TSH Receptor Antibody Measurement Research Articles

TSH-receptor Antibodies Determined by the First, Second and Third Generation Assays and Thyroid-stimulating Antibody in Pregnant Patients with Graves' Disease

The measurement of TSH receptor antibody (TRAb) has been recommended to predict the risk of neonatal hyperthyroidism (NH) in pregnant women with Graves' disease (GD). For the first generation TRAb (TRAb1) assay with commercial kit (Brahms, Berlin, Germany; or Cosmic co., Tokyo, Japan) an arbitrary limit of 40 U/l or 50% was suggested to indicate risk when measured late in pregnancy. In order to substitute TRAb1 with the second generation TRAb using porcine TSH receptor (pTRAb2) and human recombinant TSH receptor (hTRAb2) and the third generation TRAb (TRAb3) assay for this purpose, we measured TRAb in these four methods late in pregnancy in a total of 62 pregnant women with Graves' disease. The data showed that no cases with TRAb1 >50% has been missed if the TRAb1 assay was replaced by the pTRAb2, hTRAb2 or TRAb3 assay using their equivalent cut-off value of 70%, 10 IU/l, and 75%, respectively, but that an additional group of women would have been included in the risk group, especially in the TRAb3 assay. Next, the effect of maternal TRAb on thyroid function of offspring was studied in the 47 pregnant women with GD (43 with TRAb1 <50% and 4 with TRAb1 >50% during late pregnancy). In 2 women who gave birth to hyperthyroid children at days 6 and 14 of life, the maternal sera had strongly positive levels of TRAb1 (73.5% and 84.1%), pTRAb2 (84.9% and 91.5%), hTRAb2 (40.68 IU/L and 89.70 IU/L) and TRAb3 (92.1% and 93.5%) late in pregnancy, with one case displaying high positive (1114.3%) thyroid stimulating antibody (TSAb) level and the other case had moderate positive (433%) TSAb level. Of the remaining 45 women, 43 had TRAb1 <50% and the other 2 had TRAb >50% including 1 with low TSAb positive and 1 with positive thyroid stimulating blocking antibody (TSBAb) and negative TSAb; all of them gave birth to euthyroid children. Finally, a serial study regarding TRAb in 23 women with Graves' disease during pregnancy showed that TRAb1, pTRAb2, hTRAb2, TRAb3 value and TSAb level decreased significantly as pregnancy progressed. In conclusion, the present study supported TRAb as a useful marker to predict the risk of NH.

Clinical and Prognostic Value of Anti-thyrotropin Antibodies in Children with Graves’ Disease

The aim of the study was to determine the clinical meaning of TSH receptor antibody (TRAb) measurement in patients with Graves’ disease (GD). We measured the level of total TRAb using the 1 st generation of enzyme multiplied immunoassay and studied thyroid status in 30 children with GD at the onset of disease, every 6 months on antithyroid drug therapy and during 12 months after its discontinuation. We investigated the correlation between the changes of thyroid hormones, thyroid volume and TRAb, so as TRAb level and risk of relapse. Results. At disease onset 87% of children presented with “positive” TRAb values, 13% were considered “ambiguous”. TRAb level normalization was evident in 56% patients in mean 13 ± 5 months of therapy, but 23% demonstrated its elevation in future, mean 1.8 ± 0.2 IU/L. TRAb level and thyroid volume (r s = 0.5, p = 0.01), TRAb and FT4 levels (r s = 0.5, p=0.01) on therapy positively correlated. After discontinuation of medication in 38.9% of patients thyrotoxicosis relapsed (all patients with TRAb &gt; 10 IU/L, 37.5% ofpatients with TRAb 1-10 IU/L, and 14.3% with “negative” values). At the onset of disease Ме TRAb was 12.0 (1.42-38.9) IU/L in relapse group and 6.6 (1.43-25.7) IU/L (р &gt; 0.05) in remission group; at the end of the treatment it became 3.85 (0.64-68.9) IU/L and 0.63 (0.12-6.4) IU/L (р = 0.025) respectively. After therapy discontinuation the relapse group trended to TRAb elevation compared to remission group. “Support” methimazole dose was 0.06 ± 0.04 mg/kg/day in remission group and 0.16 ± 0.04 mg/kg/day (р = 0.003) in relapse group. Conclusion. Measurement of TRAb in children with GD is very useful for prediction of disease progression and therapy results. High TRAb level at the onset of disease and at the end of therapy, absence of normalization on therapy are the risk factors for relapse after therapy discontinuation.

