scholarly journals High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease

2019 ◽  
Vol 104 (7) ◽  
pp. 2561-2568 ◽  
Author(s):  
George J Kahaly ◽  
Christian Wüster ◽  
Paul D Olivo ◽  
Tanja Diana
Keyword(s):  
De Novo ◽  
Graves Disease ◽  
Serum Dilution ◽  
Tertiary Referral Center ◽  
Thyrotropin Receptor Antibodies ◽  
High Dilutions ◽  
Graves Orbitopathy ◽  
Serial Serum ◽  
Receptor Antibodies

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.

scholarly journals Prospective Trial of Functional Thyrotropin Receptor Antibodies in Graves Disease

2019 ◽  
Vol 105 (4) ◽  
pp. e1006-e1014 ◽  
Author(s):  
George J Kahaly ◽  
Tanja Diana ◽  
Michael Kanitz ◽  
Lara Frommer ◽  
Paul D Olivo
Keyword(s):  
Predictive Value ◽  
Prospective Trial ◽  
Thyroid Stimulating Hormone ◽  
Luciferase Expression ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Tertiary Referral Center ◽  
Thyrotropin Receptor Antibodies ◽  
Receptor Antibodies

Abstract Context Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD). Objective To evaluate the clinical utility and predictive value of TSAb/TBAb. Design Prospective 2-year trial. Setting Academic tertiary referral center. Patients One hundred consecutive, untreated, hyperthyroid GD patients. Methods TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibition). Main Outcome Measures Response versus nonresponse to a 24-week methimazole (MMI) treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. Results Forty-four patients responded to MMI, of whom 43% had Graves orbitopathy (GO), while 56 were nonresponders (66% with GO; P < 0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibitory immunoglobulins (TBII) differentiated between thyroidal GD-only versus GD + GO (P < 0.001). Furthermore, at baseline, responders demonstrated marked differences in diluted TSAb titers compared with nonresponders (P < 0.001). During treatment, serum TSAb levels decreased markedly in responders (P < 0.001) but increased in nonresponders (P < 0.01). In contrast, TBII strongly decreased in nonresponders (P = 0.002). All nonresponders and/or those who relapsed during 72-week follow-up period were TSAb-positive at week 24. A shift from TSAb to TBAb was noted in 8 patients during treatment and/or follow-up and led to remission. Conclusions Serum TSAb levels mirror severity of GD. Their increase during MMI treatment is a marker for ongoing disease activity. TSAb dilution analysis had additional predictive value.

Prevalence of Thyroid Peroxidase, Thyroglobulin and Thyrotropin Receptor Antibodies in a Long-Term Follow-Up of Juvenile Graves Disease

Autoimmunity ◽  
2000 ◽  
Vol 32 (3) ◽  
pp. 167-172 ◽  
Author(s):  
Lene Lavard ◽  
Hans Perrild ◽  
Bendt Brock Jacobsen ◽  
Mimmi Høier-Madsen ◽  
Giovanna Bendinelli ◽  
...  
Keyword(s):  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Thyrotropin Receptor Antibodies ◽  
Long Term Follow Up ◽  
Receptor Antibodies

scholarly journals Remission Rate of Graves' Disease and the Trend of Changes in Serum TSH Receptor Antibodies in Prolonged Antithyroid Drug Treatment

2020 ◽  
Vol 18 (Suppl) ◽  
Author(s):  
Danilo Villagelin ◽  
Roberto Bernardo Santos ◽  
João Hamilton Romaldini
Keyword(s):  
Drug Treatment ◽  
Remission Rate ◽  
Antithyroid Drug ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Remission Rates ◽  
Thyrotropin Receptor Antibodies ◽  
Antithyroid Drug Treatment ◽  
The Impact ◽  
Receptor Antibodies

Context: Graves’ disease is an autoimmune disease caused by thyrotropin receptor antibodies (TRAb). These antibodies can be measured and used for the diagnosis, prediction of remission, and risk of Graves’ orbitopathy development. There are three treatments for Graves’ disease that have remained unchanged for the last 75 years: Antithyroid drugs, radioiodine, and surgery. Antithyroid drugs are the first treatment option worldwide and are usually used for 12 - 18 months. Recent reports suggest the use of antithyroid drugs for more than 18 months with better outcomes. This review focuses on two aspects of treatment with antithyroid drugs: The impact of using antithyroid drugs for more than 12 - 18 months on remission rates and the trend of TRAb during prolonged antithyroid drug treatment. Evidence Acquisition: A review was performed in Medline on the published work regarding the duration of ATD treatment and remission of Graves' disease and also ATD treatment and TRAb status during the 1990 - 2019 period. Results: Remission rates are variable (30% - 80%), and many clinical and genetic factors serve as predictors. The long-term use of antithyroid drugs appears to increase remission rates. TRAb values usually decline during ATD treatment, but the trend could occur in two ways: Becoming negative or showing a fluctuating pattern. However, approximately 10% of the patients will remain TRAb-positive after five years of treatment with antithyroid drugs. Conclusions: Antithyroid drugs can be used for long periods with an increase in remission rates, and a gradual decrease in TRAb levels, with the disappearance of TRAb in 90% of the patients after 60 months.

scholarly journals Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves' disease

2002 ◽  
pp. 173-177 ◽  
Author(s):  
T Zimmermann-Belsing ◽  
B Nygaard ◽  
AK Rasmussen ◽  
U Feldt-Rasmussen
Keyword(s):  
Antithyroid Drug ◽  
Diagnostic Sensitivity ◽  
Graves Disease ◽  
Diagnostic Specificity ◽  
Predictive Values ◽  
Negative Test ◽  
Recombinant Human Tsh ◽  
Thyrotropin Receptor Antibodies ◽  
Antithyroid Drug Treatment

OBJECTIVE: Antithyroid drug treatment (ATD) is used world-wide in the treatment of thyrotoxicosis in patients with Graves' disease (GD). The main problem is a relapse rate of 30 to 50% within 2 years after the treatment has stopped. The measurement of thyrotropin receptor antibodies (TRAb) in serum has been used to confirm the diagnosis of GD in selected patients with a diagnostic specificity of 70 to 90%. However, in predicting the recurrence of thyrotoxicosis after discontinuing ATD it has been of little value. The aim of this study was to evaluate the ability of TRAb measured by the more sensitive recombinant human TSH receptor method to predict risk of recurrence of GD after discontinuing ATD. MATERIALS, PATIENTS AND METHODS: One hundred and twenty nine patients with newly diagnosed GD were included. Of these, 58 had relapse of hyperthyroidism in a follow-up of at least 11 months (median 18 months, range 11-49) after discontinuing ATD. In 122 Graves' patients TRAb were measured at the time of diagnosis and in all patients when discontinuing ATD by a competitive radioreceptor assay using recombinant human TSH receptors (TRAK human assay). RESULTS: We found an increased diagnostic specificity (99%) compared with the old TRAK porcine assay. The predictive values of a positive and negative test in relation to the prediction of a relapse of GD were found to be only 55% and 62% respectively when using a cut-off level of 1.5 IU/l, and the predictive value of a positive test decreased to 49% and of a negative test to 60% at a lower cut-off limit (1 IU/l). CONCLUSION: Our study confirms that the new TRAK human assay had a superior diagnostic sensitivity in comparison with the old TRAK porcine assay. Despite the higher diagnostic sensitivity of the TRAK human method, we could not find any improvement of predictive values for relapse of hyperthyroidism in the measurement of TRAb at the end of ATD.

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