title: Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy.
abstract: Thyroid-associated orbitopathy (TAO) rarely occurs in patients with Hashimoto's thyroiditis (HT).
  
  
  
  There is evidence that TSH receptor stimulating antibodies (TSAb) play a role in the pathogenesis of TAO. In this report, the prevalence of TSAb in HT patients with and without TAO was studied.
  
  
  
  This is a longitudinal observational study.
  
  
  
  The study took place in an academic joint thyroid-eye clinic.
  
  
  
  A total of 1055 subjects were included.
  
  
  
  TSAb was measured with a Food and Drug Administration-cleared bioassay that uses Chinese hamster ovary cells expressing a chimeric TSH receptor and a cAMP response element-dependent luciferase. Results of TSAb activity were reported as percentage of specimen-to-reference ratio (SRR%, cutoff >140%).
  
  
  
  We measured the association of TSAb with the risk of TAO in patients with HT.
  
  
  
  Of 700 consecutive and unselected patients with HT, 44 (6%) had overt TAO. Patients with HT+TAO were older (P < .001), heavier smokers (P = .032), and clustered less with autoimmune diseases (P = .005). All healthy controls were TSAb negative. In contrast, serum was TSAb positive in 30/44 (68.2%) and 36/656 (5.5%, P < .001) patients with HT+TAO and HT, respectively. Compared to patients with HT only, serum TSAb levels were higher in HT+TAO (median SRR%, 25th and 75th percentiles): 45, 35-65 vs 192.5, 115-455.3, P < .001. Highest TSAb values were noted in patients with active and severe TAO vs those with mild and inactive TAO: 486, 392-592 vs 142, 73-192.5; P < .001. The odds ratio of TSAb positivity for the risk of TAO adjusted for gender and age was 55.9 (95% confidence interval [CI], 24.6-127, P < .0001), whereas the odds ratio per 10-fold change in TSAb SRR% (quantitative TSAb) was 133 (95% CI, 45-390, P < .0001). The area under the receiver operating characteristic curve for qualitative and quantitative TSAb was 87.2% (95% CI, 80.6-93.8) and 89.4% (95% CI, 84.1-94.7), respectively.
  
  
  
  TSAb is strongly associated with TAO in HT and TSAb may contribute to the pathophysiology of TAO.
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: George J
authors.initials: GJ
authors.lastname: Kahaly
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Diana
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Glang
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kanitz
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Pitz
authors.affiliation: Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Jochem
authors.initials: J
authors.lastname: König
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D049970:Graves Ophthalmopathy / Q000097:blood / Q000276:immunology*; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology*; D055815:Young Adult
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin