Standardization of the radioreceptor assay against anti-thyrotrophin receptor antibodies in Graves' disease

1982 ◽  
Vol 100 (2) ◽  
pp. 245-251 ◽  
Author(s):  
T. W. A. de Bruin ◽  
M. C. Krol ◽  
D. van der Heide
Keyword(s):  
Ammonium Sulphate ◽  
Radioreceptor Assay ◽  
Assay System ◽  
Graves Disease ◽  
Normal Range ◽  
Binding Inhibition ◽  
Order Of Magnitude ◽  
Index Standardization ◽  
Receptor Antibodies ◽  
Pig Serum

Abstract. We studied the possibility of standardizing the radioreceptor assay for the detection of anti-thyrotrophin receptor antibodies, also called thyrotrophinbinding inhibitor immunoglobulins (TBII), to circumvent the problem of inter-assay variability in TBII index calculations. We developed a procedure for conversion of the thyrotrophin-binding inhibition caused by standard amounts (10 mg IgG/ml) of 1.6 m ammonium sulphate precipitates into thyrotrophin-equivalents, i.e. the amount of thyrotrophin required to cause the same thyrotrophin-binding inhibition. We were able to determine a normal range for thyrotrophin-binding inhibition which exhibited little inter-assay variability and was applicable to individual radioreceptor assays. The normal range, expressed in thyrotrophin-equivalents or the logarithm of μU thyrotrophin, was 2.616–3.645, which corresponds to 413–4420 μU. The thyrotrophin-binding inhibition by 1.6 m ammonium sulphate precipitates from sera of 17 untreated patients with Graves' disease was also expressed in thyrotrophin-equivalents. For 15 patients (88%) the thyrotrophin-equivalent values were above the normal range, whereas only 10 patients (59%) had a positive TBII index (using the same sample). This indicated that 5 patients had anti-thyrotrophin receptor antibodies in spite of their negative TBII index. Standardization based on the IgG content of the test samples therefore seems to be imperative. Pig serum 1.6 m ammonium sulphate precipitates, which were tested in a porcine assay system, yielded thyrotrophin-equivalent values that corresponded closely to the normal range for the human assay system, suggesting that the normal range of thyrotrophin-binding inhibition is in the same order of magnitude in porcine and human assay systems.

scholarly journals Blocking Type Anti-TSH Receptor Antibodies Detected by Radioreceptor Assay in Graves' Disease.

2001 ◽  
Vol 48 (6) ◽  
pp. 703-710 ◽  
Author(s):  
HISATO TADA ◽  
YUKIKO IZUMI ◽  
YUKIHIKO WATANABE ◽  
TORU TAKANO ◽  
SHUJI FUKATA ◽  
...  
Keyword(s):  
Radioreceptor Assay ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies ◽  
Blocking Type

Impact of the serum thyroglobulin concentration on the diagnostics of benign and malignant thyroid diseases

2000 ◽  
Vol 39 (05) ◽  
pp. 133-138 ◽  
Author(s):  
W. Dembowski ◽  
H.-J. Schroth ◽  
K. Klinger ◽  
Th. Rink
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Thyroid Volume ◽  
Nodular Goiter ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Normal Range ◽  
Serum Thyroglobulin ◽  
Diffuse Goiter ◽  
Hyperthyroid Patients

Summary Aim of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. Methods: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto’s thyroiditis and 30 hyperthyroid patients with Graves’ disease. Results: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto’s thyroiditis showed slightly decreased Tg levels. In Graves’ disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). Conclusion: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves’ disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

Anti-thyrotrophin receptor antibodies in Graves' disease as demonstrated directly by immunoprecipitation assay

1983 ◽  
Vol 102 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Tjerk W. A de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol
Keyword(s):  
Binding Site ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Immunoprecipitation Assay ◽  
Receptor Complexes ◽  
Auto Antibody ◽  
Receptor Antibodies ◽  
Normal Controls

Abstract. An immunoprecipitation assay was developed to determine the presence of antibodies against human TSH1 receptors. With this assay we were able to demonstrate that in comparison with sera from normal controls, 24 out of 30 (80%) sera from patients with untreated Graves' disease could immunoprecipitate more [125I]TSH-TSH receptor complexes. In 9 assays, an average of 14.1 ± 3.7% (sd) of the [125I]TSH-TSH receptor complexes was immunoprecipitated by the 30 Graves' sera vs 9.8 ± 3.0% by the normal pool serum (n = 23) (P < 0.001) and 7.7 ± 2.8% by the 22 normal sera (P < 0.001). One serum of the 24 positive Graves' sera was studied in detail. The results suggest that this serum contained an anti-TSH receptor auto-antibody directed towards a different determinant on the TSH receptor than the TSH binding site.

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.

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.

Graves’ disease and recurrence in ectopic thyroid tissue after total thyroidectomy

2021 ◽  
Vol 14 (7) ◽  
pp. e243313
Author(s):  
Clara Cunha ◽  
Catia Ferrinho ◽  
Catarina Saraiva ◽  
João Sequeira Duarte
Keyword(s):  
Total Thyroidectomy ◽  
Radioactive Iodine ◽  
Thyroid Tissue ◽  
Neck Mass ◽  
Thyroid Stimulating Hormone ◽  
Ectopic Thyroid ◽  
Treatment Withdrawal ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Levothyroxine Treatment

We report a case of a 46-year-old woman who presented with a midline neck mass 2 years after total thyroidectomy for Graves’ disease. Despite levothyroxine treatment withdrawal, she remained biochemically with subclinical hyperthyroidism. Her thyroid stimulating hormone receptor antibodies were consistently elevated. Neck ultrasonography revealed an infrahyoid solid nodule and pertechnetate scintigraphy confirmed an increased uptake at the same level, without any uptake in the thyroid bed. Treatment with methimazole 5 mg/day was initiated with clinical improvement and achievement of euthyroidism. After that, she received 10 mCi of radioactive iodine. Since then, she experienced regression of the neck mass and is doing well on a replacement dose of levothyroxine. Recurrence of Graves’ disease in ectopic thyroid following total thyroidectomy is extremely rare. This diagnose should be considered in patients who underwent total thyroidectomy and remained with thyrotoxicosis despite decreasing the levothyroxine dose.

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