Predicting the Relapse of Hyperthyroidism in Treated Graves’ Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies

AbstractThe aim of this study was to investigate the potential of the new TSH-receptor antibody (TRAb) assays to predict remission or relapse of hyperthyroidism in patients with Graves’ disease (GD) and Graves’ orbitopathy (GO). TRAbs were measured retrospectively in sera from a cohort of GD patients with GO (n=117; remission n=38 and relapse n=79–Essen GO biobank) with automated binding immunoassays: TRAb Elecsys (Cobas Roche) and TRAb bridge assay (IMMULITE, Siemens), and the TSAb (thyroid stimulating Ab) cell-based bioassay (Thyretain, Quidel Corp.). To identify relapse risk/remission of hyperthyroidism patients were followed up at least 10 months after the end of antithyroid drug therapy (ATD) therapy. ROC plot analysis was performed to calculate cut-off levels of TRAb and TSAb for prediction of relapse and remission of hyperthyroidism. Cut-off serum levels are provided for timepoints around 3, 6, 10, and 15 months after the beginning of ATD. Repeated measurements of TRAb increase the rate of relapses predictions to 60% (Elecsys), 70% (IMMULITE), and 55% (Thyretain). Patients with remission have consistently TRAb levels below the cut off for relapse in repeated measurements. The cell-based bioassay was the most sensitive – and continued to be positive during follow up [at 15 months: 90% vs. 70% (IMMULITE) and 65% (Elecsys)]. Identification of relapsing hyperthyroidism is possible with automated immunoassays and cell-based bioassay especially with serial TRAb measurements during the course of ATD therapy. Patient who need eye surgery may profit from an early decision towards definitive treatment.

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Characteristics of anti-TSH receptor antibodies in two patients who developed spontaneous hypothyroidism after antithyroid drug therapy for hyperthyroid Graves' disease.

The Tohoku Journal of Experimental Medicine ◽

10.1620/tjem.152.269 ◽

1987 ◽

Vol 152 (3) ◽

pp. 269-275

Author(s):

KAZURO KAISE ◽

NOBUKO KAISE ◽

KATZUMI YOSHIDA ◽

YOICHI ITAGAKI ◽

MAKIKO YAMAMOTO ◽

...

Keyword(s):

Drug Therapy ◽

Antithyroid Drug ◽

Tsh Receptor ◽

Graves Disease ◽

Antithyroid Drug Therapy ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies

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Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves’ Disease Study

Journal of Thyroid Research ◽

10.1155/2014/165487 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Peter Laurberg ◽

Birte Nygaard ◽

Stig Andersen ◽

Allan Carlé ◽

Jesper Karmisholt ◽

...

Keyword(s):

Thyroid Gland ◽

Clinical Manifestations ◽

Antithyroid Drug ◽

Thyroid Volume ◽

Serum Levels ◽

Tsh Receptor ◽

Remission Induction ◽

Graves Disease ◽

Positive Correlations ◽

Disease Study

Background. Graves’ disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel.Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves’ disease (hyperthyroidism, goiter, and presence of orbitopathy) at the time of diagnosis of hyperthyroidism.Methods. We describe a cohort of 208 patients with newly diagnosed Graves’ hyperthyroidism. Patients were enrolled in a multiphase study of antithyroid drug therapy of Graves’ hyperthyroidism, entitled “Remission Induction and Sustenance in Graves’ Disease (RISG).” Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy.Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three manifestations of Graves’ disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25–30% had orbitopathy.Conclusions. A positive but rather weak correlation was found between TSH-receptor antibodies in serum and the major clinical manifestation of Graves’ disease. Only half of the patients had an enlarged thyroid gland at the time of diagnosis.

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Blocking-type anti-TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves’ disease

Clinical Endocrinology ◽

10.1046/j.1365-2265.2003.01726.x ◽

2003 ◽

Vol 58 (4) ◽

pp. 403-408 ◽

Cited By ~ 8

Author(s):

Hisato Tada ◽

Ikuko Mizuta ◽

Toru Takano ◽

Ke-ita Tatsumi ◽

Yukiko Izumi ◽

...

Keyword(s):

Drug Therapy ◽

Antithyroid Drug ◽

Tsh Receptor ◽

Graves Disease ◽

Antithyroid Drug Therapy ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies ◽

Blocking Type

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A second course of antithyroid drug therapy is effective in patients with relapsed Graves' disease

Endocrine Abstracts ◽

10.1530/endoabs.59.p205 ◽

2018 ◽

Author(s):

Khyatisha Seejore ◽

Fozia Nawaz ◽

Katherine Kelleher ◽

Julie Kyaw-Tun ◽

Julie Lynch ◽

...

