George J Kahaly1, Tanja Diana1, Jennifer Glang1, Michael Kanitz1, Susanne Pitz1, Jochem König1. 1. 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.
Abstract
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.
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.
Authors: Tanja Diana; Christian Wüster; Paul D Olivo; Angelica Unterrainer; Jochem König; Michael Kanitz; Artur Bossowski; Brigitte Decallonne; George J Kahaly Journal: Eur Thyroid J Date: 2017-08-08
Authors: G J Kahaly; S Ignjatović; M Sarić Matutinović; T Diana; B Nedeljković Beleslin; J Ćirić; M Žarković Journal: J Endocrinol Invest Date: 2021-07-29 Impact factor: 4.256