Evidence for Thyrotropin (TSH)-Blocking Activity in Goitrous Hashimoto’s Thyroiditis with Assays Measuring Inhibition of TSH Receptor Binding and TSH-Stimulated Thyroid Adenosine 3′,5′-Monophosphate Responses/Cell Growth by Immunoglobulins

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Abstract
There are two forms of autoimmune thyroiditis that may cause hypothyroidism: autoimmune atrophic thyroiditis (primary idiopathic hypothyroidism or primary myxedema) and autoimmune goitrous thyroiditis (Hashimoto’s disease). Patients with the former have impalpable thyroid glands, and those with the latter have goiters. We studied TSH binding inhibitory immunoglobulins (TBII), TSH-stimulated cAMP response inhibitory immunoglobulins (TSII), and TSH-stimulated cell growth inhibitory immunoglobulins (TGII) in 42 patients with the former (group 1) and 115 patients with the latter (group 2). Porcine thyroid cells in primary culture and rat thyroid cells in continuous culture (FRTL-5 cells) were used to study TSII and TGII activities, respectively; TSII was expressed as percent inhibition of 0.1 mU/ml TSH-stimulated cAMP response by the patient’s immunoglobulin (IgG; 1 mg/ml) during 2-h incubation, and TGII was expressed as percent inhibition of 10 mU/ml TSH-stimulated [14C]thymidine incorporation by the patient’s IgG (1 mg/ml) during 24-h incubation. The new findings in this report are: 1) some patients in both groups had TBII, TSII, and/ or TGII; 2) the frequency of the presence of TBII, TSII, and TGII in the patients with autoimmune atrophic thyroiditis was higher than that in the patients with autoimmune goitrous thyroiditis, and TSII and TGII were significantly associated with autoimmune atrophic thyroiditis; 3) no correlation was found between goiter size and TBII, TSII, or TGII activity; and 4) there were good correlations between TBII, TSII, and TGII activities. We also found that TSH-stimulated thymidine incorporation was through cAMP production and that the inhibitory IgGs inhibited TSH-stimulated thymidine incorporation by decreasing cAMP production in FRTL-5 cells, but not in porcine or human thyroid cells.