scholarly journals Cellular and molecular basis of thyroid autoimmunity

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Joanna Bogusławska ◽  
Marlena Godlewska ◽  
Ewa Gajda ◽  
Agnieszka Piekiełko-Witkowska
Keyword(s):  
Thyroid Gland ◽  
Thyroid Function ◽  
Cell Damage ◽  
Thyroid Autoimmunity ◽  
Clinical Manifestations ◽  
Thyroid Cell ◽  
Special Focus ◽  
Cellular Mechanisms ◽  
Autoimmune Thyroid ◽  
Thyroid Autoantigens

Autoimmune thyroid disease (AITD) is the most common human autoimmune disease. The two major clinical manifestations of AITD are Graves’ disease and Hashimoto’s thyroiditis (HT). AITD is characterized by lymphocytic infiltration of the thyroid gland, leading either to follicular cell damage, thyroid gland destruction, and development of hypothyroidism (in HT) or thyroid hyperplasia, induced by thyroid antibodies which activate thyrotropin receptor (TSHR) on thyrocytes, leading to hyperthyroidism. The aim of this review is to present up-to-date picture of the molecular and cellular mechanisms that underlie the pathology of AITD. Based on studies involving patients, animal AITD models, and thyroid cell lines, we discuss the key events leading to the loss of immune tolerance to thyroid autoantigens as well as the signaling cascades leading to the destruction of thyroid gland. Special focus is given on the interplay between the environmental and genetic factors, as well as ncRNAs and microbiome contributing to AITD development. In particular, we describe mechanistic models by which SNPs in genes involved in immune regulation and thyroid function, such as CD40, TSHR, FLT3, and PTPN22, underlie AITD predisposition. The clinical significance of novel diagnostic and prognostic biomarkers based on ncRNAs and microbiome composition is also underscored. Finally, we discuss the possible significance of probiotic supplementation on thyroid function in AITD.

scholarly journals Differentiating Recurrent Thyroiditis From Graves’ Disease on a Background of Lithium Use

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A927-A927
Author(s):  
Kasi Subbiah ◽  
Jesse Kumar ◽  
Siva Sivappriyan ◽  
Samantha Anandappa
Keyword(s):  
Thyroid Gland ◽  
Thyroid Function ◽  
Post Partum ◽  
Thyroid Autoimmunity ◽  
Clinical Manifestations ◽  
Tsh Receptor ◽  
Inflammatory Cell Infiltrate ◽  
Graves Disease ◽  
Chronic Inflammatory Cell ◽  
Ultrasound Doppler

