title: Autoimmunity in patients with resistance to thyroid hormone.
abstract: BACKGROUND
  Resistance to thyroid hormone (RTH) is an inherited syndrome most often caused by thyroid hormone receptor beta (TRbeta) 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.
  
  
  METHODS
  Among 130 families, 330 individuals with RTH confirmed by the presence of TRbeta 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 RTH had 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 TRbeta 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.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Marla S
authors.initials: MS
authors.lastname: Barkoff
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: João
authors.initials: J
authors.lastname: Anselmo
authors.forename: Roy E
authors.initials: RE
authors.lastname: Weiss
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
mesh_terms: D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012044:Regression Analysis; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000276:immunology*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics / Q000276:immunology*; D013963:Thyroid Hormones / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones
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