Thyrotrophin-blocking antibodies in goitrous primary hypothyroidism: detection by a highly sensitive bioassay and determination of site of action.
Using a highly sensitive bioassay technique, the presence of antibodies capable of blocking the stimulation of thyrocyte function by TSH has been investigated in the sera of a group of 50 patients with primary hypothyroidism. TSH-blocking activity was detected in immunoglobulin (IgG) preparations from the sera of 13 patients (26%). All 13 IgG preparations blocked both TSH-stimulated iodide uptake and cyclic AMP generation (Spearman's rank correlation = 0.6, p = 0.02). However, only one IgG preparation blocked dibutyryl cyclic AMP-stimulated iodide uptake. The presence of TSH-blocking antibody activity was associated with goitrous (ten out of thirteen patients) as well as atrophic (two out of thirteen patients) primary hypothyroidism. Furthermore, TSH-blocking activity was not associated with other thyroid autoantibodies, as thyrotrophin-binding-inhibiting immunoglobulins and anti-TSH antibodies were undetectable in all cases and there was no correlation between TSH-blocking activity and the presence or titre of anti-thyroglobulin or anti-microsomal antibodies. This study indicates that TSH-blocking antibodies are present in the serum of some patients with primary hypothyroidism and are directed towards a site, presumably adjacent to or contiguous with the TSH receptor, that is not the binding site for TSH. The coexistence of TSH-blocking activity and goitre in the majority of these patients implies that these antibodies, although capable of blocking TSH-stimulated thyroid hormone biosynthesis, do not necessarily inhibit the mitogenic action of TSH in vivo.
D000906:Antibodies / Q000032:analysis*; D001666:Binding Sites, Antibody; D005260:Female; D006042:Goiter / Q000276:immunology*; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology*; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D013972:Thyrotropin / Q000276:immunology*
D000906:Antibodies; D013972:Thyrotropin