Abstract A 26-year-old female presented with severe thyrotoxic symptoms 4 months post-partum following an uncomplicated pregnancy; investigations showed a FT4 39.4 pmol/L (n 12 – 22 pmol/L), FT3 8 pmol/L (n 3.1 – 6.8 pmol/L), FT4:FT3 ratio 4.9, TSH <0.02 mU/L (n 0.27 – 4.2 mU/L), TSH receptor antibody (TRAb) < 0.9 IU/L (n < 0.9 IU/L) with normal blood flow on ultrasound doppler and a low (0.2%) Tc99 uptake isotope scan suggesting thyroiditis. 2 years previously she had an episode of thyroiditis (investigations showed FT4 31.2 pmol/L, FT3 7 pmol/L, FT4:FT3 ratio 4.4, TSH <0.02 mU/L and imaging showed low (0.4%) Tc99 uptake) when on lithium 1gm/day for more than a year to treat bipolar disorder. On recurrence, despite compliant treatment with Propranolol and Prednisolone 30mg once daily, thyroid function deteriorated and 2 months later repeat thyroid function testing showed a FT4 > 100 pmol/L, FT3 30.2 pmol/L, FT4:FT3 ratio 3.3 and TSH < 0.02 mU/L. A repeat Tc99 uptake scan showed increased uptake at 13% and ultrasound showed a very vascular bulky thyroid gland. These investigations were suggestive of either a rebound hyperthyroidism (post-thyroiditis) or Graves’ disease. At this stage, TRAb titers were repeated and were now elevated at 4.5 IU/L therefore carbimazole 40mg daily was started. Due to the severity of symptoms, she underwent urgent thyroidectomy. Histopathology showed features of diffuse hyperplasia of the thyroid gland with variably sized follicles lined by cuboidal epithelial cells and a mild patchy chronic inflammatory cell infiltrate in the stroma. Post thyroidectomy she is stable on L-thyroxine therapy. Points for discussion: 1. Lithium is typically used as a mood stabilizer and as thyroid dysfunction is known to exacerbate mood disturbances it is vital that patients are appropriately screened, monitored and treatment is commenced promptly for thyroid disease. 2. Lithium can increase clinical manifestations of thyroid autoimmunity and may influence thyrotoxicosis either due to thyroiditis or Graves’ disease. Differentiating these etiologies is important from the treatment perspective. 3. FT4:FT3 ratios, TSH receptor antibodies, Tc99 uptake scans and ultrasound doppler of the thyroid will assist in diagnostic accuracy. However, in certain rare circumstances, during the recovery phase of thyroiditis, the Tc99 scan can demonstrate diffusely increased activity, which is representative of a rebound phenomenon thus posing a diagnostic dilemma. 4. Finally, TRAb titers may help differentiate the above, but sometimes may change from undetectable to high suggesting changes in thyroid autoimmunity.

scholarly journals Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

2019 ◽  
Vol 73 (2) ◽  
pp. 67-77
Author(s):  
Tatjana Zaķe ◽  
Sandra Skuja ◽  
Aivars Lejnieks ◽  
Valērija Groma ◽  
Ilze Konrāde
Keyword(s):  
Thyroid Autoimmunity ◽  
Treg Cells ◽  
Thyroid Diseases ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Th17 Lymphocytes ◽  
Immunological Mechanisms ◽  
Thyroid Autoantigens ◽  
The Impact

Abstract Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

Thyroid peroxidase antibodies are common in children with HLA-conferred susceptibility to type 1 diabetes, but are weakly associated with thyroid function

2020 ◽  
Vol 33 (8) ◽  
pp. 1027-1030
Author(s):  
Liisa Saare ◽  
Aleksandr Peet ◽  
Vallo Tillmann
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Function ◽  
Thyroid Autoimmunity ◽  
Risk Groups ◽  
Thyroid Peroxidase ◽  
Cross Sectional ◽  
Autoimmune Thyroid ◽  
Thyroid Peroxidase Antibodies ◽  
Hla Dq

AbstractObjectivesThe need for screening for autoimmune thyroid disease in children who have HLA-conferred susceptibility to type 1 diabetes (T1D), but have not yet been diagnosed with T1D, has not been thoroughly studied. The aim of this study was to describe the prevalence of positive thyroid peroxidase antibodies and its effect on thyroid function in children with genetic susceptibility to T1D as well as to describe the association between thyroid autoimmunity and HLA-DQ genotypes.MethodsCross-sectional study in 223 children (112 boys) aged 7.4–10.5 years with HLA-conferred susceptibility to T1D. TPOAb were measured in all children; thyroglobulin antibodies (TGAb) and thyroid function in TPOAb positive subjects.ResultsGirls had a significantly higher median TPOAb concentration than boys (12 vs 11 kU/L; p=0.001). Positive TPOAb occurred in 13.9% and positive TGAb in 4% of subjects. Only two children had mild changes in thyroid function. There was no association between HLA risk groups and the prevalence of TPOAb.ConclusionsTPOAb are common in children with HLA-conferred susceptibility to T1D, yet are weakly associated with thyroid function, suggesting limited value of thyroid screening in this cohort.

scholarly journals Immune Transcriptome of Cells Infected with Enterovirus Strains Obtained from Cases of Autoimmune Thyroid Disease

