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Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may release free thyroid hormones into the bloodstream, causing hyperthyroid symptoms. With further destruction of thyroid cells, patients develop euthyroidism and eventually chronic hypothyroidism. The diagnosis of AIT is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound, and histological features. The main goal of treatment is correcting hormonal disorders and achieving euthyroidism. Treatment of AIT involves replacing thyroid hormone deficiency with the use of synthetic hormones. Prophylactic levothyroxine (L-T4) treatment of euthyroid patients with AIT may reduce both serological and cellular markers of autoimmunisation. Attention should be paid to the starting dose of L-T4, potential drug interactions, and drug formulation. A follow-up should be planned to determine the optimal dose. The authors highlighted that a healthy lifestyle and supplementing selected vitamins and microelements appropriately are essential. In selected clinical conditions, thyroidectomy should be considered. There are also alternative therapeutic strategies, such as herbal medicine and acupuncture, but their effectiveness has yet to be conclusively confirmed in research studies. Monitoring the thyroid gland enlargement and the possibility of developing nodular goitre is integral to patient care over AIT patients. In conclusion, treating AIT is complex, involving thyroid hormone replacement therapy, taking care of a healthy diet and lifestyle, and proper supplementation. It requires an individual approach. Regular follow-up is necessary to control the disease and minimise its effects.

This review on the 100th anniversary of the American Thyroid Association summarizes the remarkable progress attained during the past century regarding the pathogenesis and treatment of thyroid autoimmune diseases. Indeed, the general concept of autoimmune diseases in humans was established 70 years ago by thyroid investigators. Graves' disease is a paradigm for the rare occurrence of how autoimmunity can cause disease by stimulating rather than destroying an organ system. Therapeutic advances in the mid 20th century involving administration of thyroid hormones, thionamide drugs, and radioiodine have been hugely beneficial for human health. However, these approaches can only treat, but not cure, thyroid autoimmunity. Investigation of these diseases is facilitated by the identification of a limited number of specific autoantigens, whose molecular cloning has provided much information on their structure. This knowledge has led to highly sensitive and specific diagnostic tests, provided insight into novel aspects regarding the pathogenesis of thyroid autoimmunity, and has opened avenues for the development of new therapeutic agents. Immunotherapy for a cure as opposed to therapy of Graves' disease and Hashimoto's thyroiditis remains the holy grail for the 21st century.

