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 insomeadults 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 onlywhenthe analysis was restricted to those with severe hypothyroidismwasa decreased prevalence of goiter observed. IgG purified fromTSHR 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.