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 variants of the same disease or different pathogenic entities. Conventional thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytotoxic events induce gland atrophy and thus should be detectable more often in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with autoimmune thyroiditis, using a (51)chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Other thyroid-specific antibodies, like TSH binding-inhibiting antibodies, TSH function-blocking antibodies, thyroglobulin antibodies and thyroid peroxidase antibodies, were determined. Cytotoxic antibody activity was 20.5% (median, range 0-54.5%) in patients with autoimmune thyroiditis and 8.3% (median, range 0-18.4%) in controls (p < 0.0001). Analysis 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). The specific lysis of 30% (median; 95% confidence limit 23.9-32.9) in non-goitrous thyroiditis patients was significantly higher than in goitrous patients (16.9%; 95% confidence limit 13.2-20.4) (p = 0.0006). Prevalence of thyroglobulin and thyroid peroxidase antibodies were equally distributed in both groups, with slightly higher levels of thyroid peroxidase antibodies in goitrous thyroiditis (p < 0.05). Both TSH binding-inhibiting and TSH function-blocking antibodies were rarely positive in either atrophic or goitrous disease. Our study shows for the first time a striking association of thyroid cytotoxic antibodies with the atrophic variant of autoimmune thyroiditis. We suggest that the occurrence of cytotoxic antibodies in the pathogenesis of chronic lymphocytic thyroiditis is the decisive event that favors the development of the atrophic rather than goitrous form of the disease.