Previously, we identified a new immunoregulatory factor, the production of which provides rats with resistance to certain experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). RegRF inhibits the expansion of CD4 T lymphocytes by killing activated cells. CD4 T cells are essential for antibody production against a majority of antigens and for the generation of cytotoxic T cells; therefore, regRF is an attractive therapeutic biotarget for T-cell and antibody-mediated autoimmune diseases. RegRF is anti-idiotypic antibodies that have a shared paratope in addition to an individual paratope. Epitopes specific to the shared regRF paratope (regRF epitopes) can be obtained on conformers of IgG Fc fragments. Immunization with Fc fragments carrying regRF epitopes reduces rat collagen-induced arthritis and diminishes experimental autoimmune encephalomyelitis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune thyroiditis (EAT). Four weeks after EAT induction, rats were immunized with IgG Fc fragments exhibiting regRF epitopes. Histology studies of the thyroid were performed 4 weeks later. Thyroid function and other parameters were also evaluated. Treatment of rats with Fc fragments bearing regRF epitopes decreased the number of rats affected by EAT, significantly decreased the extent of thyroid damage, prevented thyroid metaplasia, and restored normal thyroid hormone production. Therefore, RegRF is a promising biotarget in autoimmune thyroiditis, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for that condition., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Results of modern research show a relationship between emotional stress and the occurrence of autoimmune diseases as a comorbidity. The authors use EMDR therapy (Eye Movement Desensitization and Reprocessing) to treat trauma disorders. They wondered whether and to what extent this treatment also affects autoimmune processes., Method: Parallel to the trauma-focused psychotherapy with EMDR, the thyroid hormone substitution dose was documented in patients with active Hashimoto's autoimmune thyroiditis requiring substitution. Hashimoto's autoimmune thyroiditis had already been diagnosed by a specialist and drug treatment had been initiated before starting outpatient psychotherapy., Results and Conclusion: So far in five cases a decrease in autoimmune activity and a stability of the results in the follow-up between six months and one year could be observed. It is now necessary to examine whether these results can be confirmed in a larger number of patients and a diversity of therapists and whether these observations can be transferred to other somatic comorbidities., (© 2022. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This study aimed to investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on experimental autoimmune thyroiditis (EAT) and the underlying mechanisms by utilizing a porcine thyroglobulin-induced EAT rat model. The rats received four tail vein injections of vehicle or hUCMSCs at an interval of 7 days and were sacrificed on day 28 after the first injection. Hematoxylin and eosin staining and enzyme-linked immunosorbent assays (ELISAs) were used to assess the therapeutic effects of hUCMSCs on EAT. Splenic lymphocytes were isolated from rats, and the proportions of CD4 + T cell subsets were analyzed by flow cytometry. Splenic CD4 + T cells from EAT rats were cocultured with hUCMSCs. A loss-of-function assay for protein tyrosine phosphatase non-receptor type 2 (PTPN2) was performed to explore the involvement of PTPN2/signal transducer and activator of transcription 3 (STAT3) signaling on the therapeutic benefit of hUCMSCs in EAT. hUCMSC treatment significantly alleviated inflammation, reduced serum thyroid antibody levels, and decreased the ratios of IL-17α + /CD25 + FOXP3 + cells and serum IFN-γ/IL-4 in EAT rats. Furthermore, hUCMSC treatment upregulated PTPN2 protein expression in splenic lymphocytes of EAT rats as well as enhanced the PTPN2 protein level and attenuated phosphorylation of STAT3 in CD4 + T cells in vitro. Importantly, knockdown of Ptpn2 significantly reversed hUCMSC-mediated suppression of cell proliferation and hUCMSC-induced alterations in the expression of inflammatory cytokines in CD4 + T cells. Thus, hUCMSC treatment alleviates thyroid inflammation and the CD4 + T cell imbalance in EAT via PTPN2/STAT3 signaling, serving as a promising therapeutic approach for autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), one of the most common autoimmune diseases among women of reproductive age, is closely associated with reproductive failure and other obstetric complications. However, effective clinical strategies for the management of pregnant women with AIT are limited. It has been shown that Prunella vulgaris (PV), a traditional herbal medicine, can ameliorate AIT and other common thyroid disorders. Therefore, using an experimental autoimmune thyroiditis (EAT) rat model, we investigated the potential effects of PV on AIT-related pregnancy outcomes. According to the administered dose of PV, EAT rats were randomly divided into the untreated EAT and PV-treated EAT groups. We found that thyroid peroxidase antibody and thyroglobulin antibody serum levels and the inflammatory infiltration of the thyroid were reduced in all PV-treated groups. Increased splenic Tgfb1 mRNA levels and Treg cell proportions were associated with decreased Th1/Th17 cell proportions, and Ifng mRNA levels were reduced in rats that received low and medium doses of PV. Moreover, in the low-dose PV group, fetal development retardation and placental injuries were reversed. Overall, our findings indicated that PV could alleviate AIT and improve pregnancy outcomes in EAT rats by downregulating Th1/Th17 immune responses and inducing Treg cell proliferation., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To observe the effect of herb-partitioned moxibustion (HPM) on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis (EAT) rats., Methods: Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, HPM group and western medicine (Med) group. EAT model rats were prepared by a combined immunization with complete and incomplete Freund's adjuvant emulsified with porcine thyroglobulin and iodine. Rats in the HPM group were treated with HPM, while rats in the Med group were treated with levothyrocine (1 μg/2 mL) by gavage. HE staining was used to observe the pathological morphological changes of thyroid tissue, ELISAs was uaed to detect the serum concentrations of TGAb, TPOAb, FT3, FT4, TSH. We then performed high-throughput miRNA sequencing to analyse the miRNA expression profiles in the thyroid tissues, followed by a bioinformatics analysis. RT-qPCR was used to verify the identified differentially expressed miRNAs., Results: HPM improved the thyroid tissue morphology and reduced serum TPOAb, TGAb, TSH concentration in EAT rats (P < 0.05), but with no obvious effect on FT3 and FT4 concentration. While the TSH, FT3 and FT4 concentration was significantly changed in the Med group (P < 0.01 or P < 0.05) compared with that of EAT group. Sequencing results showed that a total of 17 miRNAs were upregulated, and 4 were downregulated in the EAT rats, in which the expression levels of miR-346 and miR-331-5p were reversed by HPM. The target genes of the miRNAs that regulated by HPM were associated with a variety of immune factors and immune signals. RT-qPCR verification showed that the expression of miRNA-346 and miRNA-331-5p was consistent with the sequencing results., Conclusions: HPM could regulate the the expression of miRNA-346 and miRNA-331-5p, then act on their target genes to immune and inflammation-related pathways, which may be one of the mechanisms of HPM on EAT rats.

