Thyroglobulin Autoantibodies arise before Thyroperoxidase Autoantibodies in Juvenile Autoimmune Thyroiditis

Thyroglobulin Autoantibodies arise before Thyroperoxidase Autoantibodies in Juvenile Autoimmune Thyroiditis Valentina Verdiani, Debora Ricci, Paolo Piaggi, Michele Marinò, Teresa Rago, Paolo Vitti, Francesco Latrofa Department of Clinical and Experimental Medicine, University of Pisa; Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health, Phoenix, AZ Context. Juvenile Autoimmune Thyroiditis (JAT) is characterized by positive thyroid autoantibodies (thyroglobulin autoantibodies –TgAb and thyroperoxidase autoantibodies –TPOAb), hypoecogenic pattern at thyroid thyroid ultrasound (US) and above-normal TSH levels. Aim of the study was the clinical characterization of JAT, to identify which clinical manifestation appears first. Design. We investigated ≤14 yr-old subjects who had undergone measurement of thyroglobulin autoantibodies (TgAb) and/or thyroperoxidase autoantibodies (TPOAb) in the period 2003-2013 because of a suspected JAT. The subjects with normal laboratory and US findings as well as patients with non-autoimmune thyroid disease associated with positive TgAb and/or TPOAb and patients with Graves’ disease were excluded. The remaining 205 subjects (M = 81, F = 124; age= 8.4 ± 3.3 yrs) showed one or more thyroid abnormal features (positive TgAb, positive TPOAb, hypoecogenic pattern at thyroid US, above-normal TSH level). Results. 54.6% of subjects showed negative TgAb and TPOAb, 30.7% positive TgAb and TPOAb, 12.7% positive TgAb and negative TPOAb and 2.0% positive TPOAb and negative TgAb. A hypoechogenic pattern at thyroid US was observed in 53.3% of juveniles and a previous or current above-normal TSH level in 53.2% of them. Both positive TgAb and positive TPOAb correlated with the hypoechogenic pattern (p = 0.024 and p <0.001 respectively). About 50% of the juveniles with positive TgAb, about 50% of those with positive TPOAb and about 50% of those with hypoechogenic pattern had abnormal TSH levels; none of them correlated with an above-normal TSH levels more than the others. About 70% of ≤4 yr-old juveniles showed high TSH levels in the absence of other thyroid abnormalities (“isolated hyperthyrotropinemia"). Positive thyroid autoantibodies were first observed in the group of 4-6 yr-old juveniles and were confirmed at later ages. The percentage of positive TgAb was higher compared to positive TPOAb for all age groups, although the differences lowered with age. The hypoecogenic pattern was observed in a few 2-4 yr old juveniles and was more frequent (up to 60%) in the older groups. The age distribution was different for positive TgAb (p <0.001), positive TPOAb (p <0.001), hypoechogenic pattern (p <0.001) and above-normal TSH levels (p = 0.003). Conclusions. 1) JAT is extremely rare in < 4 yr-old juveniles; at this age and above-normal TSH level identifies the "isolated hyperthyrotropinemia"; 2) in JAT the appearance of TgAb precede that of TPOAb, pointing to the value of TgAb measurement in the diagnostic work-up of JAT and suggesting that the response to Tg is the prime event of B-cell response in JAT; 3) the value of ultrasonography for the diagnosis of JAT remains unclear