Measurements of TSH receptor antibodies in differential diagnosis

The presence of TSH-receptor antibodies (TRAb) in serum is a key abnormality in Graves' disease (GD). The latest generation of assays detects TRAb in around 95% of unselected patients with newly diagnosed GD. TRAb negative patients have a mild disease and respond well to antithyroid drug therapy. In a low iodine intake area, around 15% of patients diagnosed to have multinodular goitre are TRAb positive patients are more hyperthyroid and have more complications to radioiodine therapy, and they may suffer from GD on top of a multinodular goitre. Around 10% of patients with spontaneous (autoimmune) hypothyroidism are TRAb positive. It is uncommon to find TRAb in serum from healthy individuals. TRAb measurement is useful for diagnosing GD in hyperthyroid patients, and for diagnosing remission during anti-thyroid drug therapy. TRAb status can be used to evaluate risk of relapse after withdrawal of anti-thyroid drug therapy, risk of fetal hyperthyroidism after previous radioiodine or surgical therapy of the mother and risk of neonatal hyperthyroidism when the pregnant woman receives anti-thyroid drugs for GD. It is important to recognize differences in quality between TRAb assays.

TSH Receptor Antibody Measurements and Prediction of Remission in Graves' Disease Patients Treated with Minimum Maintenance Doses of Antithyroid Drugs

Prediction of remission is one of the main problems of antithyroid drug (ATD) therapy for Graves' disease especially in patients who are treated with a minimum maintenance dose of ATD. We evaluated the ability of new sensitive TSH receptor antibody (TRAb) assays to predict remission in Graves' patients using two commercially available kits (TRAb-CT from Cosmic Corporation and TRAb-Dyno from Yamasa Corporation), compared to the original PEG assay. When a euthyroid state was achieved for more than 6 months with methimazole 5 mg/day or propylthiouracil 50 mg/day and thereafter for three months with 5 mg every other day or 50 mg every other day, respectively, we discontinued ATD medication. One year of observation after discontinuation of ATD was completed in 71 patients (60 females, median age 43 years, range 18-71), and TRAb values from these patients were analyzed in relation to prognosis. Twenty-six (37%) of the 71 patients had relapse of thyrotoxicosis and 45 remained euthyroid. The median TRAb levels in the relapse group were significantly higher than those in the remission group (P < 0.05). Relapse occurred in 15/51 patients negative by TRAb-CT, in 11/20 patients positive by TRAb-CT (chi2 = 4.1; P < 0.05), in 11/42 patients negative by TRAb-Dyno and in 15/29 patients positive by TRAb-Dyno (chi2 = 4.8; P < 0.05). By contrast, relapse occurred in 23/64 patients with negative TRAb by PEG assay and in 3/7 patients with PEG assay positive values (n.s.). All patients with TRAb-CT values of 30% inhibition or greater, or TRAb-Dyno values of 3.0 U/L or greater relapsed during the observation period. Thus, measurement of TRAb by the new sensitive assays is useful for prediction of remission in our patients.

Predictive Value of TSH Receptor Antibody Measurement in Graves' Disease is Independent on the TSH Receptor (Human or Porcine) but Depends on the Generation of the Assay Used

Predictive Value of TSH Receptor Antibody Measurement in Graves' Disease is Independent on the TSH Receptor (Human or Porcine) but Depends on the Generation of the Assay Used

TSH Receptor Antibody Measurement in the Diagnosis and Management of Graves' Disease Is Rarely Necessaryb

TSH Receptor Antibody Measurement in the Diagnosis and Management of Graves' Disease Is Rarely Necessaryb

TSH Receptor Antibody Measurement in the Diagnosis and Management of Graves’ Disease Is Rarely Necessaryb

TSH Receptor Antibody Measurement in the Diagnosis and Management of Graves’ Disease Is Rarely Necessary^<i>b</i>

