Current Concepts in Endocrinology for Clinicians and Medical Students. Hashimoto’s Thyroiditis: clinical and subclinical thyroid dysfunction

Hashimoto’s thyroiditis (HT) is an autoimmune and inflammatory disease in which antibodies are directed against the thyroid gland leading to chronic inflammation and hypothyroidism. The autoimmunity against thyroid antigens can be associated to genetic background and environmental factors. Thyroid peroxidase (TPO) and thyroglobulin (TG) are the major autoantigens for characterizing the disease. HT is related to the activation of autoreactive CD4+ T cells, CD8+ cytotoxic T cells and antithyroid antibody producing-B cells. Among several cytokines related to the pathogenesis of HT, a proliferation-inducing ligand (APRIL) has been studied in the context of the establishment and/or maintenance of autoimmune diseases. The role of APRIL in the pathogenesis of HT is still poorly understood. Therefore, the present study aimed to compare APRIL serum concentration in HT patients and healthy donors by ELISA. We observed a significant decrease in APRIL concentration in HT patients when compared to the control group, and a positive correlation between APRIL level and age. Our results suggest that the APRIL molecule can compose the cytokine profile along the inflammatory response in HT, however, other investigations should be proposed to understand its molecular mechanisms via specific receptors and other regulatory loops.

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The Expression of T Cell FOXP3 and T-Bet Is Upregulated in Severe but Not Euthyroid Hashimoto’s Thyroiditis

Mediators of Inflammation ◽

10.1155/2016/3687420 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Stana Tokić ◽

Mario Štefanić ◽

Ljubica Glavaš-Obrovac ◽

Sonja Jaman ◽

Eva Novosadová ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Hashimoto’S Thyroiditis ◽

Hormone Replacement ◽

Study Groups ◽

Hashimoto's Thyroiditis ◽

Foxp3 Mrna ◽

Expression Levels ◽

Treg Subset ◽

Mrna Expression Levels

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P<0.01) and thyroxine-supplemented patients (2.5-fold, P<0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P<0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.

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The Link between Graves’ Disease and Hashimoto’s Thyroiditis: A Role for Regulatory T Cells

Endocrinology ◽

10.1210/en.2007-1024 ◽

2007 ◽

Vol 148 (12) ◽

pp. 5724-5733 ◽

Cited By ~ 69

Author(s):

Sandra M. McLachlan ◽

Yuji Nagayama ◽

Pavel N. Pichurin ◽

Yumiko Mizutori ◽

Chun-Rong Chen ◽

...

Keyword(s):

T Cells ◽

Antibody Response ◽

Hashimoto’S Thyroiditis ◽

Lymphocytic Infiltration ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Graves Disease ◽

Wild Type ◽

Treg Depletion ◽

A Subunit

Hyperthyroidism in Graves’ disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto’s thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies. In some Graves’ patients, thyroiditis becomes sufficiently extensive to cure the hyperthyroidism with resultant hypothyroidism. Factors determining the balance between these two diseases, the commonest organ-specific autoimmune diseases affecting humans, are unknown. Serendipitous findings in transgenic BALB/c mice, with the human TSHR A-subunit targeted to the thyroid, shed light on this relationship. Of three transgenic lines, two expressed high levels and one expressed low intrathyroidal A-subunit levels (Hi- and Lo-transgenics, respectively). Transgenics and wild-type littermates were depleted of T regulatory cells (Treg) using antibodies to CD25 (CD4+ T cells) or CD122 (CD8+ T cells) before TSHR-adenovirus immunization. Regardless of Treg depletion, high-expressor transgenics remained tolerant to A-subunit-adenovirus immunization (no TSHR antibodies and no hyperthyroidism). Tolerance was broken in low-transgenics, although TSHR antibody levels were lower than in wild-type littermates and no mice became hyperthyroid. Treg depletion before immunization did not significantly alter the TSHR antibody response. However, Treg depletion (particularly CD25) induced thyroid lymphocytic infiltrates in Lo-transgenics with transient or permanent hypothyroidism (low T4, elevated TSH). Neither thyroid lymphocytic infiltration nor hypothyroidism developed in similarly treated wild-type littermates. Remarkably, lymphocytic infiltration was associated with intermolecular spreading of the TSHR antibody response to other self thyroid antigens, murine thyroid peroxidase and thyroglobulin. These data suggest a role for Treg in the natural progression of hyperthyroid Graves’ disease to Hashimoto’s thyroiditis and hypothyroidism in humans.

