Prevalence and Functional Significance of Thyrotropin Receptor Blocking Antibodies in Children and Adolescents with Chronic Lymphocytic Thyroiditis

Context: TSH receptor (TSHR) blocking antibodies (Abs) inhibit TSH-induced thyroid growth and function in some adults with chronic lymphocytic thyroiditis (CLT), but their role in the pediatric age range is unknown. Objectives: Our objectives were: 1) to determine the prevalence of TSHR blocking Abs in children and adolescents with CLT and 2) assess their functional significance both in vivo and in vitro. Design and Setting: This was a retrospective study in a referral outpatient setting. Patients: Sera from a total of 87 CLT patients and 33 controls were studied. Main Outcome Measures: TSHR Abs were measured by both ELISA and bioassay. Results: Eight of 87 children and adolescents with CLT (9.2%), including one as young as 4 yr of age, had TSHR Abs in serum as measured by ELISA. The prevalence was significantly higher in individuals whose serum TSH concentration was 20 mU/liter or greater within 3 months of study than in less hypothyroid patients (eight of 45 vs. none of 42, P < 0.005). Conversely, TSHR Ab-positive patients were significantly more hypothyroid at diagnosis but only when the analysis was restricted to those with severe hypothyroidism was a decreased prevalence of goiter observed. IgG purified from TSHR Ab sera retained the TSH binding-inhibitory activity and TSHR Ab-positive sera inhibited TSH-induced stimulation of cAMP significantly more than normal. Conclusions: TSHR-blocking Abs contribute significantly to the severity of the hypothyroidism in some children with CLT, but as compared with adults, they appear to play less of a role in determining the presence or absence of a goiter