Aims: This study aimed to investigate the therapeutic effect of Cordyceps sinensis-derived fungus Isaria felina on experimental autoimmune thyroiditis (EAT)., Methods: A NaI-induced EAT mouse model was established. The mice received oral administration of vehicle, low-dose Isaria felina (300 mg/kg), or high-dose Isaria felina (600 mg/kg) once a day for four weeks before euthanasia. Enzyme-linked immunosorbent assays (ELISA) was performed to measure serum thyroid-stimulating hormone (TSH) levels, thyroid antibodies, and cytokines. Hematoxylin and eosin (H&E) staining was conducted to assess histopathological changes in the thyroid tissue samples of mice. TUNEL and Bcl-2 immunohistochemistry (IHC) were performed to evaluate cell apoptosis, and cleaved caspase-3 IHC was performed to detect the relative expression in the thyroid tissue samples., Results: Compared with KIO 3 and KI water, NaI water consumption successfully induced EAT in mice, as evidenced by significantly increased circulating TSH and thyroid antibody levels, along with typical histopathological abnormalities of autoimmune thyroiditis (AIT) in the thyroid tissue samples. Compared with vehicle or low-dose Isaria felina, high-dose Isaria felina treatment resulted in significant reductions in white cell counts and circulating TSH, thyroid antibody, and cytokine levels of EAT mice. High-dose Isaria felina also alleviated histopathological abnormalities and attenuated TUNEL staining, Bcl-2 protein expression, and cleaved caspase-3 expression in the thyroid tissue samples., Conclusion: High-dose Isaria felina treatment alleviates thyroid inflammation and cell apoptosis in EAT, serving as a novel, promising therapeutic agent for AIT., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART)., Methods: We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results., Results: Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P < .0001) and live birth rate (OR = 3.19, 95% CI [1.13, 9.04], I2 = 0.0%, P = .03) of ATA-positive women compared with control group. However, it seems that glucocorticoid showed no significant difference in the abortion rate (OR = 0.62, 95% CI [0.09, 4.32], I2 = 35%, P = .64) and oocyte recovery (OR = 2.26, 95% CI [-1.46, 5.99], I2 = 79%, P < .0001) between the 2 groups., Conclusions: Glucocorticoid may improve the pregnancy outcomes of ART women with ATA positive, but there is no significant reduction in the risk of miscarriage. Due to the limited enrolled references, glucocorticoid adjuvant therapy should be applied after more randomized controlled trials., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Problem: Our study aims to investigate whether the anti-thyroperoxidase antibody (TPO-Ab) and TSH level in euthyroid women have any association with reproductive outcomes after the ART cycle., Methods of Study: A total of 1107 patients who were enrolled in the study were divided into four groups based on serum TSH level and TPO-Ab status: group A, 0.3 ≤ TSH < 2.5 mIU/L and TPO-Ab - ; group B, 0.3 ≤ TSH < 2.5 mIU/L and TPO-Ab + ; group C, 2.5 ≤ TSH < 4.2 mIU/L, and TPO-Ab - ; and group D, 2.5 ≤ TSH < 4.2 mIU/L, TPO-Ab + . The differences in ART cycles and pregnancy outcomes were analyzed between study groups., Results: The fertilization rate in group D (73%) was significantly lower than that in groups A (83% P < .001), B (84% P = .001), and C (82% P = .002). The biochemical pregnancy rates of groups B (7%) and D (12%) were significantly higher than those of group A (2%) (P = .028 and P = .017, respectively). TPO-Ab was related to a higher biochemical pregnancy rate (P = .002, OR = 5.311, 95% CI 1.859-15.169) and TSH over 2.5 mIU/L was related to higher ICSI rate (P = .001, OR = 1.759, 95% CI 1.250-2.476) by logistic regression analysis. The receiver operating characteristic (ROC) also verified the results., Conclusion: The impacts of TSH ≥ 2.5 mIU/L on the intracytoplasmic sperm injection (ICSI) rate, TSH ≥ 2.5 mIU/L and TPO-Ab + on the fertilization rate, and TPO-Ab + on the biochemical pregnancy rate, rather than the effect on abortion, clinical pregnancy, and live birth, were emphasized., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Riedel thyroiditis (RT) is a rare inflammatory autoimmune disease that is often a clinically diagnostic dilemma because of its insidious presentation and nonspecific symptoms., Objective: The aim of the present systematic review and meta-analysis is to clarify the presentation, management, and outcomes of RT., Study Selection: A systematic search of PubMed/MEDLINE and Web of Science was conducted to identify relevant reports published up to September 2019., Data Extraction: First author, country, patient sex, ethnicity, presentation, biochemical status, duration of symptoms, histology, treatment, follow-up duration, and short- and long-term outcomes., Data Synthesis: Data from 212 RT patients were retrieved. The mean age was 47 years with a predominantly female population (81%). Neck swelling (89%), dyspnea (50%), and neck pain (41%) were the most common presenting symptoms. Inflammatory markers were elevated in 70% to 97% and thyroid antibody positivity was present in less than 50%. Up to 82% underwent surgical intervention, with the most common being total thyroidectomy in 34% of individuals. Glucocorticoids were used in 70% of individuals with median duration 3 months. Prognosis was reasonable with 90% having resolution or improvement of symptoms., Conclusions: This analysis is the largest and most comprehensive to date of RT and provides clinicians with vital information on the common presentation features that may alert to the diagnosis and highlight management options., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Autoimmune thyroid disease (AITD) is one of the most frequent autoimmune disorders. However, the pathogenesis of AITD has not been fully elucidated. Recently, accumulating evidence has demonstrated that abnormal expression of noncoding RNAs (ncRNAs) is closely related to the etiopathogenesis of AITD. microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) are 3 major groups of ncRNAs that are attracting increasing attention. Herein, we summarized our present knowledge on the role of miRNAs, lncRNAs, and circRNAs in AITD. This review focused on the importance of ncRNAs in development of the most prevalent AITD, such as Hashimoto disease and Graves' diseases. Altogether, the main purpose of this review is to provide new insights in the pathogenesis of AITD and the possibility of developing novel potential therapeutic targets., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The association between autoimmune atrophic gastritis and thyroid disorders has been observed since the early 1960s and the expression "thyrogastric syndrome" was coined to indicate the presence of thyroid autoantibodies or autoimmune thyroid disease in patients with pernicious anemia, a late clinical stage of autoimmune atrophic gastritis. More recently, it was confirmed that autoimmune thyroid disorders, in particular Hashimoto's thyroiditis, may be frequently associated with other organ-specific, immune-mediated disorders, such as autoimmune atrophic gastritis or celiac disease. The association of Hashimoto's thyroiditis with autoimmune atrophic gastritis or celiac disease in adult patients is currently considered part of the polyglandular autoimmune syndromes which include several autoimmune disorders associated with an autoaggressive impairment of endocrine glands. From a clinical point of view, the thyro-entero-gastric autoimmunity may lead to potentially serious consequences like anemia, micronutrients deficiencies, and drugs malabsorption, as well as to an increased risk for malignancies. These alterations may frequently present in an underhand manner, with consequent diagnostic and treatment delays. Many aspects of the association between thyroid, gastric and intestinal autoimmune diseases still await clarification. The present review focuses on the embryological, genetic and pathophysiological aspects of thyro-entero-gastric autoimmunity. In particular, the current diagnostic criteria of autoimmune thyroid disease, autoimmune atrophic gastritis, and celiac disease are reviewed, along with the evidences for their association in poly-autoimmunity syndromes. The benefits of proactive screening of autoimmune thyroid disorders in patients with autoimmune gastritis or enteropathy and viceversa are also discussed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A Th1 immune-preponderance has been shown in the immunopathogenesis of autoimmune thyroiditis (AT), Graves' disease (GD) and Graves' Ophthalmopathy (GO), in which the Th1-chemokines (CXCL9, CXCL10, CXCL11), and their (C-X-C)R3 receptor, have a crucial role. Methimazole, and corticosteroids have been shown to modulate these chemokines; several efforts have been done to modulate the autoimmune reaction with other drugs, i.e. PPAR-γ, or -α ligands, or antibodies, or small molecules directed against CXCL10, or CXCR3. Antigen-specific therapy for GD, by inducing T cell tolerance through an immunization with TSH-R peptides, has been published. Drugs targeting cytokines [anti-TNFα (Etanercept), and anti-IL-6 (Tocilizumab)], and RTX (a chimeric monoclonal antibody vs. CD20) have been used in GO, with promising results. Teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) has been investigated in a trial, showing it was very effective in GO patients. Still, more studies are needed for new therapies targeting autoimmune thyroid disorders., Competing Interests: Declaration of Competing Interest The Authors have nothing to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto thyroiditis (HT), are the most prevalent organ-specific autoimmune diseases, but their pathogenesis is still incompletely understood. The PD-1/PD-L1 pathway is an important mechanism of peripheral tolerance that has not been investigated in AITDs. Here, we report the analysis of the expression of PD-1, PD-L1 and PD-L2 in PBMCs, infiltrating thyroid lymphocytes (ITLs) and in thyroid follicular cells (TFCs) in GD, HT and multinodular goiter (MNG) patients and healthy controls PBMCs (HC). By combining flow cytometry, tissue immunofluorescence and induction experiments on primary and thyroid cell line cultures, we show that: 1) while PD-1+ T cells are moderately expanded in PBMCs from GD vs HC, approximately half of T cells in the infiltrate are PD-1+ including some PD-1 hi ; 2) PD-L1, but not PD-L2, is expressed by 81% of GD glands and in 25% of non-autoimmune glands; 3) PD-L1, was expressed by TFCs in areas that also contain abundant PD-1 positive T cells but; 4) co-localization in TFCs indicated only partial overlap between the smaller areas of the PD-L1+ and the larger areas of HLA class II+ expression; 5) IFNγ is capable of inducing PD-L1 in >90% of TFCs in primary cultures and cell lines. Collectively these results indicate that the PD-1/PD-L1 axis is operative in AITD glands and may restrain the autoimmune response. Yet the discrepancy between easy induction in vitro and the limited expression in vivo (compared to HLA) suggests that PD-L1 expression in vivo is partially inhibited in GD and HT glands. In conclusions 1) the PD-1/PD-L1 pathway is activated in AITD glands but probably not to the extent to inhibit disease progression and 2) Thyroid autoimmunity arising after PD-1/PD-L1 blocking therapies in cancer patients may result from interfering PD-1/PD-L1 tolerance mechanism in thyroid with minimal (focal) thyroiditis. Finally acting on the PD-1/PD-L1 pathway could be a new approach to treat AITD and other organ-specific autoimmunity in the future., (Copyright © 2019. Published by Elsevier Ltd.)

