Few studies have been performed to investigate autoimmune diseases associated with organ non-specific rheumatological disorders in children, such as juvenile idiopathic arthritis (JIA). The objective in this study was to determine the frequency of autoimmune diseases of the thyroid gland in children with JIA. Eighty patients with JIA and 81 healthy sex- and age-matched controls were enrolled in the study. Serum free T3, free T4, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, and anti-peroxidase antibodies were evaluated. The mean age was 11.5±5.5 years in the patient group and 10.5±4.9 years in the control group. Twenty-seven of the cases were classified as oligoarticular, 26 as polyarticular, 17 as enthesitis-related, 6 as systemic, and 4 as psoriatic arthritis. Autoimmune thyroid disease was found in 4 patients in the JIA group (5%). There were no significant differences between the study and control groups regarding the existence of anti-thyroid antibodies (p=0.17). Girls were more likely to develop autoimmune thyroiditis (3 girls, 1 boy). Autoimmune thyroiditis was more frequent in patients who had a family history of thyroid disease (p=0.02). There was no statistical correlation between rheumatoid factor (RF) and antinuclear antibody (ANA) positivity and autoimmune thyroiditis (p>0.05). We conclude that there is no need for routine screening of serum thyroid function tests and thyroid antibody levels in patients with JIA in the absence of clinical symptoms.

For each patient, demographic data, JIA subgroup, and family history of thyroid diseases up to second-degree relatives were recorded. Rheumatoid factor (RF) and antinuclear antibody (ANA) titers were examined in the JIA group.

Thyroid Function and Autoimmunity Screening

Serum concentrations of free T3, free T4, thyroid stimulating hormone (TSH), and thyroglobulin (TgA) and thyroperoxidase antibodies (TPOA) were determined by chemiluminescence assays (Diagnostic Products Corporation, Los Angeles, CA, USA). Reference values were 0.35-4.9 µIU/L for TSH, 0.8-2.3 ng/dl for fT4 and 2.1-4.4 pg/ml for fT3. TgA values >50 IU/ml and TPOA values >50 IU/ml were considered as positive. Patients with positive autoantibodies were further evaluated with thyroid ultrasonography. Hypothyroidism was defined as low fT3 and/or fT4 with elevated TSH levels; subclinical hypothyroidism was defined as elevated TSH with normal thyroid hormone levels; and thyrotoxicosis was defined as high fT3 and/or fT4 levels accompanying suppressed TSH. Hypothyroid and thyrotoxic patients also had signs and symptoms of thyroid dysfunction, while subclinical hypothyroid and euthyroid groups were clinically symptom-free. Autoimmune thyroiditis was defined as positive TPOA and/or TgA.

Control group: 81 patients (41 male, 40 female, mean age: 10.5±4.9 years) who were admitted to our hospital for non-autoimmune diseases served as control group. None of these patients had the signs and symptoms of thyroid disease or a chronic disease.

The study protocol was approved by the Ethics Committee of Dokuz Eylül University, Faculty of Medicine.

Statistical Analysis

SPSS 10.0 version was used. Results are expressed as mean ± SD. The Mann-Whitney U test was used for non-normally distributed variables whereas Yates chi-square test and Fisher's exact test were used for normally distributed data. P value <0.05 was considered significant.

Table I. Characteristics and Presence of Thyroid Disease in JIA vs Control Group

Anti-thyroid antibodies were detected in 4 of 80 (5%) JIA patients. The onset of JIA was systemic in 1 of them, enthesitis-related in 1, and polyarticular in the remaining 2. None of the 27 cases with oligoarthritis (OA) had anti-thyroid antibodies; 7 were ANA-positive. Four cases with psoriatic arthritis also did not have antibodies.

Table II presents important demographic and laboratory data of the four patients with anti-thyroid antibodies: Girls were more prone to develop autoimmune thyroiditis (3 girls vs 1 boy). The four patients had subclinical hypothyroidism, hypothyroidism, hyperthyroidism and euthyroidism, respectively. In the control group, one patient had a positive TPOA with normal FT3, FT4, and TSH, and one patient had subclinical hypothyroidism without thyroid antibodies. There were no significant differences between the study and control groups regarding the existence of antithyroid antibodies (p=0.17).

Table II. Clinical and Laboratory Data of JIA Patients with Positive Anti-Thyroid Antibodies

Autoimmune thyroiditis was more frequent in patients who had a family history related to thyroid disease (p=0.02).

There was no statistical correlation between RF and ANA positivity and autoimmune thyroiditis (p>0.05).

In the previous studies[3-6], the majority of the patient population was female. However, in our study, 51% of the patients were male. Özdoğan et al.[14] also reported a male predominance among JIA patients in a Turkish population. The rate of male patients was 56% in their 147 patients. The male predominance due to patients with enthesitis-related arthritis (ERA), a subgroup mostly defined in boys, might explain the low frequency of autoimmune thyroiditis in our study. Twenty-two percent of the study population consisted of patients with ERA. None of the mentioned studies included patients with ERA except the study of Harel et al.[3]. Only a minority of 66 patients (3%) had ERA in that study and 75% of the study population was female.

Recently, Harel et al.[3] reported a higher incidence of anti-thyroid antibodies in patients with oligoarticular JIA. All of the patients with positive anti-thyroid antibodies, which composed 39% of the patient population, had OA. Another study by Alpigiani et al.[4], in which 66% of patients were female, demonstrated significantly higher anti-thyroid antibody positivity, particularly in the OA type. The majority of the patients (64%) were OA. The largest series investigating the coexistence of JIA and autoimmune thyroiditis was reported by Stagi et al.[5]. They evaluated 151 patients, of whom 80% were female, and found a higher prevalence of autoimmune thyroiditis as well as subclinical hypothyroidism in OA type. Fifty-eight percent of the patients had OA. In contrast to these studies, none of the patients with OA had autoimmune thyroiditis in this study. The lower incidence of OA (33%) and female ratio than previous reports may contribute to the lower frequency of autoimmune thyroiditis in this study.

In conclusion, this study demonstrated that there was no significant increase in autoimmune thyroiditis in a group of JIA patients, when compared to a sex- and age-matched control group. Despite the statistical insignificance, the presence of four patients with autoimmune thyroiditis should not be underestimated regarding the evaluation of JIA patients for autoimmune thyroid diseases. Screening for anti-thyroid antibodies is recommended in the presence of clinical symptoms and a positive family history. Further studies with a larger group of patients are needed to demonstrate the frequency of autoimmune thyroiditis in JIA.