AN ANALYSIS OF THYROTROPHIN RECEPTOR BINDING AND THYROID STIMULATING ACTIVITIES IN A SERIES OF Graves' SERA

Creagh, F. M.; Teece, Michelle; Williams, Susan E.; Didcote, Suzanne; Perkins, William H.; Hashim, F. A.; Smith, Bernard Rees

doi:10.1111/j.1365-2265.1985.tb01097.x

Cited by 34 publications

(23 citation statements)

References 21 publications

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“…In this study, the baseline correlation between TBIAb and TSAb was not so strong (r = 0.55, Table 1), and the r value was similar to those reported by other investigators (0.47 [13], 0.60 [14], and 0.48 [11]). If these two antibodies were identical, the correlation should be much stronger.…”

Section: Discussionsupporting

confidence: 91%

Differences Between Changes in Serum Thyrotropin-Binding Inhibitory Antibodies and Thyroid-Stimulating Antibodies in the Course of Antithyroid Drug Therapy for Graves' Disease

Yamano¹,

Takamatsu²,

Sakane³

et al. 1999

Thyroid

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There has recently been controversy regarding whether the measurement of thyrotropin-binding inhibitory antibodies (TBIAb) is useful in the management of Graves' disease. Another method of assessing Graves' disease by measuring adenylate cyclase activity in thyroid cells, known as thyroid-stimulating antibodies (TSAb), differs from TBIAb not only in terms of assay but also in immunoglobulin type according to recent studies. In this study, the concentrations of TBIAb and TSAb were compared in serial serum samples collected from 29 patients with Graves' hyperthyroidism during 12 months of antithyroid drug therapy. Before therapy, there was a correlation between TBIAb and TSAb (r = 0.59). The radioactive iodine uptake (RAIU) was not significantly correlated with either TBIAb or TSAb (r = 0.20 and r = 0.29, respectively), and the serum free thyroxine (FT4) concentration was also not significantly correlated with either TBIAb or TSAb (r = 0.06 and r = 0.22, respectively). In patients with Graves' ophthalmopathy, TSAb levels were higher than in patients without ophthalmopathy (1015%+/-851% vs. 456%+/-323%, p<0.01), but the TBIAb levels were not significantly different. After antithyroid treatment, TBIAb did not decrease significantly (from 42.1%+/-20.8% to 20.5%+/-19.5%, p = 0.29). On the other hand, TSAb was significantly decreased after 12 months of treatment (from 649%+/-611% to 294%+/-205%, p< 0.05). These findings indicate that TBIAb and TSAb are not identical, and that TSAb has a closer relationship to thyroid function than TBIAb. In the clinical setting, determination of the serum TSAb level may provide a more accurate index of the thyroid status in Graves' disease patients receiving antithyroid therapy.

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Section: Discussionsupporting

confidence: 91%

Differences Between Changes in Serum Thyrotropin-Binding Inhibitory Antibodies and Thyroid-Stimulating Antibodies in the Course of Antithyroid Drug Therapy for Graves' Disease

Yamano¹,

Takamatsu²,

Sakane³

et al. 1999

Thyroid

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“…The considerable improvements in both types of assay described above have enabled a more objective assessment of the relationship between TSH receptor binding and stimulation of cAMP release by TRAb. In a recent analysis of 110 Graves' patients, Creagh et al (19) were able to demonstrate a highly significant relationship (r = 0.65, P < 0.001) between TSH receptor binding (using detergent-solubilized TSH receptors and receptorpurified 125 I-labeled TSH) and stimulation of cAMP release from isolated thyroid cells. However, there were a few marked discrepancies, in particular 2 sera with high levels of receptor-binding activity but no thyroid-stimulating activity.…”

Section: Comparison Of Results From Bioassays and Receptor Assays mentioning

confidence: 93%

“…The properties of these blocking antibodies will be considered in a separate section, but it is important to emphasize that TRAb with blocking activity are rare in Graves' disease [e.g. 2 out of the 110 patients studied by Creagh et al (19) and Hashim et al (29)]. 108 REES SMITH ET AL.…”