Previous evidence suggested that lymphocytic thyroiditis (LT) was a variant of Hashimoto's thyroiditis (HT), thus the aim of the current study is to quantify structural changes in histological specimens taken from HT and LT patients. A total of 600 images containing a single lymphocyte nucleus (300 nuclei per group) were obtained from 20 patients with HT and LT. In order to quantify changes in the nuclear architecture of investigated lymphocytes, the fractal dimension (FD) and some gray-level co-occurrence matrix texture parameters (angular second moment, inverse difference moment, contrast, entropy, and correlation) were calculated for each nucleus. A statistically significant difference in the FD of the "binary-outlined" nucleus and that of the corresponding "black-and-white" nucleus was detected between HT and LT lymphocyte nuclei. In addition, there was also a statistically significant difference in contrast and correlation between HT and LT lymphocyte nuclei. In conclusion, the results of this study suggested that there was a difference in structural complexity between investigated lymphocyte nuclei; additionally, LT lymphocytes possessed probably more complex texture and larger variations as well as more asymmetrical nuclei compared with HT lymphocytes. Accordingly, these findings indicate that LT is probably not a variant of HT; however, more complex studies are necessary to estimate differences between these types of thyroiditis.

What Is Known and Objective: Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 μg daily as l-selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT., Methods: Seventy-one (71) children and adolescents, with a mean age of 11.3 ± 0.3 years (range 4.5-17.8), diagnosed with AT (antibodies against thyroid peroxidase [anti-TPO] and/or thyroglobulin [anti-Tg] ≥60 IU/mL, euthyroidism or treated hypothyroidism and goitre in thyroid gland ultrasonography) were randomized to receive 200 μg l-selenomethionine or placebo daily for 6 months. Blood samples were drawn for measurement of serum fT4, TSH, anti-TPO and anti-Tg levels, and thyroid gland ultrasonography was performed at the entry to the study and after 6 months of treatment., Results and Discussion: At the end of the study, a statistically significantly higher reduction in anti-Tg levels was observed in the Se group compared to the placebo group (Δ: -70.9 ± 22.1 vs -6.7 ± 60.6 IU/mL, P = 0.021). Although anti-TPO levels were also decreased in the Se group, this change was not statistically different from that of the control group (Δ: -116.2 ± 68.4 vs +262.8 ± 255.5 IU/mL, P = 0.219). No significant difference in thyroid gland volume was observed between the two study groups (P > 0.05)., What Is New and Conclusion: In this original study, organic Se supplementation appears to reduce anti-Tg levels in children and adolescents with AT., (© 2018 John Wiley & Sons Ltd.)