2021 ◽  
Vol 9 (4) ◽  
pp. 876
Author(s):  
Anello Marcello Poma ◽  
Sarah Salehi Hammerstad ◽  
Angelo Genoni ◽  
Alessio Basolo ◽  
Knut Dahl-Jorgensen ◽  
...  
Keyword(s):  
Autoimmune Diabetes ◽  
Cell Damage ◽  
Thyroid Autoimmunity ◽  
Thyroid Tissue ◽  
Unknown Origin ◽  
Epithelial Cell Line ◽  
Type I ◽  
Thyroid Cells ◽  
Autoimmune Thyroid ◽  
Immune Related Genes

Background: Hashimoto’s thyroiditis and Graves’ disease are autoimmune thyroid disorders (AITD) of unknown origin. Enterovirus (EV) infection of thyroid cells has been implicated as a possible initiator of cell damage and of organ-specific autoimmunity. We asked whether persistent infection of human epithelial cells with EV strains obtained from thyroid tissue of AITD patients could be associated with transcriptional changes capable of fostering immunopathology. Methods: EV isolates obtained from thyroid tissue of AITD cases were used to infect the AV3 epithelial cell line. AV3 cells incubated with a virus-free medium from thyroid tissue of subjects without evidence of thyroid autoimmunity were used as uninfected controls. Transcripts of immune-related genes were compared in infected vs. uninfected cells. Results: The EV genome and antigens were detected only in the cells exposed to AITD-derived virus isolates, not in control cells. Persistent EV infection, while suppressing transcription of several type I IFN and cytokine determinants, was associated with enhanced transcription of NFKB1/RELA, IFNAR1, JAK1/STAT1, i.e., the determinants that play key immunologic roles. Infection also led to upregulation of the CCL2 chemokine and the IL-18 pro-inflammatory interleukin. Conclusion: As in the case of EV strains obtained from autoimmune diabetes, results show that the EV strains that are present in the thyroid of AITD cases do repress IFN and cytokine pathways. JAK1/STAT1 upregulation supports activation of TLR pathways and aberrant T cell signaling. In the early phases of AITD, our results highlight the potential benefit of interventions aimed at blocking the viral infection and easing the inflammatory response.

scholarly journals MON-468 Hypoechoic Nodule Is Not Always the Bad Guy: Lessons Learned from a Patient with Subacute Painful Thyroiditis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pakaworn Vorasart ◽  
Chutintorn Sriphrapradang
Keyword(s):  
Thyroid Gland ◽  
Thyroid Carcinoma ◽  
Thyroid Function ◽  
Clinical Manifestations ◽  
Cervical Lymphadenopathy ◽  
Thyroid Function Tests ◽  
The Right ◽  
Hypoechoic Nodule ◽  
Painful Thyroiditis

Abstract Introduction: The diagnosis of subacute painful thyroiditis (SAT) is primarily based on clinical manifestations (thyroid tenderness and diffuse goiter). Suppressed TSH, elevated erythrocyte sedimentation rate (ESR) and low thyroid uptake help confirm the diagnosis. Thyroid ultrasonography and fine-needle aspiration biopsy (FNAB) are rarely necessitated. SAT produces a typical sonographic findings of ill-defined heterogeneously hypoechoic areas, which is difficult to differentiate from thyroid carcinoma. We herein report a patient with SAT who was initially diagnosed as malignancy. Case Presentation: A 36-year-old female had pain and swelling at the left thyroid gland for 3 weeks. A left thyroid nodule was diagnosed by her primary care physician. Ultrasonography revealed a poorly defined hypoechoic nodule measuring 2.5x1.1x1.5 cm at the mid pole of the left thyroid gland, for which biopsy was recommended. The nodule showed peripheral vascularity and no calcification. No suspicious cervical lymphadenopathy was detected. Histologic analysis from core biopsy found findings consistency with follicular neoplasm. Thyroid function tests were within normal range. She was treated with ibuprofen as management of thyroid pain and referred for surgery. However, the repeated ultrasonography was performed by endocrinologist in the next 2 weeks and found an interval reduction in size of hypoechoic lesion. FNAB was performed due to the risk of infiltrative malignancies. Cytologic analysis was compatible with SAT. ESR was slightly elevated. Surgery was cancelled and she was treated with ibuprofen. Two weeks later, she reported that the left thyroid pain and swelling had subsided. However, she developed thyroid pain associated with glandular tenderness and swelling of the right thyroid. On sonographic examination, the right lobe, which was previously normal was now similarly affected. Thyroid function showed thyrotoxicosis. The patient was given a further course of beta-blocker, ibuprofen and prednisolone for 2 weeks and recovered well. On follow-up at 2 months, the patient developed biochemical hypothyroidism and received levothyroxine replacement. The lesions in the thyroid gland were not visualized in the 6-month follow-up sonography. Conclusion: The ultrasonographic features of the thyroid during the acute stage of SAT may mimic thyroid carcinoma. Awareness of the sonographic findings and interval changes of SAT lesions may helpful for proper diagnosis and treatment of SAT.

