We studied 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
IgG to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor
immunoglobulin (TBII),
thyroid stimulation blocking antibody (
TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary
myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto's
thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These
antibodies inhibited the receptor binding of 125I-bTSH dose-dependently, and also inhibited dose-dependently not only TSH-stimulated but also Graves'
IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary
myxedema were significantly correlated with both their
TSBAb (r = 0.665; p less than 0.01) and TGBAb (r = 0.618; p less than 0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong
TSBAb (75.1-100%) and TGBAb (57.4-100%) activities. Transient neonatal
hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby's
IgG inhibited TSH-stimulated cAMP increase and 3H-thymidine incorporation. These data suggest that a significant proportion 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 inhibition of TSH-stimulated cAMP generation.