THYROID CYTOTOXIC ANTIBODIES IN ATROPHIC AND GOITROUS AUTOIMMUNE-THYROIDITIS

It is unknown whether in chronic lymphocytic thyroiditis the goitrous (Hashimoto's thyroiditis) and atrophic forms (primary myxedema) are va riants of the same disease or different pathogenic entities. Conventio nal thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytoto xic events induce gland atrophy and thus should be detectable more oft en in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with aut oimmune thyroiditis, using a (51)chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Ot her thyroid-specific antibodies, like TSH binding-inhibiting antibodie s, TSH function-blocking antibodies, thyroglobulin antibodies and thyr oid peroxidase antibodies, were determined. Cytotoxic antibody activit y was 20.5% (median, range 0-54.5%) in patients with autoimmune thyroi ditis and 8.3% (median, range 0-18.4%) in controls (p < 0.0001). Analy sis of cytotoxicity regarding thyroid size showed a high incidence of cytotoxic antibodies in atrophic disease (median thyroid volume 6 ml), where cytotoxic antibodies were detectable in 80% versus 39% (X(2) = 9.6; p < 0.0001) in goitrous disease (median thyroid volume 36 ml). Th e specific lysis of 30% (median; 95% confidence limit 23.9-32.9) in no n-goitrous thyroiditis patients was significantly higher than in goitr ous patients (16.9%; 95% confidence limit 13.2-20.4) (p = 0.0006). Pre valence of thyroglobulin and thyroid peroxidase antibodies were equall y distributed in both groups, with slightly higher levels of thyroid p eroxidase antibodies in goitrous thyroiditis (p < 0.05). Both TSH bind ing-inhibiting and TSH function-blocking antibodies were rarely positi ve in either atrophic or goitrous disease. Our study shows for the fir st time a striking association of thyroid cytotoxic antibodies with th e atrophic variant of autoimmune thyroiditis. We suggest that the occu rrence of cytotoxic antibodies in the pathogenesis of chronic lymphocy tic thyroiditis is the decisive event that favors the development of t he atrophic rather than goitrous form of the disease.