Inhibition of Thyrotropin-Induced Adenosine 3′5′-Monophosphate Increase by Immunoglobulins from Patients with Primary Myxedema*

Abstract

Immunoglobulin G (IgG) fractions prepared from the serum of 18 patients with primary myxedema, 9 patients with goitrous Hashimoto's thyroiditis, and 14 normal controls were tested for their ability to alter TSH stimulation of cAMP production in cultured human thyroid cells and the binding of TSH to its receptor. When compared with the cAMP increase induced by 0.1 mU/ml bovine TSH in the presence of normal IgG, cAMP accumulation was significantly inhibited (P less than 0.005) by the addition of IgG from patients with primary myxedema. TSH-induced cAMP accumulation was not affected by IgG from patients with goitrous thyroiditis. IgG from patients with primary myxedema also inhibited the cAMP increase induced by thyroid-stimulating immunoglobulins, but not against the increase induced by prostaglandin E1. None of the IgG tested affected the basal level of cAMP. Two potent inhibitory IgG were strongly positive for TSH-binding inhibitor immunoglobulins. Excluding these, no significant correlation was found between the thyroid stimulation-blocking activity and the TSH-binding inhibitory activity. These data suggest the presence of at least two different types of antibodies in primary myxedema which block adenylate cyclase stimulation by TSH and might be responsible for thyroid dysfunction and atrophy.

The Prediction of thyroid Function in Infants Born to Mothers with Chronic Thyroiditis.

“…Thyroid-stimulation blocking antibody (TSBAb): The effects of IgG on both basal and TSHinduced cAMP were studied by modifying a human thyroid stimulator assay with the cultured thyroid adenoma cells or porcine thyroid cells previously described. (Konishi, et al, 1983(Konishi, et al, , 1985. The results were expressed as the percentage inhibition of cAMP increase and were calculated as follows:…”

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).…”

Characteristics of anti-TSH receptor antibodies in two patients who developed spontaneous hypothyroidism after antithyroid drug therapy for hyperthyroid Graves' disease.

“…On the other hand, a blocking type of anti-TSH receptor antibodies, which was detected in the serum of certain patients Received March 24, 1987; accepted for publication May 15, 1987. 269 with primary hypothyroidism, inhibited the activity of TSH in vitro (Endo et al 1978;Matsuura et al 1980;Konishi et al 1983Konishi et al , 1985 and this will explain the cause of hypothyroidism. The present paper deals with hypothyroidism developed after an antithyroid drug therapy for hyperthyroid Graves' disease in two patients.…”