scholarly journals Subacute Thyroiditis After mRNA Vaccine for Covid-19

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A956-A957
Author(s):  
Stephanie Franquemont ◽  
Juan Galvez
Keyword(s):  
Thyroid Function ◽  
Inflammatory Markers ◽  
Subacute Thyroiditis ◽  
Urgent Care ◽  
Common Side Effect ◽  
Thyroid Cell ◽  
Rapid Improvement ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Presenting Symptoms

Abstract Introduction: Subacute thyroiditis is a well-documented clinical condition which typically presents 1-2 weeks after an acute viral illness. Presenting symptoms are classically those of thyrotoxicosis but with associated tenderness in the thyroid. Treatment of acute symptoms is possible and the thyroid function will generally normalize with time. Subacute thyroiditis has rarely been reported after administration of viral vaccinations such as the seasonal flu vaccine. We present a case of subacute thyroiditis which presented after administration of the mRNA COVID-19 vaccine. Case: Patient is a 42yo female with no past medical history. She received the first dose of the Pfizer/BioNTech mRNA vaccine for COVID-19 on 12/22/20. Five days later, the patient complained of sore throat and palpitations. These symptoms progressed and she was evaluated in an urgent care on 12/31/20 where she was found to have tachycardia. Infectious work-up, including PCR for COVID-19, was negative and she was sent home. She took ibuprofen with some improvement of her symptoms. The following day she went to the ED; she was found to have a heart rate in the 130s with sinus tachycardia on EKG. Thyroid function testing was done which revealed TSH <0.01, fT4 4.58, fT3 11.8. Her TPO antibody was <28 and inflammatory markers were elevated including sed rate of 62. The patient was prescribed prednisone 40mg daily and propranolol 20mg as needed for symptoms. She reports rapid improvement of symptoms with prednisone. On 1/21/20, thyroid function showed TSH <0.01, fT4 down to 3.2, tT3 normal at 135. Thyroglobulin was elevated at 140.8 with negative thyroglobulin antibody, TRAb and TSI. Her inflammatory markers had decreased with sed rate of 26 and normal C-reactive protein. She had improved symptoms. Discussion: Cases of subacute thyroiditis are most commonly associated with upper respiratory viruses but cases have been reported with traditional inactivated viral vaccines or live-attenuated vaccines such as those for annual influenza. We present the case of a 42-year-old female who has presented with a classic case of subacute thyroiditis which occurred in the time frame after receiving the Pfizer mRNA vaccine for COVID-19. Research has been ongoing for decades regarding development of mRNA vaccines but the mRNA vaccines for the SARS-CoV-2 virus have been the first to be widely distributed to the general population. Thyroiditis has not been reported as a common side effect but the cross recognition between the coronavirus spike protein targeted with the mRNA vaccine and healthy thyroid cell antigens exists as evidenced by this case. Sources: 1. Prummel M, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150:605-618. Altay FA, Guz G, Altay M. 2. Subacute thyroiditis following seasonal influenza vaccination. Hum Vaccin Immunother. 2016;12(4):1033-1034.

