Prevalence and functional significance of thyrotropin receptor blocking antibodies in children and adolescents with chronic lymphocytic thyroiditis

J Clin Endocrinol Metab. 2009 Dec;94(12):4742-8. doi: 10.1210/jc.2009-1243. Epub 2009 Oct 22.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Blocking / analysis*
  • Child
  • Child, Preschool
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / biosynthesis
  • Longitudinal Studies
  • Male
  • Receptors, Thyrotropin / antagonists & inhibitors*
  • Receptors, Thyrotropin / immunology*
  • Thyroid Function Tests
  • Thyroid Hormones / blood
  • Thyroiditis, Autoimmune / immunology*
  • Thyrotropin / antagonists & inhibitors

Substances

  • Antibodies, Blocking
  • Immunoglobulin G
  • Receptors, Thyrotropin
  • Thyroid Hormones
  • Thyrotropin