George J Kahaly1, Christian Wüster2, Paul D Olivo3, Tanja Diana1. 1. Department of Medicine I, Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany. 2. Endocrine Laboratory and Practice, Mainz, Germany. 3. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
Abstract
CONTEXT: Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance. OBJECTIVE: To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO). DESIGN: Controlled, follow-up study. SETTING: Academic tertiary referral center for GD + GO. SUBJECTS: Sixty patients with GD, GD + GO, and controls. INTERVENTION: Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab. MAIN OUTCOME MEASURE: Differentiation among GD phenotypes. RESULTS: All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P < 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P < 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO. CONCLUSIONS: TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.
CONTEXT: Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance. OBJECTIVE: To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO). DESIGN: Controlled, follow-up study. SETTING: Academic tertiary referral center for GD + GO. SUBJECTS: Sixty patients with GD, GD + GO, and controls. INTERVENTION: Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab. MAIN OUTCOME MEASURE: Differentiation among GD phenotypes. RESULTS: All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P < 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P < 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO. CONCLUSIONS:TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.
Authors: Tanja Diana; Hans-Peter Holthoff; Julia Fassbender; Christian Wüster; Michael Kanitz; George J Kahaly; Martin Ungerer Journal: Eur Thyroid J Date: 2020-07-23
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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