Measurement of TSH Receptor Antibody in Pregnant Women with Graves’ Disease Predicts Thyroid Function of the Newborn

We have attempted to clarify the significance of measurement of TSH receptor antibody (TRAb) in pregnant women with Graves’ disease to predict the development of neonatal Graves’ disease. The subjects were seventeen pregnant women with Graves’ disease and their newborns. Blood was taken from the pregnant women within two weeks before delivery and from the newborns within two weeks after birth. Thyroid function and TRAb of the newborns were followed. The correlation of TRAb between pregnant women and newborns was significant (n=12, r=0.8781, p<0.01). Four neonates developed hyperthyroidism. FT4 was elevated after a week in two neonates whose mothers had taken 6 tablets of PTU and 4 of MMI. Blood TRAbs in the umbilical vein from three neonates with hyperthyroidism were significantly high, 78%, 84% and 79%, and their TRAb levels were high at 2 months. One premature baby developed hyperthyroidism, even though his TRAb at 2 weeks was 36%. TRAb values of more than 70% in pregnant women predict the development of hyperthyroidism in newborns. The period of elevation of FT4 in neonates might be affected by antithyroid therapy to their mothers. SFD babies may develop hyperthyroidism, even if their TRAbs are less than 70%. This study shows the significance of TRAb measurement in pregnant women to predict the outcome of thyroid function in their babies.

The Management of Hyperthyroidism due to Graves' Disease in Europe in 1986: Results of an International Survey

In 1986, a survey on the management of hyperthyroidism due to Graves’ disease was undertaken in Europe. The survey was based on the results of a questionnaire mailed to all clinicians who were members of the ETA. Why was it decided to organize an international survey on Graves’ hyperthyroidism? There were four main reasons for ‘revisiting’ this well-known disease. First, clinical thyroidology is changing rapidly owing to the introduction of new techniques for the diagnosis and follow-up of patients with Graves’ disease (such as assays for the quantification of free hormones, TSH-receptor antibody measurements, 123I scintigraphy). It was therefore decided to assess the impact of these innovations. Second, Graves’ disease is a common endocrine disorder, for which three therapeutic options are available: antithyroid drug therapy, radioiodide administration, and surgery. Each of these treatments has advantages and drawbacks and recently, new recommendations for therapy have been proposed by Hennemann et al. (1986) It was therefore considered important to observe how this disease is treated in Europe. Third, hyperthyroidism due to Graves’ disease is a chronic disorder which results from a rather unusual biological association of pathogenic factors: a partly genetic, auto-immune perturbation which leads to abnormal glandular stimulation and to excessive hormone production, coupled with environmental factors chiefly related to dietary iodine intake. Hence, prediction of disease outcome is a crucial issue for the selection of adequate therapy. One of the goals of the study was to assess if and which predictive indices were used. Finally, it was felt that the responses obtained from such a survey could serve to trigger and orient future research, especially as no equivalent inquiry had ever been performed, with the consequence that no general pattern of the management of hyperthyroidism due to Graves’ disease was available.

Do HLA-DR-typing and measurement of TSH-receptor antibodies help in the prediction of the clinical course of Graves' thyrotoxicosis after antithyroid drug treatment?

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

A receptor assay for the measurement of TSH receptor antibodies in unextracted serum.

A receptor assay for TSH receptor antibodies is described in which unextracted serum, detergent solubilised TSH receptors and 125I-labelled TSH are used. The assay was rapid and reproducible with coefficients of inter-assay variation of 12.3%, 2.1 and 2.6% at mean inhibition of TSH binding values of 11, 53, and 79 respectively. Assay sensitivity could be increased by reducing the volume of receptors used but some increase in the scatter of values obtained with individual normal sera was also observed. Comparison of human and porcine TSH receptor preparations indicated that porcine tissue gave greater sensitivity. Analysis of different groups of patients and normal subjects (n = 21) showed the absence of detectable TSH receptor antibody activity in 16 patients with rheumatoid arthritis, 10 with multinodular goitre and 12 with Hashimoto's disease. However the antibody was readily detectable in 28 out of 28 Graves' patients (treated and untreated) who were hyperthyroid at the time of assay.