Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: comparison with activities of thyrotropin-binding inhibitor immunoglobulins

Abstract

Abstract. We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H] thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3,0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H] thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P<0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P<0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1–100%) and thyroid growth inhibiting immunoglobulin (57.4–100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.

Thyroid antibodies in children of mothers with auto-immune thyroid disease

“…No speci®c distribution pattern could be established. Thyroid function-blocking antibodies are found in up to 75% of patients with primary myxoedema, the atrophic form of auto-immune thyroiditis, but not in healthy adults or patients with hypertrophic Hashimoto thyroiditis [2,7,16]. Considering this, the percentage of children with increased TBAb is high in our study population.…”

“…Increased TSH receptor antibodies (TRAb) are often associated with Graves disease; their presence is indicative of auto-immune hyperthyroidism. TSH function-blocking antibodies (TBAb) and cytotoxic antibodies (CAb) can be found in all types of auto-immune thyroid disease in all age groups but predominate in the atrophic form of Hashimoto thyroiditis [2,3,7,16].…”

Development of Hypothyroidism with Thyroid Stimulation Blocking Antibody long after Treatment with Antithyroid Drugs in a Patient with Hyperthyroid Graves' Disease: A Case Report.

“…[11,14] in autoimmune thyroid disease, respectively. Tamai et al [3] reported that TSBAb might account for hypothyroidism in approximately one third of cases of Graves' disease previously treated with ATDs, and the remaining two thirds might be due to autoimmune thyroiditis.…”

Clinical Applications of TSH Receptor Antibodies in Thyroid Diseases

“…These blocking antibodies (TSBAbs) compete with TSH for receptor binding and block the biological effects of TSH on thyroid cells, including cAMP production, iodine uptake, and thyroid cell growth (26)(27)(28). They induce transient neonatal hypothyroidism when transferred across the placenta (29,30).…”

“…They induce transient neonatal hypothyroidism when transferred across the placenta (29,30). TSBAb assay quantitates inhibition by autoantibodies of the increase in cAMP production or the iodide uptake in response to a standard concentration of TSH in the FRTL-5 cell (26)(27)(28) or CHO-TSHR cell (31,32).…”