Autoimmune thyroid disorders in seropositive versus seronegative rheumatoid arthritis

Abstract

Background Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens; they represent a heterogeneous group of disorders that afflict specific target organs or multiple organ systems. Autoimmune thyroid disease (AITD) is a common organ-specific autoimmune disorder affecting mostly middle-aged women. AITD is a term that includes various clinical forms of autoimmune thyroiditis; among these diseases, Hashimoto′s thyroiditis and Graves′ disease are the two most common types and share many features immunologically. Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to severe disability and premature mortality. Given the same pathogenic mechanisms, autoimmune diseases tend to cluster together, and hence this study was designed to investigate the relationship between AITD and RA, particularly seropositive versus seronegative subtypes. Patients and methods The study included 70 patients with evidence of RA. Their diagnosis was based on the 2010 American College of Rheumatology (ACR)-EULAR classification criteria, and they were subclassified into two groups: group I, comprising 35 patients with seropositive RA (positive to one or both seromarkers), and group II, comprising 35 patients with seronegative RA (negative to both seromarkers). Twenty healthy age-matched and sex-matched controls constituted group III. All of the studied participants underwent detailed history-taking and physical examination, focusing on RA duration of illness, clinical features suggestive of thyroid dysfunction, and disease activity score (DAS28). We determined the complete blood count, erythrocyte sedimentation rate, C-reactive protein, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, thyroid stimulating hormone (TSH), serum total T3 (TT3), serum total T4 (TT4), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), anti-thyroid peroxidase (anti-TPO), thyroglobulin Ab, and TSH receptor antibody (TRAb) levels, and also performed a neck ultrasound. Results It was found that erythrocyte sedimentation rate, C-reactive protein, RF, and anti-CCP were significantly higher in RA patients versus controls, particularly in seropositive versus seronegative patients. No significant difference was found between the studied groups as regards TSH, T3, and T4 levels; however, hypothyroidism was found to be more common than hyperthyroidism in RA patients (29 vs. 3% in group I and 9% in group II). Anti-TPO and antithyroglobulin were significantly higher in RA patients versus controls (P < 0.001) and specifically in seropositive (1301.9 ± 1716.0 and 1750.0 ± 1866.2, respectively) versus seronegative patients (799.4 ± 1597.7 and 898.1± 988.11, respectively). TRAbs were detectable in a small subset of RA patients (6% regardless of the serostatus) with significant difference between patients and controls (P = 0.006). Ultrasonographic features of thyroiditis were significantly evident in RA patients versus controls (P = 0.001). A positive correlation was found between RA autoantibodies (RF and anti-CCP) and thyroid autoantibodies (mainly anti-TPO and TRAbs) (P = 0.007, 0.012, 0.004, and 0.035, respectively). Conclusion Thyroid dysfunction and AITD are common in RA patients, with hypothyroidism being the most common disorder, which is prevalent in 29% of patients regardless of their serostatus. This association was independent of disease activity assessed by DAS28. Increased incidence of thyroid autoimmunity was seen in seropositive RA versus seronegative RA patients, as evidenced by higher levels of thyroid autoimmune markers in the former. TRAbs were detectable in a small subset of patients with RA.