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Altered balance of immunoregulatory T lymphocyte subsets in autoimmune thyroid diseases

Acta Endocrinologica ◽

10.1530/acta.0.1050200 ◽

1984 ◽

Vol 105 (2) ◽

pp. 200-204 ◽

Cited By ~ 10

Author(s):

Takashi Misaki ◽

Junji Konishi ◽

Yasuhiro Iida ◽

Keigo Endo ◽

Kanji Torizuka

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Hashimoto’S Thyroiditis ◽

Mononuclear Cells ◽

Cytotoxic T Cells ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Significant Difference

Abstract. Three monoclonal antibodies recognizing cell surface antigens of total peripheral (OKT3), helper/inducer (OKT4) and suppressor/cytotoxic (OKT8) T lymphocytes were used by an indirect immunofluorescence technique to enumerate peripheral T lymphocytes in 25 patients with Graves' disease (including 4 euthyroid Graves' patients), 16 patients with Hashimoto's thyroiditis and 22 normal controls. Total lymphocyte count and percentages of overall T and helper/inducer T cells among peripheral lymphocytes in these conditions showed no significant difference from those of the controls. Percentage of suppressor/cytotoxic T cells, however, was decreased in Graves' disease patients with or without hyperthyroidism. The ratio of helper/inducer T cells to suppressor/cytotoxic T cells was increased in Graves' disease population and slightly increased in hypothyroid Hashimoto's thyroiditis patients. The ratio correlated with the mitogenic response of peripheral mononuclear cells to phytohaemagglutinin, but not with the serum levels of thyroid hormones nor with the titres of thyroid autoantibodies. These findings are in accordance with the results of previous functional studies and indicate possible defects in suppressor T lymphocytes in autoimmune thyroid disease.

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LncRNA profile in Hashimoto’s thyroiditis and potential function of NONHSAT079547.2

Journal of Molecular Endocrinology ◽

10.1530/jme-19-0239 ◽

2020 ◽

Vol 64 (4) ◽

pp. 259-270

Author(s):

Jingyi Luo ◽

Tingting Liu ◽

Weiping Teng

Keyword(s):

T Cells ◽

Real Time ◽

Potential Function ◽

Real Time Pcr ◽

Hashimoto’S Thyroiditis ◽

Molecular Mechanisms ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Thyroid Peroxidase ◽

Transcriptional Level

Hashimoto’s thyroiditis (HT) is a common organ-specific autoimmune disease, which develops in 0.3–1.5/1000 subjects annually. The aims of this study were to determine the lncRNA profile in peripheral blood CD4+ T cells from HT patients and then to characterize the potential function of NONHSAT079547.2. A total of 37 HT patients and 50 sex- and age-matched healthy controls were enrolled for high-throughput sequencing. Another 43 HT patients and 50 sex- and age-matched controls were enrolled for validation via real-time PCR. Flow cytometry and CCK8 assays were used to measure cell apoptosis and growth levels. Western blotting was used for measuring the expression of growth- and apoptosis-associated proteins. IL-17 serum concentration and transcriptional level in CD4+ T cells of participants were detected by ELISA and real-time PCR, respectively. The mechanism of competitive endogenous RNA was determined using real-time PCR, ELISA, RNA immunoprecipitation, and dual-luciferase assays in Jurkat cells. A total of 7564 significantly differentially expressed lncRNAs were found, of which 3913 lncRNAs were upregulated and 3651 lncRNAs were downregulated in HT group when compared to control group. NONHSAT079547.2 was significantly upregulated in HT patients and was positively correlated with serum thyroid peroxidase antibody level. Further studies confirmed that NONHSAT079547.2 could promote cell growth and control IL-17 expression and secretion via the NONHSAT079547.2/miR-4716-5p/IL-17 axis.This is the first study to describe the lncRNA profile in CD4+ T cells of HT patients. The studies on the function of NONHSAT079547.2 might elucidate the underlying molecular mechanisms and represent potential biomarkers for HT.

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Effects of Prophylactic Thyroid Hormone Replacement in Euthyroid Hashimoto's Thyroiditis

Endocrine Journal ◽

10.1507/endocrj.52.337 ◽

2005 ◽

Vol 52 (3) ◽

pp. 337-343 ◽

Cited By ~ 27

Author(s):

Duygu Yazgan AKSOY ◽

Ulku KERIMOGLU ◽

Hamza OKUR ◽

Hande CANPINAR ◽

Ergun KARAAGAOGLU ◽

...

Keyword(s):

Thyroid Hormone ◽

Hashimoto’S Thyroiditis ◽

Hormone Replacement ◽

Hashimoto's Thyroiditis ◽

Thyroid Hormone Replacement

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Recovery of thyroid function with a decreased titre of antimicrosomal antibody in a hypothyroid man with Hashimoto's thyroiditis

Acta Endocrinologica ◽

10.1530/acta.0.1020531 ◽

1983 ◽

Vol 102 (4) ◽

pp. 531-534 ◽

Cited By ~ 9

Author(s):

Makiko Yamamoto ◽

Kazuro Kaise ◽

Hirofumi Kitaoka ◽

Katsumi Yoshida ◽

Nobuko Kaise ◽

...