While overt hypothyroidism is a well-known risk factor for infertility, the association of subclinical hypothyroidism (SCH) or thyroid autoimmunity and reproductive failure has been still not elucidated. In this literature review, the current data on the effect of SCH and/or thyroid autoimmunity and human reproduction is presented. The main ART outcome measures are as follows: number of oocytes retrieved, fertilization rate, implantation rate, clinical pregnancy rate per embryo transfer, embryo quality, miscarriage rate, and live birth rate. Current guidelines on the management of women with SCH and/or thyroid autoimmunity undergoing ART cycles will be presented in this review.

Years of researches have demonstrated that the imbalance of Th17 and Tregs contribute to the thyroid autoimmunity and the severity of autoimmune thyroid disease (AITD). The underlying mechanism comprises inherent genetic predisposition, abnormality of Th17 and Treg related biological molecules, and gut microbiota disorder. New therapeutic strategies have been developed to improve the Th17/Treg equilibrium, including regulation of intracellular signaling pathways, neutralization of Th17-related cytokines, as well as manipulation of Th17 and Treg specific transcription factors. Although a few of these agents are applied into AITD, the clinic prospect is promising., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.

Objective: To quantify clinical outcome in patients with steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) after the acute phase and explore potential associations of initial serum thyroid peroxidase antibody titers (TPO-Abs) with outcome., Materials and Methods: Retrospective chart review of patients diagnosed with SREAT between 01/2005 and 05/2014 in a tertiary care center and followed in an affiliated autoimmune outpatient clinic. Outcome was quantified using the extended Glasgow Outcome Scale (GOS-E). We calculated Pearson's correlation coefficients to quantify associations with clinical outcome at follow-up., Results: Among 134 patients with encephalopathy of unknown etiology, we identified 13 patients diagnosed with SREAT. In two patients, the diagnosis was revised at subsequent hospitalization (NMDA-R encephalitis and adult-onset Still's disease). The median follow-up time was 11 months, and the median GOS-E was 6 (range 3-8). Higher serum TPO-Ab-titers correlated with more favorable outcomes (Pearson coefficient 0.65, P = 0.03)., Conclusion: A correlation between TPO-Ab-titers and outcome has not been reported previously and challenges the notion of a mere bystander role of TPO-Abs in SREAT., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes., (© Polish Society for Pediatric Endocrinology and Diabetology.)

This study aimed to identify the beneficial effects of adipose tissue-derived mesenchymal stem cells (ASCs) and ASCs that overexpress the CTLA4Ig gene (CTLA4Ig-ASCs) on established autoimmune thyroiditis and to examine changes in clinical chemistry parameters and the presence of humoral responses upon repeated long-term administration of autologous ASCs. This study also aimed to acquire desirable results in a preclinical study by using large-sized lab animals and applying ASCs that overexpress therapeutic genes. Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Experimental dogs were divided into five groups: (i) ASC IT + IV, (ii) ASC IV, (iii) CTLA4Ig-ASC IT + IV, (iv) CTLA4Ig-ASC IV, and (v) control IT + IV (saline only), and they received intrathyroidal (IT; 10 million cells/250 µl saline per thyroid) administration one time or intravenous (IV; 20 million cells/5 ml) administration seven times within a 101-day period. Blood samples were collected every week, and thyroids were harvested on days 104-106. After serial ASC or CTLA4Ig transplantation, the levels of canine thyroglobulin autoantibodies (TgAA) in serum and the infiltration of T-lymphocytes between the follicles of the thyroid glands were decreased. The expression of FoxP3 in submandibular lymph nodes was significantly increased. Repeated long-term administration of autologous ASCs or CTLA4Ig-ASCs did not generate changes in clinical chemistry parameters or humoral responses.The TgAA test can detect autoimmune thyroiditis years before clinical signs of hypothyroidism occur. Thus, ASC and CTLA4Ig-ASC transplantation in that period can be attractive candidates to ameliorate autoimmune thyroiditis and prevent the development of hypothyroidism.

B cells are required for development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice where they function as important APCs for activation of CD4(+) T cells. Depletion of B cells using anti-CD20 effectively inhibits SAT development. The goals of this study were to characterize the B cells that migrate to thyroids in SAT, and to determine whether anti-CD20 effectively targets those B cells in mice with established SAT. The results showed that most thyroid-infiltrating B cells in mice with SAT are follicular (FO) B cells. Expression of CD80, CD86, and CD40 was significantly increased on FO, but not marginal zone, splenic B cells after SAT development. Thyroid-infiltrating and peripheral blood B cells had lower expresion of CD20 and CD24 compared with splenic and lymph node FO B cells. Despite reduced CD20 expression, anti-CD20 depleted most B cells in thyroids of mice with established SAT within 3 d. B cell depletion in thyroids of mice given anti-CD20 was more complete and longer lasting than in spleen and lymph nodes and was comparable to that in blood. Circulation of B cells was required for effective and rapid removal of B cells in thyroids because preventing lymphocyte egress by administration of FTY720 abrogated the effects of anti-CD20 on thyroid B cells. Therefore, the FO subset of B cells preferentially contributes to SAT development and persistence, and anti-CD20 targeting of FO B cells effectively eliminates B cells in the target organ even though thyroid B cells have decreased CD20 expression.

Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations.

Background: Even though the presence of antithyroglobulin antibodies (TgAbs) represents a significant problem in the follow-up of patients with differentiated thyroid cancer (DTC), the current guidelines on the management of DTC that have been published in recent years contain no text concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker., Aim: An international group of experts from the European Thyroid Association Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues., Results: This clinical opinion article provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients., Conclusion: We were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients.

This overview of the thyroid autoimmunity in human presents the various facets of a very common pathology. Focus is rather on fundamental than clinical aspects, although some specific clinical situations are discussed. Epidemiology, pathophysiology and pathology of AITD are detailed. One of the peculiarities of AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and hyperthyroid Graves' disease. The latter is characterised by the presence of a unique type of autoantibodies, the anti-TSH receptor antibodies. Those are capable to activate the TSH receptor leading to the gland hypertrophy and hyperfunction. On the contrary, the autoimmune thyroiditis processus progressively and slowly tends to the necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis, postpartum thyroiditis and silent thyroiditis are also described. This review, which is not exhaustive, aims at providing a wide scope on the AITD, a basis from which the interested reader or the specialist will be able to find routes towards deeper knowledge., (Copyright © 2012. Published by Elsevier Masson SAS.)

We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative. This is the first case of autoimmune thyroiditis found in such a young patient with pre-existing nephrotic syndrome ever described in literature. This association is random because nephrotic syndrome does not have an autoimmune pathogenesis and the genes involved in autoimmune thyroiditis are not related to those of nephrotic syndrome.

Ethnopharmacological Relevance: Modified Haizao Yuhu Decoction (MHYD), based on clinical experience, has been used for approximately 500 years and famous for its efficiency in treating thyroid-related diseases., Aim of the Study: To investigate therapeutic effects of MHYD on thyroid-related autoantibodies and thyroid hormone in experimental autoimmune thyroiditis (EAT) rats, and to provide evidence for the immunomodulatory potential during antigenmediated immunostimulation., Materials and Methods: The effect of MHYD was investigated in EAT rats induced by subcutaneous injection of porcine thyroglobulin with Freund's adjuvant (complete and incomplete, CFA and IFA). MHYD was fed to EAT rats daily at a dose of 100mg/kg for 10 weeks. The presence of mononuclear cell infiltration in thyroid tissues were examined to assess the severity of EAT. The levels of serum T3, T4, TgAb and TPOAb were determined by radioimmunoassay and protein expressions of TRAIL were detected by immunohistochemistry., Results: MHYD exhibited a significant protective effects by reversing serum T3, T4, TgAb and TPOAb levels, histopathological changes and TRAIL protein expression of thyroid in EAT model rats. Sargassum fusiforme and Radix Glycyrrhiza in the formulation could be responsible for the immunomodulatory effects of MHYD., Conclusions: These results showed MHYD playing a role as an immunomodulator and TRAIL inhibitor during antigenmediated immunostimulation, may warrant further evaluation as a possible agent for the treatment of Hashimoto's thyroiditis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Encephalopathy associated with autoimmune thyroid disease is a rare condition presenting in the setting of autoimmune thyroid disease and characterized by unspecific neurological and/or psychiatric symptoms. Bearing in mind the currently prevailing lack of consensus on the most appropriate nomenclature and diagnostic criteria for this condition and the implications that this lack undeniably has on clinical practice, it is obvious that an international and multidisciplinary agreement among clinicians should arrive at the most appropriate definition and terminology of encephalopathy occurring in patients with autoimmune thyroid disease. Concomitantly, efforts must be made to uncover the pathogenetic link between thyroid autoimmunity and the occurrence of encephalopathy.

Objective: Autoimmune chronic thyroiditis (ACT) is characterized by lymphocyte infiltration in the thyroid gland and the presence of antithyroid antibodies in serum. Medical treatment does not affect antibody levels and treatment decision is not definite yet for the euthyroid patients. We aimed to evaluate cardiac autonomic function and global left ventricular performance in autoimmune euthyroid chronic thyroiditis and determine the need for medical treatment., Method: We studied 30 ACT patients and 25 healthy control subjects. Cardiac autonomic function is evaluated by heart rate recovery (HRR). Global left ventricular performance is evaluated by two-dimensional echocardiography and pulsed-wave tissue Doppler echocardiography., Results: There was no difference between patients and controls with respect to clinical and biochemical parameters except hemoglobin (13.67 ± 1.25 g/dL, 14.51 ± 1.35 g/dL, p:0.047) and low density lipoprotein (120.71 ± 24.91 mg/dL, 100.55 ± 14.73 mg/dL, p: 0.003). Tei index was significantly higher in ACT group (0.521 ± 0.074, 0.434 ± 0.034, P < 0.0001). E'/A' was found to be significantly lower (1.234 ± 0.42, 1.750 ± 0.291, P < 0.0001) and E/E' was found to be higher than the controls (8.482 ± 0.449, 6.039 ± 0.209, P < 0.0001). HRR was significantly lower than the controls (20 ± 4 BPM, 30 ± 8 BPM, P < 0.0001)., Conclusion: Although left ventricular performance is found to be normal by conventional echocardiographic methods, it is found to be impaired when Tei index and tissue Doppler parameters are used. Cardiac autonomic function is also impaired in ACT patients. As a result of these cardiac changes, medical treatment may be considered earlier, even at the euthyroid stage., (© 2010, Wiley Periodicals, Inc.)

