What Are the Common Characteristics of Pediatric Patients With Antibody Negative Primary Hypothyroidism?

Background: The most common cause of acquired primary hypothyroidism is autoimmune thyroiditis which is typically associated with positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies. However, some children present with primary hypothyroidism and negative antibodies. Whether there are differences between patients with acquired primary hypothyroidism who have positive vs negative anti-thyroid antibodies has not been systematically examined. Aim:To define the characteristics of patients with primary hypothyroidism and negative antibodies. Methods: A retrospective chart review of patients with hypothyroidism seen in the pediatric endocrine clinic at Riley Hospital for Children in Indianapolis, Indiana from August 2016 until December 2019 was performed. Variables examined included age at diagnosis, signs and symptoms at presentation, height, weight, BMI, TSH, FT4, T4, thyroid peroxidase and anti-thyroglobulin antibodies, family history of thyroid disease, physical exam at diagnosis, and associated diseases. Results: Of 173 patients aged 10.6 ± 3.9 years, 128 (74%) had positive antibodies and 44 (26%) had negative antibodies. Of those with positive antibodies, 80 % were female and 20% were male. Of those with negative antibodies, 53% were female and 47% were male. No differences were seen in the incidence of obesity or Down syndrome in patients with positive antibodies compared with those who had negative antibodies. A positive family history of thyroid disease was present in 45% of those with positive antibodies and in 22% of those with negative antibodies, P=0.006 Fifty-eight patients (45%) with positive antibodies reported excessive fatigue and 40 (31%) had a goiter. In contrast, 10 (22.7%) who had negative antibodies reported mild intermittent fatigue, P=0.006 and 7 (15.9 %) had a goiter, P=0.04 The average TSH in the antibody positive group was 129± 230 mcu/ml compared with 48 ± 131 mcu/ml in those with negative antibodies, p=0.04. A trend was also noted for a lower FT4 in those with positive antibodies (0.68±0.37 vs 0.85±0.27, p=0.050) No other differences in baseline characteristics were seen between patients with negative vs positive antibodies. Conclusion: Patients with positive anti-thyroid antibodies had more severe hypothyroidism and were more likely to report extreme fatigue than those with negative antibodies. It is unknown why some children with acquired primary hypothyroidism presumed due to autoimmune thyroid disease have negative antibodies. Long-term follow-up will be needed to determine whether the natural history of thyroid disease in children with primary hypothyroidism is associated with antibody status.