The incidence of serologic evidence of antecedent autoimmune thyroiditis in asymptomatic patients referred to an outpatient rheumatology consultation clinic for a positive antinuclear antibody test.

A common cause of referral to outpatient rheumatology clinics at our institution is the presence of a low titer positive antibody test (ANA) in the absence of other symptoms and signs of connective tissue disease. In 1961, White et al., reported on the presence of “antinuclear factor” in 5 out of the 40 patients with “lymphadenoid goiter” (Hashimotoʼs thyroiditis) and thus established the relationship between Hashimoto thyroiditis and antinuclear antibodies (1). The purpose of the present study is to determine what percentage of patients referred to our outpatient rheumatology clinic with a positive ANA have laboratory evidence of prior autoimmune thyroiditis. The study involved 17 patients from our rheumatology consult clinics at the University of New Mexico Health Sciences Center (UNMHSC). Our study was approved by the Human Research Review Committee of the UNMHSC in March 2002. Informed consent was obtained for all study patients. Seventeen patients were identified from our outpatient rheumatology consult clinic who were referred because of a positive ANA test and were screened for the absence of any connective tissue disease. These patients were subsequently tested for thyroid function by a TSH test and evidence of antecedent autoimmune thyroiditis by the measurement of anti-thyroglobulin and anti-peroxidase antibodies. Anti-thyroglobulin (anti-thryrog) and antiperoxidase (anti-tpo) antibody titers were determined using enzyme linked immunosorbent assay. ANA was determined by indirect immunofluorescence using HEp-2 cells as substrate and defined as positive when detected at a serum dilution of more then 1:40 (2, 3). The average age of the patients in our study was 51 years. The group consisted of 15 females and 2 males. The average ANA titer was 1:155 with a range of 1:40 to 1:640, 8 of 17 (47%) had a titer ≥ 1:160. The most common pattern in our study was homogenous which occurred in 14 out of 17 patients Speckled was the next most common with 3 out of 17 patients showing this pattern either alone or in combinations with a homogenous pattern. Lastly, a centromere pattern was noted in 1 of the 17 patients. The overlap between endocrine disorders and the autoimmune rheumatic diseases has been well studied. This is particularly true with respect to autoimmune thyroid disease. An increased prevalence of autoimmune thyroiditis has been found in patients with rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögrenʼs syndrome, giant cell arteritis, and possibly even in patients with eosinophillic fascittis (4). This association is interesting, as it implies in overlap between systemic autoimmune disease (thought to be secondary to a breakdown in peripheral tolerance) and organ specific autoimmune diseases (thought to be secondary to a loss of central tolerance). White et al. reported on the presence of “antinuclear factor” in 5 out of the 40 patients with “lymphadenoid goiter” (i.e. Hashimotoʼs thyroiditis) (1). Thus, the relationship between autoimmune thyroiditis and antinuclear antibodies has long been known. In one study, which involved 168 patients with autoimmune thyroiditis, ANA positivity was found in 58 (35%) of patients. However, many of these same patients were also found to have anti-Ro antibodies, anti-La antibodies, anti-dsDNA antibodies, as well as anticardiolipin antibodies and leukopenia (5). Thus, it is likely that significant portions of these patients in this study had systemic lupus had erythematosus as a cause of positive ANA testing in addition to autoimmune thyroiditis. This overlap can be identified in similar studies as well (6-12). The purpose of our study was to determine what percentage of asymptomatic patients with a positive ANA test had laboratory evidence of prior autoimmune thyroiditis (i.e. Hashimotoʼs thyroiditis). The results of our study indicate that patients referred to our clinics for a positive ANA have a high incidence of serologic evidence of antecedent thyroiditis (3). In the study by Tektonidou et al., which involved 168 patients with autoimmune thyroiditis, in which 58 (35%) were found to have a positive ANA compared with 9% of healthy controls (5). This is also significantly higher than Inamoʼs study, which involved 12 children with Hashimotoʼs thyroiditis. (11) In this study, a positive ANA was found in 4 out of the 12 patients or 33%. The goal of this study was not to ascertain the overall incidence of a positive ANA test in patients with serologic evidence of antecedent thyroiditis, but rather to determine the incidence of serologic evidence for antecedent thyroiditis in patients referred for a positive ANA test. These patients did not meet any criteria for a collagen vascular disease which one would associate with a positive ANA. Thus, the overall incidence of a positive ANA in the total population with antecedent thyroiditis is probably lower and may be in the range of the studies referred to above. We conclude that rheumatologists should be alert to the possibility of antecedent autoimmune thyroiditis as an explanation for a positive antinuclear antibody test in asymptomatic patients in a rheumatology clinic. Furthermore, the high incidence of a low titer ANA in this population represents an important link between an organ specific autoimmune disease, autoimmune thyroiditis, and autoimmune disease of a more systemic nature, such as systemic lupus erythematosus.