Background: Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene-transduced ATMSC on autoimmune thyroiditis., Methods: Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene-transduced human ATMSC (CTLA4Ig-MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3-week period. Blood and tissue samples were collected 1 week after the last cell transplantation., Results: The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig-MSC group was considerably lower than those in other groups. In culture supernatant of LPS-stimulated spleen cells, both of the MSC-treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig-MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC-treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down-regulating Th1 cytokines., Conclusion: Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background and Objectives: Chronic autoimmune thyroiditis (CAT) remains the most common cause of acquired hypothyroidism. There is currently no therapy that is capable of regenerating CAT-damaged thyroid tissue. The objective of this study was to gauge the value of applying low-level laser therapy (LLLT) in CAT patients based on both ultrasound studies (USs) and evaluations of thyroid function and thyroid autoantibodies., Study Design/materials and Methods: Fifteen patients who had hypothyroidism caused by CAT and were undergoing levothyroxine (LT4) treatment were selected to participate in the study. Patients received 10 applications of LLLT (830 nm, output power 50 mW) in continuous mode, twice a week, using either the punctual technique (8 patients) or the sweep technique (7 patients), with fluence in the range of 38-108 J/cm(2). USs were performed prior to and 30 days after LLLT. USs included a quantitative analysis of echogenicity through a gray-scale computerized histogram index (EI). Following the second ultrasound (30 days after LLLT), LT4 was discontinued in all patients and, if required, reintroduced. Triiodothyronine, thyroxine (T4), free T4, thyrotropin, thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies levels were assessed before LLLT and then 1, 2, 3, 6, and 9 months after LT4 withdrawal., Results: We noted all patients' reduced LT4 dosage needs, including 7 (47%) who did not require any LT4 through the 9-month follow-up. The LT4 dosage used pre-LLLT (96 +/- 22 microg/day) decreased in the 9th month of follow-up (38 +/- 23 microg/day; P < 0.0001). TPOAb levels also decreased (pre-LLLT = 982 +/- 530 U/ml, post-LLLT = 579 +/- 454 U/ml; P = 0.016). TgAb levels were not reduced, though we did observe a post-LLLT increase in the EI (pre-LLLT = 0.99 +/- 0.09, post-LLLT = 1.21 +/- 0.19; P = 0.001)., Conclusion: The preliminary results indicate that LLLT promotes the improvement of thyroid function, as patients experienced a decreased need for LT4, a reduction in TPOAb levels, and an increase in parenchymal echogenicity., ((c) 2010 Wiley-Liss, Inc.)

An autoimmune thyroiditis represents the main reason of hypothyroidism, defined as a lack of thyroid hormone. This autoimmune process results in destruction of functioning thyroid follicles. While subclinical or latent hypothyroidism is defined on the basis of laboratory values (an elevation of TSH with normal peripheral hormone levels), the typical signs and symptoms are associated with hypothyroidism. In about 80% of cases antibodies against thyroid peroxidase can be measured, but only in about 40-50% of cases antibodies against thyroglobulin are detectable. If hypothyrodism has been diagnosed, substitution with levothyroxine should be initiated, with the therapeutic goal to decrease TSH level to the lower normal range. In cases of subclinical hypothyroidism, levothyroxine medication should be started in patients with a high TSH value, positive antibodies and/or the typical ultrasound of autoimmune thyroiditis. However, substitution with levothyroxine in any case of elevated TSH values should be avoided.

Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves' disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs.

Background: The present study aimed to determine the effect of canine CTLA4Ig on canine autoimmune thyroiditis. In a previous study, we established a canine model of autoimmune thyroiditis by immunizing normal dogs with bovine thyroglobulin. An in vitro study using recombinant CTLA4Ig revealed that this protein can inhibit the expression of Th1-type cytokines and the pro-inflammatory cytokines tested., Methods: As a result of the in vitro study, we constructed therapeutic CTLA4Ig/silica-nanoparticles and applied them to the treatment of experimentally induced canine autoimmune thyroiditis., Results: Gene therapy resulted in significant reductions in anti-canine-thyroglobulin autoantibody titer, anti-T4 antibody titer and T-cell proliferation against thyroglobulin and in the mRNA expressions of interleukin-18 in fresh peripheral blood mononuclear cells (PBMC) from all dogs. There was also a significant reduction compared to day 0 in tumor necrosis factor-alpha and interferon-gamma levels in the supernatant from cultured PBMC., Conclusions: The CTLA4Ig-induced suppression of Th1 cytokines is relatively more significant than it appears because autoimmune thyroiditis is a Th1-polarized disease. Thus, CTLA4Ig can improve Th1/Th2 cytokine balance in autoimmune thyroiditis by downregulating Th1 cytokines.

In Chinese, autoimmune thyroid disease (AITD) is very common but lymphoma of the thyroid is a rare disease. Southern Chinese AITD is common in females and is strongly linked to the HLA haplotype A2B46DR9. We studied the HLA association, aberration p15, p16 and p73 promoter methylation and microsatellite instability in Chinese primary thyroid lymphoma patients to elucidate their relationship with AITD and the relationship between thyroid diffuse large cell lymphoma (DLCL) and marginal zone lymphomas (MZL). Despite a female preponderance (8:1) and the finding of cases with histological and immunological evidence of AITD, a significant HLA association was not found. MSI was absent, but aberrant promoter methylation was found in both thyroid MZL and DLCL and p73 methylation was unexpectedly common.