Keyword(s):

Hashimoto’S Thyroiditis ◽

Serum Levels ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Normal Range ◽

Surgical Biopsy ◽

Low Levels ◽

Serum Thyroid Hormones ◽

Antimicrosomal Antibody ◽

Serum Tsh

Abstract. A 36 year old man with a diffuse goitre, signs of mild hypothyroidism, strikingly low levels of T4 (0.9 μg/dl) and T3 (24 ng/dl), elevated TSH (140 μU/ml) and elevated microsomal haemagglutination antibody (MCHA, 1:409 600), subsequently became non-goitrous and euthyroid with a decreased titre of antimicrosomal antibody without any medication. At the time of surgical biopsy, serum levels of T4 and T3 had risen to the normal range (4.6 μg/dl and 73 ng/dl, respectively), serum TSH had decreased to 30 μU/ml and the titre of MCHA to 1:25 600. Thyroid specimens showed Hashimoto's thyroiditis. The activity of thyroid peroxidase (TPO) was normal. The latest examination, 1 year and 3 months after initial evaluation, showed that the patient remained euthyroid with no goitre, that serum thyroid hormones were within the normal range (T4 7.7 μg/dl and T3 97 ng/dl), and that TSH was not detectable. The titre of MCHA decreased strikingly to 1:400.

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Relationship Between Thyroid Hormonal Status in Patients with a Hypothyroid Form of Hashimoto’s Thyroiditis and Iodine Concentrations in Drinking Water

Biological Trace Element Research ◽

10.1007/s12011-021-02640-2 ◽

2021 ◽

Author(s):

Olha Kasiyan ◽

Halyna Tkachenko ◽

Natalia Kurhaluk ◽

Svitlana Yurchenko ◽

Alek Manenko

Keyword(s):

Hashimoto’S Thyroiditis ◽

Iodine Concentration ◽

Iodine Intake ◽

Thyroid Stimulating Hormone ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Supply Network ◽

Thyroid Status ◽

Thyroglobulin Antibodies ◽

Regressive Analysis

AbstractThe current study aimed to identify correlative and regressive dependencies between the water iodine concentration and the levels of TSH (thyroid-stimulating hormone), thyroglobulin antibodies (TgAbs), and thyroid peroxidase (TPOAb) in the serum of 168 in patients (34 men and 134 women) with a hypothyroid form of Hashimoto’s thyroiditis who use water from the supply network and individual wells. Based on the water iodine concentration, low and moderate degrees of iodine endemia in the location of the patients were determined. In the groups of men and women using water from different water supply sources, there were direct correlations between the water iodine concentrations and the TgAbs and TPOAb titers as well as an inverse dependence between iodine and TSH levels. Multivariate regressive analysis indicated that TgAb and TSH in the group of women using water from a supply network and TPOAb titers in the group of women using well water were independent factors associated with water iodine concentrations. Statistically significant correlations and regressive dependencies between the water iodine concentrations and the biomarkers of the thyroid status of the patients indicate the risk of Hashimoto’s thyroiditis progression, especially among women with additional iodine intake.

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Salivary gland function in women with Hashimoto’s thyroiditis without xerostomia and the correlation with auto-thyroid antibodies

Nuklearmedizin ◽

10.1055/a-1204-9748 ◽

2020 ◽

Author(s):

Xiao-an Pang ◽

Zhi-xiao Wei ◽

Jun-hong Li ◽

Xiao-qi Pang

Keyword(s):

Salivary Gland ◽

Hashimoto’S Thyroiditis ◽

Thyroid Stimulating Hormone ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Thyroid Peroxidase ◽

Thyroid Autoantibody ◽

Submandibular Glands ◽

Quantitative Parameters ◽

Salivary Function

Abstract Background Hashimoto’s thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function. Methods Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ± 12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ± 12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti– HT, Anti+ HT, Anti– DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. Results None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). Conclusion Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.

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Lithium treatment and thyroid dysfunction – data from an inpatient psychiatric department

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2014 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S545-S545

Author(s):

M. Lázaro ◽

A. Mota ◽

A. Moreira ◽

R. Alves ◽

M.A. Nobre

Keyword(s):

Thyroid Dysfunction ◽

Lithium Treatment ◽

Hormone Replacement ◽

Thyroid Hormone Replacement ◽

High Prevalence ◽

Thyroid Hormone Replacement Therapy ◽

Competing Interest ◽

Psychiatric Department ◽

Term Monitoring

IntroductionLithium is among the most effective therapies for bipolar disorder. Lithium treatment may cause hypothyroidism, goiter or to a lesser extent hyperthyroidism, since it can affect several aspects of thyroid functioning. The prevalence of lithium-associated hypothyroidism varies extensively between studies, reaching up to 47%, and affecting more females than males (5:1).ObjectiveDetermine the prevalence of thyroid dysfunction in an acute inpatient psychiatric department dedicated to affective disorders and its association with lithium therapy.AimsTo review the relation between lithium treatment and thyroid dysfunction.MethodsObservational, descriptive and retrospective study with clinical and laboratorial data concerning all inpatient episodes of 2015 in our Psychiatric Department. A non-systematic literature search was performed in PubMed.ResultsThe present study documented a high prevalence of thyroid dysfunction, particularly in women. Most cases were due to either hypothyroidism or subclinical hypothyroidism. Patients treated with lithium were more often under thyroid hormone replacement therapy (levothyroxine).ConclusionsThe evidence that lithium treatment is associated with hypothyroidism is well established and this condition is easily treatable with levothyroxine. This study highlights the importance of baseline screening of thyroid function and regular long-term monitoring in patients treated with lithium.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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