Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 5; pp. 1998 - 2004
• Main Authors: Kahaly, George J., Diana, Tanja, Glang, Jennifer, Kanitz, Michael, Pitz, Susanne, König, Jochem
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2016; Copyright by The Endocrine Society
• Subjects: Adolescent; Adult; Animals; Antibodies; Autoimmune diseases; CHO Cells; Cricetinae; Cricetulus; Female; Graves Ophthalmopathy - blood; Graves Ophthalmopathy - immunology; Hashimoto Disease - blood; Hashimoto Disease - immunology; Hashimoto's thyroiditis; Humans; Immunoglobulins, Thyroid-Stimulating - blood; Male; Middle Aged; Receptors, Thyrotropin - immunology; Thyroid; Thyroid gland; Thyroid-stimulating hormone; Thyroiditis; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-1220

Context:Thyroid-associated orbitopathy (TAO) rarely occurs in patients with Hashimoto's thyroiditis (HT).Objective: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.Design:This is a longitudinal observational study.Setting:The study took place in an academic joint thyroid-eye clinic.Subjects:A total of 1055 subjects were included.Methods: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%).Main Outcome Measure:We measured the association of TSAb with the risk of TAO in patients with HT.Results: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.Conclusions:TSAb is strongly associated with TAO in HT and TSAb may contribute to the pathophysiology of TAO.