Context: Activation-induced cell death (AICD) is a major mechanism in the regulation of peripheral tolerance, and caspase-3 represents its major executioner. AICD impairment contributes to the persistence of autoreactive T cells, and defective AICD has been reported in autoimmune thyroiditis as well as in type 1 diabetes mellitus., Objective: The objective of this study was to evaluate the involvement of caspase-3 in the regulation of AICD resistance in thyroid and polyendocrine autoimmunity. DESIGN/SETTINGS/PATIENTS/INTERVENTION: Caspase-3 expression was analyzed in peripheral blood lymphocytes from 26 adults (A-AT) and 25 children (Y-AT) affected by autoimmune thyroiditis and 13 individuals affected by chronic autoimmune thyroiditis plus Addison's disease [autoimmune polyendocrine syndrome-2 (APS-2)] in comparison with 32 age-matched normal control subjects (NC)., Outcome Measures: Caspase-3 mRNA expression in peripheral T cells was evaluated by quantitative real-time PCR; protein expression of both procaspase-3 and activated caspase-3 by Western blot analysis was followed by scanning densitometry., Results: Caspase-3 mRNA expression was significantly reduced in resting lymphocytes from both A-AT (P = 0.001) and Y-AT (P = 0.016) compared with NC. After lymphocyte activation, protein levels of caspase-3 active form were significantly reduced in A-AT (P = 0.023) and Y-AT (P = 0.001) compared with NC. The APS-2 group displayed characteristics similar to the A-AT group because both caspase-3 mRNA and protein active form levels were significantly reduced compared with NC (P = 0.004 and 0.002, respectively)., Conclusion: Our data show that peripheral lymphocytes of subjects affected by thyroid autoimmunity or APS-2 show defective expression of the major executioner of AICD, thus potentially contributing to AICD resistance and to the development of autoimmunity.

Objectives: The impact of dental amalgam removal on the levels of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in patients with autoimmune thyroiditis (AT) with and without mercury allergy., Methods: Thirty-nine patients with AT were tested by an optimized lymphocyte proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury. Patients were divided into two groups: Group I (n = 12) with no hypersensitivity to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam fillings were removed from the oral cavities of 15 patients with hypersensitivity to mercury (Group IIA) and left in place in the remaining 12 patients (Group IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were determined in all groups at the beginning of the study and six months later., Results: Compared to levels at the beginning of the study, only patients with mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or without mercury hypersensitivity (Group I and Group IIB) who did not replace amalgam did not change., Conclusion: Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

An 18-month-old boxer was presented for investigation of profound lethargy, and primary hypothyroidism was diagnosed. A strong antithyroglobulin antibody titre was also present, indicating lymphocytic (immune-mediated) thyroiditis as the cause of hypothyroidism. A concurrent protein-losing glomerulonephropathy was also detected, although the aetiology could not be determined at initial presentation. Thyroid replacement and dietary therapy were prescribed. The dog improved clinically for approximately 12 months when it was re-presented with poorly controlled hypothyroidism and renal failure. Postmortem examination confirmed the presence of lymphocytic-plasmacytic thyroiditis, in conjunction with membranoproliferative glomerulonephritis and renal failure.

Objective: Serum CXCL10 (an interferon-gamma-inducible chemokine) levels (sCXCL10) are increased in several autoimmune conditions, including Graves' disease (GD) and autoimmune thyroiditis (AT). Longitudinal assessment of sCXCL10 in autoimmune hypo- or hyperthyroidism has not yet been performed., Design and Methods: We longitudinally assayed sCXCL10 in the following groups: thirty-three GD and 11 toxic nodular goiter (TNG) patients when hyperthyroid (Hyper) and when reaching euthyroidism (Eu) with methimazole therapy (MMI) sixty-six AT (33 hypothyroid (Hypo) and 33 Eu) patients, basally and after reaching EU (for Hypo) with levothyroxine (L-T4) therapy twenty-two patients with thyroid cancer (CA) under L-T4-suppressive treatment, of whom 11 were re-evaluated after L-T4 withdrawal for diagnostic WBS, and 11 after recombinant TSH (rhTSH) administration thirty-three healthy controls., Results: At initial evaluation, Hyper GD and AT (Hypo significantly higher than Eu) showed significantly higher mean sCXCL10 than all other groups. MMI treatment led to a significant decrease in sCXCL10 only in GD (not in TNG), while restoration of Eu, in Hypo AT, by L-T4 was not accompanied by significant sCXCL10 change. CA showed sCXCL10 comparable to controls, and both Hypo after L-T4 withdrawal and rhTSH injection had no effect on sCXCL10., Conclusions: Treatment of Hyper leads to a significant decrease in sCXCL10 only in GD, and this probably depends upon the MMI immunomodulatory effect. L-T4 correction of Hypo is not accompanied by significant modification of sCXCL10 in AT. Increased sCXCL10 is not associated with Hyper or Hypo per se, but is specifically sustained by the autoimmune inflammatory event occurring in both GD and AT.

We propose non-pharmacological treatment of autoimmune thyroid diseases--interval hypoxic training (IHT). The course of hypoxytherapy improves the patients's condition, normalizes the level of thyroid hormones in the blood, has an immunomodulating action. Positive hormonal, immunological and clinical effects observed in patients with autoimmune pathology after IHT validate its use in autoimmune thyropathy both in combination with conventional drug therapy and as monotherapy.