Rheumatoid arthritis and thyroid dysfunction: A cross-sectional study and a review of the literature

Mahagna, Hussein; Caplan, Alyssa; Watad, Abdulla; Bragazzi, Nicola Luigi; Sharif, Κassem; Tiosano, Shmuel; Mahroum, Naim; Hendel, Hen; Shoenfeld, Yehuda; Comaneshter, Doron; Cohen, Arnon D; Amital, Howard

doi:10.1016/j.berh.2019.01.021

Cited by 26 publications

(58 citation statements)

References 39 publications

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“…Autoimmune thyroid disease is an organ‐specific autoimmune disorder that emerges due to a complex interaction of environmental and genetic factors . It can either manifest as isolated thyroid disorder or in the context of systemic autoimmune diseases such as SLE or RA . Several studies have reported the association of autoimmune thyroid disorders with SSc .…”

Section: Discussionmentioning

confidence: 99%

“…20,21 It can either manifest as isolated thyroid disorder or in the context of systemic autoimmune diseases such as SLE or RA. 14,15 Several studies have reported the association of autoimmune thyroid disorders with SSc. 16,22,23 However, while most reports showed a robust link between hypothyroidism and SSc, an association with hyperthyroidism is yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…Grave's disease and other autoimmune thyroid disorders, such as autoimmune thyroiditis, are mediated by the production and release of autoantibodies directed against thyroid tissue such as gland components, that consequentially induce overproduction of thyroid hormones . A link between hyperthyroidism and other autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been reported . However, there is no established data regarding the link between hyperthyroidism and SSc.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 A link between hyperthyroidism and other autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been reported. 14,15 However, there is no established data regarding the link between hyperthyroidism and SSc.…”

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confidence: 99%

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Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Akuka

Watad

Comaneshter

et al. 2019

Eur J Clin Investigation

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Background A high prevalence of thyroid disorders has been reported in patients with autoimmune diseases. The link between hyperthyroidism and systemic sclerosis (SSc) has been relatively overlooked, and only a few studies utilizing small samples or case reports have been reported so far. Objectives To investigate the association between SSc and hyperthyroidism. Methods We designed a case‐control study utilizing the medical database of the Clalit Health Services. Chi‐square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Results The study included 2,431 SSc patients and 12,710 age‐ and sex‐matched controls. The mean age of the study population was 63.32 ± 18.06 years (median 66 years), and female‐to‐male ratio was 4.5:1. Age (P < .0001, OR 1.03 [95% CI 1.02‐1.04]), female sex (P = .0015, OR 1.86 [95% CI 1.27‐ 2.74]) and diagnosis of SSc (P = .0011, OR 1.81[95% CI 1.27‐2.58]) were all independently associated with hyperthyroidism. Patients with SSc and hyperthyroidism had 1.54‐fold increase of mortality rates during a mean follow‐up of 17 years than SSc patients without hyperthyroidism, even though at the Cox multivariate survival analysis, only age (HR 1.06 [95% CI 1.06‐1.07], P < .0001) and diagnosis of SSc (HR 2.35 [CI 2.06 to 2.69], P < .0001) resulted associated with a higher risk of mortality. Conclusions Hyperthyroidism is highly prevalent among SSc patients and can negatively impact on their survival rates. Therefore, a pre‐emptive screening may be warranted in all SSc patients. Further studies are needed to evaluate whether tight control and optimal treatment for hyperthyroidism may lead to a reduction of all‐cause mortality in patients with SSc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Akuka

Watad

Comaneshter

et al. 2019

Eur J Clin Investigation

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“…1 The prevalence of AITD is increased in patients with rheumatoid arthritis (RA), making AITD one of the most common co-morbid conditions in RA. 2–9 The underlying pathogenic mechanisms of the co-occurrence between AITD and RA are not well understood, but polymorphisms in genes involved in the regulation of T-cell response may play a key role. 1…”

Section: Introductionmentioning

confidence: 99%

Does autoimmune thyroid disease affect rheumatoid arthritis disease activity or response to methotrexate?

et al. 2020

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ObjectiveTo investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate.MethodsA nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish Rheumatology Quality Register year 2006–2016, with linkage to other nationwide registers to identify comorbidity with AITD defined as thyroxine prescription before RA diagnosis, excluding non-autoimmune causes. We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression.ResultsAt diagnosis, patient reported outcome measures (PROMs; patient global, Health Assessment Questionnaire Disability Index and pain) but not objective disease activity measures (erythrocyte sedimentation rate and swollen joint count) were significantly higher (p<0.05 for all PROMs) among RA patients with AITD compared with those without. The level of DAS28 was 5.2 vs 5.1. By contrast, AITD had little influence on EULAR response to methotrexate at 3 months (OR of non/moderate response=0.95, 95% CI 0.8 to 1.1), nor at 6 months. When stratified by age, however, AITD was more common among EULAR non/moderate responders at 3 and 6 months in patients below 45 years resulting in ORs of non/moderate response of 1.44 (0.76–2.76) and 2.75 (1.04–7.28).ConclusionAt diagnosis, RA patients with concomitant AITD score worse on patient reported but not on objective RA disease activity measures, while DAS28 was only marginally elevated. The overall chance of achieving a EULAR good response at 3 or 6 months remains unaffected, although among a limited subgroup of younger patients, AITD may be a predictor for an inferior primary response.

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Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization

Tan,

Yao,

Lin

et al. 2024

Arthritis Care & Research

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ObjectivesRheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co‐occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods.MethodsBi‐directional two‐sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function traits datasets in the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR‐BMA) was performed to adjust for possible competing risk factors. A sensitivity dataset, which included patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions.ResultsA significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD), as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR‐MBA results showed that RA and AITD were independent risk factors in their bi‐directional causality, even in the presence of other competing risk factors (Padj < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them.ConclusionOur results illustrate the significant bi‐directional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in RA patients deserves further attention, and vice versa.

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Rheumatoid arthritis and thyroid dysfunction: A cross-sectional study and a review of the literature

Cited by 26 publications

References 39 publications

Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Does autoimmune thyroid disease affect rheumatoid arthritis disease activity or response to methotrexate?

Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization

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