Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation

Ralli, Massimo; Angeletti, Diletta; Fiore, M.; D’Aguanno, Vittorio; Lambìase, Alessandro; Artico, Marco; Vincentiis, Marco de; Greco, Antonio

doi:10.1016/j.autrev.2020.102649

Cited by 327 publications

(301 citation statements)

References 120 publications

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“…In the present study, we were able to confirm that systemic autoimmune/inflammatory disease is mainly associated with hypothyroidism, 20 which is also in line with the theory of autoimmune mosaic by Shoenfeld 21 …”

Section: Discussionsupporting

confidence: 90%

Dysthyroidism in dermato/polymyositis patients: A case‐control study

Watad

Bragazzi

Damiani

et al. 2020

Eur J Clin Investigation

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Background: Dermatomyositis (DM) and polymyositis (PM) are two rare autoimmune disorders occasionally described with dysthyroidism; however, no solid evidence still proves such an association. Aim: To evaluate the prevalence of dysthyroidism among DM/PM patients. Design and setting:A nation-wide case-control study was conducted. Methods: From the Clalit Health Services health records database, we extracted 2085 (DM = 1475 (70.7%), PM = 610 (29.3%)) PM/DM cases and 10 193 sex-age matched controls in the period 2000-2018. Both univariate and multivariate analyses were performed to evaluate the link dysthyroidism and PM/DM. Survival analysis was also performed.Results: The rate of hyperthyroidism was significantly (P = .0097) higher in cases (n = 40, 1.9%) with respect to controls (n = 123, 1.2%). Similarly, the rate of hypothyroidism was significantly (P < .0001) associated with cases (n = 234, 11.2%) when compared to controls (n = 853, 8.4%). At the multivariate logistic regression analysis, both DM (OR 1.31 [95%CI 1.07-1.60], P = .0087) and PM (OR 1.54 [95%CI 1.21-1.95], P = .004) were significantly associated with hypothyroidism, whereas DM (OR 1.70 [95%CI 1.10-2.61], P = .0165) but not PM (OR 1.45 [0.83-2.55], P = .1947) was found to be associated with hyperthyroidism. Subjects with PM and positive for anti-Sjögren's syndrome-related antigen A (SSA) auto-antibody displayed a significant risk of developing hyperthyroidism .74], P = .0480), whereas individuals with DM and positive for antinuclear antibody (ANA) had a higher risk of developing hyperthyroidism (OR 2.65 [95%CI 1.00-7.03], P = .0498). Conclusions: Physicians treating PM/DM patients should consider screening for thyroid dysfunction on a regular basis.

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Section: Discussionsupporting

confidence: 90%

Dysthyroidism in dermato/polymyositis patients: A case‐control study

Watad

Bragazzi

Damiani

et al. 2020

Eur J Clin Investigation

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“…Our results for the first time proved that metformin can significantly decrease TgAb titer and reduce lymphocyte infiltration in thyroid tissue of HT mice, which provides direct evidence for the therapeutic effect of metformin on HT. Notably, TgAb is not the most accurate indicator of HT, because the level of antibodies may change during the disease (Ralli et al, 2020). However, due to strict control of interference factors in our experiment, the HT group and the metformin treatment group were considered in similar stages of disease course.…”

Section: Discussionmentioning

confidence: 99%

Metformin Reverses Hashimoto’s Thyroiditis by Regulating Key Immune Events

Jia

Zhai

et al. 2021

Front. Cell Dev. Biol.

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BackgroundHashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.MethodsThis study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing.FindingsWe found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment.InterpretationThese experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.

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“…HT, widely seen as the common cause of hypothyroidism ( 15 ), is caused by impaired immune tolerance of autoantigens, the destruction of thyroid cells ( 64 , 65 ). The pathogenesis of HT is considered to be a complex autoimmune process.…”

Section: Mechanism Of Icis-related Thyroid Dysfunctionmentioning

confidence: 99%

Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management

et al. 2021

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Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.

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Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation

Cited by 327 publications

References 120 publications

Dysthyroidism in dermato/polymyositis patients: A case‐control study

Dysthyroidism in dermato/polymyositis patients: A case‐control study

Metformin Reverses Hashimoto’s Thyroiditis by Regulating Key Immune Events

Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management

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