scholarly journals Autoimmune thyroid disease: propagation and progression

2003 ◽  
pp. 1-9 ◽  
Author(s):  
AP Weetman
Keyword(s):  
Immune System ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Large Scale ◽  
Thyroid Autoimmunity ◽  
Hla Class I ◽  
Iodine Intake ◽  
Thyroid Cell ◽  
Endogenous Factors ◽  
Autoimmune Thyroid

Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence.The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

scholarly journals Impact of smoking on thyroid gland: dose-related effect of urinary cotinine levels on thyroid function and thyroid autoimmunity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Su-jin Kim ◽  
Min Joo Kim ◽  
Sang Gab Yoon ◽  
Jun Pyo Myong ◽  
Hyeong Won Yu ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Function ◽  
Thyroid Autoimmunity ◽  
Related Effect ◽  
Urinary Cotinine

scholarly journals Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19

2020 ◽  
Author(s):  
David Tak Wai Lui ◽  
Chi Ho Lee ◽  
Wing Sun Chow ◽  
Alan Chun Hong Lee ◽  
Anthony Raymond Tam ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Autoimmunity ◽  
Prognostic Significance ◽  
Disease Status ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Free Triiodothyronine ◽  
Autoimmune Thyroid ◽  
Reactive Protein

Abstract Objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2–related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers. Methods Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission. Results Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. Conclusion Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.

scholarly journals Clinical and subclinical autoimmune thyroid disorders in systemic sclerosis

2007 ◽  
Vol 156 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Alessandro Antonelli ◽  
Clodoveo Ferri ◽  
Poupak Fallahi ◽  
Massimiliano Cazzato ◽  
Silvia Martina Ferrari ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Thyroid Function ◽  
Thyroid Autoimmunity ◽  
Thyroid Volume ◽  
Thyroid Stimulating Hormone ◽  
Control Group ◽  
Thyroid Disorders ◽  
Free Triiodothyronine ◽  
Autoimmune Thyroid ◽  
Number Of Patients

Objective: Several studies have reported the association of systemic sclerosis (SSc) with thyroid autoimmune disorders, but most of them have neither an appropriate control group nor include a complete thyroid work-up. Design: The aim of our study was to evaluate the prevalence of thyroid disorders in a large number of patients with SSc using a complete clinical evaluation. Methods: Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid-peroxidase (AbTPO) autoantibodies, thyroid ultrasonography and blood flow and fine needle aspiration were performed in 202 SSc patients versus 404 gender- and age-matched controls from the general population, with similar iodine intake, to evaluate the prevalence of clinical and subclinical thyroid disorders. Results: Odds ratio (OR) for female SSc versus controls was: for subclinical hypothyroidism, 3.2 (95% CI) = 1.8–5.7); for clinical hypothyroidism, 14.5 (95% CI = 2.3–90.9); for AbTPO positivity, 2.7 (95% CI = 1.8–4.1); for hypoechoic pattern, 3.2 (95% CI = 2.2–4.7); for thyroid autoimmunity, 3.7 (95% CI = 2.6–5.4); for thyroid volume <6 ml, 1.8 (95% CI = 1.2–2.7). OR for thyroid autoimmunity in male SSc versus controls was 10.8 (95% CI = 2.2–52.4). Mean values of TSH in female SSc, and of AbTPO in female and male SSc were higher (P <0.01) than in controls. We observed three cases of Graves’ disease in female SSc versus zero in controls (P = 0.0140), and two cases of papillary thyroid cancer in SSc patients. Conclusions: Thyroid function, AbTPO and ultrasonography should be tested as part of the clinical profile in SSc patients. Females, subjects with positive AbTPO and hypoechoic and small thyroid should have thyroid function follow-up and appropriate treatment in due course.

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