scholarly journals OR18-03 Functional TSH Receptor Antibodies Are a Biomarker for Graves’ Disease - a Prospective Trial

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
George Jean Kahaly ◽  
Tanja Diana ◽  
Michael Kanitz ◽  
Paul D Olivo
Keyword(s):  
Predictive Value ◽  
Prospective Trial ◽  
Tsh Receptor ◽  
Luciferase Expression ◽  
Graves Disease ◽  
Free T4 ◽  
Baseline Serum ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract Objective We aimed to evaluate the clinical utility and predictive value of stimulatory (TSAb) and blocking (TBAb) TSH receptor antibodies in the management of Graves’ disease (GD). Methods Hundred well-defined, consecutive, unselected, untreated hyperthyroid patients with GD were enrolled in a prospective two-year trial. Methimazole (MMI) was administered for 24 weeks according to baseline serum concentrations of free T3/free T4. Starting dose was 5–30 mg/day. Through a titration regimen, this dose was respectively tapered or increased at each subsequent study visit as the patient became euthyroid or remained hyperthyroid. Goals of therapy were to maintain normal fT4 and TSH levels. MMI therapy was stopped at week 24. The main outcome measure was clinical response versus non-response to a 24-week MMI treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. TSAb was reported as percentage of specimen-to-reference ratio (cut-off SRR% <140). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off >40% inhibition). Results Forty-four patients responded to MMI of whom 43% had Graves’ orbitopathy (GO) while 56 were non-responders (66% with GO, p<0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibiting immunoglobulins (TBII) differentiated between thyroidal GD only versus GD+GO (p<0.001). Further, at baseline responders demonstrated marked differences in diluted TSAb titers compared with non-responders (p<0.001). All patients with a TSAb dilution titer above three did not respond to MMI treatment. In contrast, TBII dilution titers did not differentiate between responders and non-responders to MMI and serum samples became TBII negative already at low dilutions. During treatment, serum TSAb levels decreased markedly in responders (p<0.001) but increased in non-responders (p<0.01). In contrast, TBII strongly decreased in non-responders (p=0.002). All non-responders at week 24 and/or those who relapsed during the 72-week follow-up were TSAb positive at week 24. A shift from TSAb to TBAb was noted in eight patients during treatment and/or follow-up and led to remission. Conclusions Serum TSAb levels are a biomarker for and mirror severity of GD. Their increase during MMI treatment is a marker for on-going disease activity. TSAb dilution analysis had additional predictive value.

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.

TSH normalization and negative anti-TSH receptor antibodies - Predictive value for remission in Graves' disease

2017 ◽  
Author(s):  
Catarina Roque ◽  
Francisco Sousa Santos ◽  
Ricardo Capitao ◽  
Carlos Bello ◽  
Catia Ferrinho ◽  
...  
Keyword(s):  
Predictive Value ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Anti-TSH receptor antibodies in Graves' disease modulate the kinetic behaviour of autologous thyroid TSH receptors. Evidence of the IgG-induced cross-linkage of autologous TSH receptors

1984 ◽  
Vol 105 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Tjerk W. A. de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Graves Disease ◽  
Kinetic Behaviour ◽  
High Affinity ◽  
Cross Linkage ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors. Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.

scholarly journals Graves disease with negative TSH receptor antibodies: a presentation of 5 cases

2020 ◽  
Vol 93 (6) ◽  
pp. 417-419
Author(s):  
Aina Scatti Regàs ◽  
Ricard Pujol Borrell ◽  
Roser Ferrer Costa ◽  
Elsa Puerto Carranza ◽  
María Clemente León
Keyword(s):  
Tsh Receptor ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

TSH-RECEPTOR ANTIBODIES IN MOTHERS WITH GRAVES' DISEASE AND OUTCOME IN THEIR OFFSPRING

The Lancet ◽  
1988 ◽  
Vol 331 (8575-8576) ◽  
pp. 14-17 ◽  
Author(s):  
Nobuo Matsuura ◽  
Kenji Fujieda ◽  
Yasuhiro Iida ◽  
Seiichiro Fujimoto ◽  
Junji Konishi ◽  
...  
Keyword(s):  
Tsh Receptor ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

The clinical course of endocrine ophthalmopathy in patients presenting with Graves' disease depending on the effect of radioiodine therapy

2011 ◽  
Vol 57 (3) ◽  
pp. 17-20
Author(s):  
M S Sheremeta ◽  
N Iu Sviridenko ◽  
I M Belovalova ◽  
P I Garbuzov
Keyword(s):  
Radioiodine Therapy ◽  
Clinical Course ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Endocrine Ophthalmopathy ◽  
Post Radiation ◽  
Group 2 ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies ◽  
Group 1

The primary objective of the present work was to study the clinical course of endocrine ophthalmopathy (EOP) following radioiodine therapy (RIT) of Graves' disease (GD) and depending on its effect (development of post-radiation hypothyroidism). The secondary objective was to determine risk factors of EOP progression after radioiodine therapy. This prospective study included 38 patients (76 eyes) allocated to two groups. The patients of group 1 (n=19/38 eyes) presented with thyrotoxicosis at each visit and continued to use thyrostatic agents; those in group 2 (n=19/38 eyes) had hypothyroidism at its early stages (3 and 6 months) and were given substitution therapy with levothyroxin. The development of post-radiation hypothyroidism was shown to strongly influence the clinical course of EOP. In the patients of group 1, EOP remained active throughout the entire observation period (12 months) in the absence of appreciable variations of its integral severity index. In group 2, the same index decreased significantly, but active forms of EOP could be detected by the time of onset of hypothyroidism (6 months) (p=0.0000). After 12 months, the level of anti-TSH receptor antibodies in the patients of group 1 was significantly higher than in those of group 2 (10.8±8.3 and 2.9±2.0 respectively, p=0.0003). The regression rate of EOP symptoms following radioiodine therapy (RIT) of Graves' disease was a function of the efficacy of thyroid 131I radioablation. It is concluded that persistence of anti-TSH receptor antibodies was responsible for the deterioration of the clinical picture of endocrine ophthalmopathy after radioiodine therapy.

scholarly journals TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study

2008 ◽  
Vol 158 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Peter Laurberg ◽  
Göran Wallin ◽  
Leif Tallstedt ◽  
Mirna Abraham-Nordling ◽  
Göran Lundell ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Radioiodine Therapy ◽  
Randomized Study ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Number Of Patients ◽  
The Common ◽  
Initiation Of Therapy ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

IntroductionAutoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism.ObjectiveTo compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity.MethodsPatients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). l-thyroxine (l-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy.ResultsMedical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy.ConclusionThe majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

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