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Thyroid Receptor Autoantibodies
James B. Peter, M.D., Ph.D.
Thyroid-stimulating immunoglobulins (TSI), a variety of thyroid receptor antibodies (TRAb), are identified by their capacity to increase adenyl cyclase activity in the Fisher rat thyroid line (FRTL-5). Elevated TSI are found in over 90% of patients with Graves disease.1 TSI and thyroid growth-promoting immunoglobulin G are probably identical.2 The assay for TSI is more sensitive and specific for Graves disease than is the assay for thyrotropin-binding inhibitory immunoglobulins (TBII),1 which are another type of TRAb typically found in the absence of TSI in hypothyroidism and often in the presence of TSI in Graves disease.3 High levels of TBII may be predictive of recurrent disease.4 Patients who remain positive for TBII after antithyroid drug treatment tend to relapse within six months, but no relation to long-term relapse is found.5 Treatment with thyroxine during antithyroid therapy for Graves disease causes decreases in levels of TBII and decreased frequency of recurrence of hyperthyroidism6 (similar decreases in thyroid antibodies are seen when autoimmune thyroiditis is treated with thyroxine7). TBII is associated with hypothyroidism in Hashimoto thyroiditis and atrophic thyroiditis,8 but the predictive value of TBII for development of hypothyroidism is not established. Elevated levels of TBII and suppressed serum thyroid stimulating hormone (TSH) concentrations in euthyroid relatives of patients with Graves disease are associated with an increased potential for development of hyperthyroidism, but available data suggest that the positive predictive value is too small to be clinically useful.9 HLA-DR3 is not predictive of relapse but the presence of HLA-DR4 is associated with remission and with absence of TBII.5 Monitoring TSI is a good guide for duration of anti-thyroid treatment.10 TBII and TSI are useful during pregnancy for prediction of thyroid dysfunction in infants born of mothers with a history of Graves disease; in infants of mothers who had thyroidectomy for Graves disease and in infants of mothers who have autoimmune thyroiditis.11 Several assays describing eye muscle-reactive antibodies in thyroid-associated ophthalmopathy were recently described, but the sensitivity and specificity are too low to provide worthwhile clinical information.12-14 A recently cloned membrane-bound autoantigen expressed in thyroid and eye muscle is a promising target.15 TSI are occasionally found in patients with concomitant Graves disease and metastatic thyroid carcinoma.16 TSI in the presence or absence of TBII can be detected in the serum of some patients with subclinical Graves disease before the onset of the overt hyperthyroidism.17 TSI and TBII can be detected in 15% and 19%, respectively, of patients with silent thyroiditis; their presence is associated with transient hypothyroidism.18 Thyroid-stimulating activity in sera of normal pregnant women is due at least in part to increased levels of hCG;19 this is not a problem, however, in the usual assay for TSI which uses purified IgG. Cell-based, but not immunoblot-based assays of expressed, recombinant TSH receptor for detection of TRAb are promising.20-22
See Also:
 Thyroid Growth-Promoting Immunoglobulins
| 3250 |
Thyroid Stimulating Hormone, 3rd Generation |
| 3250SR |
Thyroid Stimulating Hormone, 3rd Generation with serial reporting |
| 1091 |
Thyroid Stimulating Immunoglobulins with TSH |
| 1093 |
Thyrotropin Receptor Autoantibody |
| 1090 |
Thyrotropin Receptor Autoantibody with TSH |
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REFERENCES
- Filetti S, Foti D, Costante G, Rapoport B. Recombinant human thyrotropin (TSH) receptor in a radioreceptor assay for the measurement of TSH receptor autoantibodies. J Clin Endocrinol Metab 1991;72:1096-101.
- Zakarija M, Jin S, McKenzie JM. Evidence supporting the identity in Graves' disease of thyroid-stimulating antibody and thyroid growth-promoting immunoglobulin G as assayed in FRTL5 cells. J Clin Invest 1988;81:879-84.
- Worthington J, Byfield PGH, Himsworth RL. Heterogeneity of circulating TSH-receptor antibodies in thyroid disease demonstrated directly by chromatography. Clin Endocrinol 1991;34:147-54.
