One third of the patients referred to our pediatric rheumatology center for a positive ANA without fulfilling diagnosis of CTD with concurrent evaluation of thyroid antibodies and thyroid function were found to have positive thyroid antibodies, ATG and ATPO, indicating autoimmune thyroiditis (or Hashimoto's thyroiditis). This is 7 times more frequent than the prevalence of ATG and ATPO reported in the healthy pediatric population internationally, 1.3 - 3.4% [7–11]. Therefore, our practice of screening for clinically silent autoimmune thyroiditis in ANA positive children is substantiated by the increased proportion of thyroid antibodies in these children, with potential to evolve into hypothyroidism. Older age, female gender, and family history of autoimmune disease, though not statistically significant, should raise a higher suspicion for inspection of these antibodies in the presence of a positive ANA. Although not analyzed in this study due to the retrospective design and lower prevalence of Grave's disease in the pediatric population (0.04%) , anti-TSH receptor antibodies should also be considered, as they are also associated with ANA positivity [5, 6], but are typically identified in patients that already have clinical signs and symptoms of hyperthyroidism.
The frequency of ATG and ATPO detected in the presence of an ANA of unknown cause in adults referred to rheumatologists was reported to be 10 - 16%, which is lower than the frequency we reported here in children [12–14]. Hypothyroidism developed in the majority of these patients, 40 - 60%, within 2 years [12–14]. In children with autoimmune thyroiditis, hypothyroidism eventually developed in 20 - 50% within 5 years [7–11]. Fourteen percent of the 31 thyroid antibody-positive patients in our study developed hypothyroidism requiring therapy within our limited follow-up time (mean of 5 months). The annual incidence of a euthyroid child becoming hypothyroid in the presence of thyroid antibodies, ATG or ATPO, is 2 - 3% . Proper identification of these patients is necessary for early and appropriate management.
In conclusion, we found one-third of non-CTD, ANA-positive children to have positive anti-thyroid antibodies associated with autoimmune thyroiditis, ATG and ATPO. Based on these findings and given the increased cumulative risk of euthyroid autoimmune thyroiditis in children evolving into overt thyroid disease, we recommend routine screening of anti-thyroid antibodies, ATG and ATPO, and thyroid function tests, TSH and FT4, in children with a positive ANA.