Section: Comparison Of Results From Bioassays and Receptor Assays mentioning

confidence: 97%

“…Thyroid cells from human or porcine tissue can be used as well as the rat thyroid cell line FRTL 5 developed by AmbesiImpiombato and his colleagues (20). Bioassays based on cAMP release from isolated thyroid cells show similar sensitivity and specificity to the receptor assays (19) but are less precise and far more time-consuming and expensive.…”

Section: Jb Bioassaysmentioning

confidence: 99%

“…These have resulted from the use of isolated thyroid cells in culture, particularly measurement of cAMP release into a hypotonic medium (16)(17)(18). Although immunoglobulin concentrates are usually assayed, serum dialyzed against hypotonic medium can be used directly (19). Thyroid cells from human or porcine tissue can be used as well as the rat thyroid cell line FRTL 5 developed by AmbesiImpiombato and his colleagues (20).…”

Section: Jb Bioassaysmentioning

confidence: 99%

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Autoantibodies to the Thyrotropin Receptor

1988

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This review considers recent developments in our understanding of the properties of TRAb, particularly measurement of the antibodies and their sites of action and synthesis. Two new assay methods have allowed considerable improvements in the sensitivity, specificity, precision, and ease of measuring TRAb. In particular: 1) receptor assays based on inhibition of receptor-purified labeled TSH binding to detergent-solubilized TSH receptors and 2) bioassays based on stimulation of cAMP release from monolayer cultures of isolated thyroid cells. Detailed studies with the two assays indicate that TSH receptor antibodies nearly always act as TSH agonists in patients with a history of Graves' hyperthyroidism. Studies in areas of dietary iodine sufficiency suggest that measurement of the antibodies at various stages in the course of treating Graves' disease can be of value in predicting the outcome of therapy. However, in areas of iodine deficiency, difficulties in the ability of patients' thyroid tissue to recover from the effects of antithyroid drugs may prevent the receptor antibodies from causing a relapse of thyrotoxicosis. Consequently, the predictive value of receptor antibody measurements would be expected to be lower in these geographical areas. Although patients with a history of Graves' hyperthyroidism nearly always have TRAb which act as TSH agonists, about 20% of patients with frank hypothyroidism due to autoimmune destruction of the thyroid have TRAb which act as TSH antagonists (blocking antibodies). There is some evidence that these blocking antibodies can cause hypothyroidism particularly in the neonate. With regard to the site of synthesis of TRAb, there is now direct evidence that they are synthesized by thyroid lymphocytes, particularly the lymphocytes in close proximity to thyroid follicular cells. This is consistent with the well established effects of antithyroid treatment (drugs, radioiodine, or surgery) on TRAb levels in addition to their effects on thyroid hormone synthesis. Recent studies using affinity labeling with 125I-labeled TSH have enabled elucidation of the structure of the TSH receptor. TSH receptors in human, porcine, and guinea pig thyroid tissue have a two-chain structure in which the TSH binding site is formed on the outside surface of the cell membrane by a water-soluble A subunit (Mr approximately 50 K). The A subunit is linked by a disulfide bridge and weak noncovalent bonds to the amphiphilic B subunit (Mr approximately 30 K). This subunit, which penetrates the lipid bilayer, probably forms the site for interaction of the receptor with the regulatory subunits of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

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Recent Developments in the in vitro Bioassay of TSH and Thyroid-Stimulating Antibodies

Marshall¹,

Ealey²

1986

Immunology of Endocrine Diseases

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AN ANALYSIS OF THYROTROPHIN RECEPTOR BINDING AND THYROID STIMULATING ACTIVITIES IN A SERIES OF Graves' SERA

Cited by 34 publications

References 21 publications

Differences Between Changes in Serum Thyrotropin-Binding Inhibitory Antibodies and Thyroid-Stimulating Antibodies in the Course of Antithyroid Drug Therapy for Graves' Disease

Differences Between Changes in Serum Thyrotropin-Binding Inhibitory Antibodies and Thyroid-Stimulating Antibodies in the Course of Antithyroid Drug Therapy for Graves' Disease

Autoantibodies to the Thyrotropin Receptor

Recent Developments in the in vitro Bioassay of TSH and Thyroid-Stimulating Antibodies

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