- Wilson R, McKillop JH, Pearson DWM, Cuthbert GF, Thomson JA. Relapse of Graves' disease after medical therapy: predictive value of thyroidal technetium-99m uptake and serum thyroid stimulating hormone receptor antibody levels. J Nucl Med 1985;26:1024-8.
- de Bruin TWA, Bolk JH, Bussemaker JK, et al. Graves' disease: immunological and immunogenetic indicators of relapse. Br Med J 1988;296:1292-5.
- Hashizume K, Ichikawa K, Sakurai A, et al. Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N Engl J Med 1991;324:947-53.
- Volpe R, Karlsson A, Jansson R, Dahlberg PA. Evidence that antithyroid drugs induce remissions in Graves' disease by modulating thyroid cellular activity. Clin Endocrinol (Oxf) 1986;25:453-62.
- Chiovato L, Vitti P, Santini F, et al. Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 1990;71:40-5.
- Tamai H, Kasagi K, Morita T, et al. Thyroid response, especially to thyrotropin-binding inhibitory immunoglobulins, in euthyroid relatives of patients with Graves' disease: a clinical follow-up. J Clin Endocrinol Metab 1990;71:210-5.
- Edan G, Massart C, Hody B, et al. Optimum duration of antithyroid drug treatment determined by assay of thyroid stimulating antibody in patients with Graves' disease. Br Med J 1989;298:358-61.
- Zakarija M, McKenzie JM, Eidson MS. Transient neonatal hypothyroidism: characterization of maternal antibodies to the thyrotropin receptor. J Clin Endocrinol Metab 1990;70:1239-46.
- Kendall-Taylor P, Atkinson S, Holcombe M. A specific IgG in Graves' ophthalmopathy and its relation to retro-orbital and thyroid autoimmunity. Br Med J 1984;288:1183-6.
- Ahmann A, Baker JR Jr, Weetman AP, Wartofsky L, Nutman TB, Burman KD. Antibodies to porcine eye muscle in patients with Graves' ophthalmopathy: identification of serum immunoglobulins directed against unique determinant by immunoblotting and enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 1987;64:454-60.
- Hiromatsu Y, Fukazawa H, Guinard F, Salvi M, How J, Wall JR. A thyroid cytotoxic antibody that cross-reacts with an eye muscle cell surface antigen may be the cause of thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 1988;67:565-70.
- Dong Q, Ludgate M, Vassart G. Cloning and sequencing of a novel 64-kDa autoantigen recognized by patients with autoimmune thyroid disease. J Clin Endocrinol Metab 1991;72:1375-81.
- Filetti S, Belfiore A, Amir SM, et al. The role of thyroid-stimulating antibodies of Graves' disease in differentiated thyroid cancer. N Engl J Med 1988;318:753-9.
- Kasagi K, Tamai H, Morita T, et al. Role of thyrotripin receptor antibodies in the development of hyperthyroidism: follow-up studies on nine patients with Graves' disease. J Clin Endocrinol Metab 1989;68:1189-94.
- Morita T, Tamai H, Oshima A, et al. The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis. J Clin Endocrinol Metab 1990;71:1051-5.
- Yoshikawa N, Nishikawa M, Horimoto M, et al. Thyroid-stimulating activity in sera of normal pregnant women. J Clin Endocrinol Metab 1989;69:891-5.
- Filetti S, Foti D, Costante G, Rapoport B. Recombinant human thyrotropin (TSH) receptor in a radioreceptor assay for the measurement of TSH receptor autoantibodies. J Clin Endocrinol Metab 1991;72:1096-101.
- Leedman PJ, Harrison PJ, Harrison LC. Immunoblotting for the detection of TSH receptor autoantibodies. J Autoimmun 1991;4:529-42.
- Ludgate M, Perret J, Parmentier M, et al. Use of the recombinant human thyrotropin receptor (TSH-R) expressed in mammalian cell lines to assay TSH-R autoantibodies. Mol Cell Endocrinol 1990;73:R13-8.
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