Keyword(s):

Drug Therapy ◽

Antithyroid Drug ◽

Graves Disease ◽

Antithyroid Drug Therapy

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Successful Treatment of Graves Disease in Pregnancy with Lugol's Iodine

Scottish Medical Journal ◽

10.1177/003693300004500107 ◽

2000 ◽

Vol 45 (1) ◽

pp. 20-21 ◽

Cited By ~ 1

Author(s):

A. Jamieson ◽

C.G. Semple

Keyword(s):

Drug Therapy ◽

Successful Treatment ◽

Surgical Intervention ◽

Antithyroid Drug ◽

Primary Treatment ◽

Graves Disease ◽

Lugol’S Iodine ◽

Organic Iodine ◽

Antithyroid Drug Therapy ◽

In Pregnancy

We report a case of Grave's disease in pregnancy complicated by intolerance of standard antithyroid drug therapy. We describe the success of prolonged use of organic iodine as a primary treatment prior to surgical intervention.

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Erratum

Acta Endocrinologica ◽

10.1530/acta.0.1210304 ◽

1989 ◽

Vol 121 (2) ◽

pp. 304

Author(s):

H. Schleusener ◽

J. Schwander ◽

C. Fischer ◽

R. Holle ◽

G. Holl ◽

...

Keyword(s):

Drug Therapy ◽

Relapse Rate ◽

Clinical Course ◽

Antithyroid Drug ◽

Graves Disease ◽

Trh Test ◽

Prospective Multicentre Study ◽

Antithyroid Drug Therapy ◽

Significant Difference ◽

The Individual

Abstract. Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P < 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

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Fine mapping MHC associations in Graves’ disease and its clinical subtypes in Han Chinese

Journal of Medical Genetics ◽

10.1136/jmedgenet-2017-105146 ◽

2018 ◽

Vol 55 (10) ◽

pp. 685-692 ◽

Cited By ~ 9

Author(s):

Xun Chu ◽

Minjun Yang ◽

Zhen-Ju Song ◽

Yan Dong ◽

Chong Li ◽

...

Keyword(s):

Amino Acid ◽

Molecular Mechanisms ◽

Amino Acid Level ◽

Antithyroid Drug ◽

Amino Acid Position ◽

Thyroid Stimulating Hormone ◽

Han Chinese ◽

Graves Disease ◽

Hla Genes ◽

Antithyroid Drug Therapy

BackgroundThe classical human leucocyte antigen (HLA) genes were the most important genetic determinant for Graves’ disease (GD). The aim of the study was to fine map causal variants of the HLA genes.MethodsWe applied imputation with a Pan-Asian HLA reference panel to thoroughly investigate themajor histocompatibility complex (MHC) associations with GD down to the amino acid level of classical HLA genes in 1468 patients with GD and 1490 controls of Han Chinese.ResultsThe strongest finding across the HLA genes was the association with HLA-DPβ1 position 205 (Pomnibus=2.48×10−33). HLA-DPA1*02:02 was the strongest association among the classical HLA alleles, which was in perfect linkage disequilibrium with HLA-DPα1 residue Met11 (OR=1.90, Pbinary=1.76×10−31). Applying stepwise conditional analysis, we identified amino acid position 205 in HLA-DPβ1, position 66 and 99 in HLA-B and position 28 in HLA-DRβ1 explain majority of the MHC association to GD risk. We further evaluated risk of two clinical subtypes of GD, namely persistent thyroid stimulating hormone receptor antibody -positive (pTRAb+) group and ‘non-persistent TRAb positive’ (pTRAb−) group after antithyroid drug therapy. We found that HLA-B residues Lys66-Arg69-Val76 could drive pTRAb− GD risk alone, while HLA-DPβ1 position 205, HLA-B position 69 and 199 and HLA-DRβ1 position 28 drive pTRAb+ GD risk. The risk heterogeneity between pTRAb+ and pTRAb− GD might be driven by HLA-DPα1 Met11.ConclusionsFour amino acid positions could account for the associations of MHC with GD in Han Chinese. These distinct HLA association patterns indicated the two subtypes have distinct molecular mechanisms of pathogenesis.

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