Assays for thyroid growth immunoglobulins and their clinical applications: methods, concepts and misconceptions

Graves’ disease is characterized by thyroid hyperfunction and hyperplasia which lead to thyrotoxicosis and goiter. Hyperthyroidism has been clearly related to the presence in plasma of immunoglobulins which stimulate the TSH receptor via its adenylate cyclase, the thyroid stimulatory immunoglobulins (TSI) (1–4). With regard to growth, several facts have suggested that additional mechanisms may be involved. There is no simple relationship between level of function in Graves’ disease and goiter size; indeed there are cases of hyperthyroidism with little increase in thyroid size and others with slight thyrotoxicosis and large goiters. Moreover, the presence of circulating growth-stimulating factors in euthyroid and hypothyroid patients with goiter has been reported (5–10). On the other hand, depending on the species, several biochemical pathways may be involved in the regulation of thyroid cell proliferation: 1) the TSH-activated adenylate cyclase-cAMP cascade (11–13); 2) the cAMP-independent epidermal growth factor mechanism, probably involving protein tyrosine phosphorylation (11,13); and 3) as in other types of cells, the phosphatidylinositol-Ca2+ cascade (14). It is, therefore, quite conceivable that some factors may activate growth of thyroid cells without influencing the rate of hormone synthesis and secretion. It should be pointed out, however, that in a careful study, Jin et al. (15) have been unable to dissociate the cAMP and the proliferative response to TSI in a rat thyroid cell line (FRTL5). © 1987 by The Endocrine Society.Journal ArticleReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identification of tht thyroid Na+/I- cotransporter as a potential autoantigen in thyroid autoimmune diseases

The thyroid gland is the target of several autoimmune diseases. Specific thyroid proteins have been identified as autoantigens associated with these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In this paper, we report that the serum of a patient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I- uptake of dog thyrocytes in culture, even at a 1:1000-fold dilution, without affecting their 86Rb+ uptake. This blocking activity is rare as 147 sera (from patients positive for antibodies to the thyroid microsomes and the gastric parietal cell antigen, patients with Sjögren's syndrome, patients with a high titre of microsomal antibodies and low or negative for antibodies to thyroperoxidase, and patients with a high titre of microsomal antibodies and frank hypothyroidism) were negative when tested for their ability to inhibit I- uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immunizing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH-induced 125I- uptake of dog thyrocytes without affecting the 86Rb+ uptake of the cells. Immunoglobulins purified from the ascite fluid by affinity chromatography on a protein A cellulose column had the same characteristics. Taken together, the data suggest that thyroidal 125I- uptake can be inhibited by antibodies, that autoantibodies in the patient's serum are most probably responsible for the observed inhibition and therefore that the Na+/I- cotransporter is probably an autoantigen