Autoimmunity in patients with resistance to thyroid hormone

Marla S. Barkoff, Masha Kocherginsky, João Anselmo, Roy E. Weiss, Samuel Refetoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Context: Resistance to thyroid hormone (RTH) is an inherited syndrome most often caused by thyroid hormone receptor β (TRβ) gene mutations. Given that autoimmune thyroid disease (AITD) is prevalent in the general population, its coexistence with RTH has been presumed coincidental. It was recently proposed that chronic TSH stimulation in RTH may induce an autoimmune response, thereby increasing the chance of their coexistence. Objective: The aim was to examine the prevalence of AITD in a large cohort with RTH compared with their unaffected first-degree relatives. Subjects and Methods: Among 130 families, 330 individuals with RTH confirmed by the presence of TRβ gene mutations and 92 unaffected first-degree relatives were tested for thyroglobulin and thyroperoxidase antibodies. The presence of AITD was based on at least one of the two antibodies being positive. Data were analyzed according to genotype, gender, age, and familial association. A large homogeneous family was analyzed separately. Results: Individuals with RTH had an increased likelihood of thyroid autoantibodies (odds ratio = 2.36; P = 0.002). In males, the odds of having AITD were higher in individuals with RTH compared to unaffected first-degree relatives (odds ratio = 2.91; P = 0.042). Although female subjects with RTHhad an odds ratio of 1.95 for having thyroid autoantibodies, the difference was not statistically significant (P = 0.097). Antibody prevalence at different ages was not affected by genotype. Conclusions: Individuals with RTH due to TRβ gene mutations have an increased likelihood of AITD compared to unaffected relatives, but the prevalence of thyroid autoantibodies with advancing age is not affected by genotype. These novel findings demonstrate that the association between RTH and AITD is not coincidental.

Original languageEnglish (US)
Pages (from-to)3189-3193
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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