitivity of thyrocytes to Thyroid Stimulating Hormone (TSH). As the disease progresses and the follicles degrade, fibrotic tissue replaces the follicles until the whole gland becomes fibrotic. Pentoxiflline could inhibit autoimmune destruction of thyrocytes, suppress cell mediated immune response against thyroid, decrease oxidative damage to thyrocytes, increase sensitivity of thyrocytes to TSH and hinder fibrotic degeneration of thyroid. Thereby PTX could cure HT and alleviate symptoms of hypothyroidism.

The study of the coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma

Hashimoto's thyroiditis (HT) is the most common type of autoimmune thyroid disease, and the incidence is rising in recent years. The aim of this study was to evaluate the pathological characteristics, treatment and prognosis of HT with papillary thyroid carcinoma (PTC). From July 2004 to December 2011, 8,524 patients underwent thyroid surgery in our hospital and 1,735 patients were diagnosed with PTC. The data from these patients were statistically analyzed using SAS software. There were 839 patients with a final diagnosis of HT in this study. A greater incidence of PTC was found in those with HT (29.4 %) than those without HT (19.4 %; p < 0.05). Male HT patients had a significantly higher rate of PTC (27/61, 44.3 %) when compared to female patients (220/778, 28.3 %; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger (43.1 vs. 46.6, p < 0.01) and had smaller nodules (1.10 vs. 1.34 cm, p < 0.05), less external invasion (0.4 vs. 2.5 %, p < 0.05), less lymph node metastasis in lateral neck area (17.2 vs. 26.9 %, p < 0.05) and less advanced TNM stages than PTC patients without HT. Hashimoto's thyroiditis is associated with a significantly higher risk of PTC, and the incidence of PTC is much higher in male HT patients. More attention should be paid to HT patients, especially male HT patients, for signs of PTC. Based on the less aggressive pathological features in HT-PTC group, we should not blindly expand the indication and extent of surgery.