EXCESS IODINE INDUCES THE EXPRESSION OF THYROID SOLID CELL NESTS IN LYMPHOCYTIC THYROIDITIS-PRONE BB W RATS/

Previous epidemiological studies have suggested that lymphocytic thyro iditis and/or an increased iodine intake may be risk factors for the d evelopment of thyroid cancer. We previously reported that excess iodin e accelerated the development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat model. We also found that excess iodine in creased thyroid cell proliferation in a disordered manner. The present study was designed to further explore these observations and to addre ss the question as to whether excess iodine under certain conditions p redisposes the thyroid gland to neoplasia. To test this hypothesis, th e lymphocytic thyroiditis-prone BB/W rat was exposed to excess iodine in drinking water. Ten BB/W rats at 4 weeks of age were given iodine w ater (NaI 0.05%) for 10 weeks, whilst another 10 BB/W rats were given tap water and served as controls. Eighteen normal Wistar rats were als o divided into excess iodine and control groups, served as a compariso n to the BB/W rats. We found that an excess iodine intake accelerated the development of LI in the BB/W rat. Severe LI was usually accompani ed by prominent thyroid cell proliferation, evident as numerous microf ollicles and cell masses, not forming normal thyroid follicles. Numero us lymphocytes and plasma cells often encroached on these areas of inc reased cellular proliferation. The surprising feature, and a possible indicator of activated thyroid cell proliferation, was the high incide nce of thyroid solid cell nest-like lesions (SCN) in the iodine treate d BB/W rats. Two main types of SCN were identified in the BB/W rat thy roid; the first was the solid epidermoid or squamous cell variant and the second type was cystic in structure and was lined by epithelial ce lls, with eosinophilic material or desquamated cells filling the centr e. The incidence of SCN was markedly higher in the excess iodine group (70%) than that in the control group (10%). Thyroid SCN in iodine tre ated rats were generally much larger and more cystic compared with tho se seen in the rat with normal iodine status. SCN were more often pres ent in regions of heavy lymphocytic infiltration and cell proliferatio n. No other types of benign or malignant thyroid tumours were found. I n contrast to BB/W rats, Wistar rats showed no lymphocytic infiltratio n, cell proliferation or increased SCN occurrence in the thyroid gland . We conclude that in an animal model predisposed to autoimmune thyroi ditis, excess iodine stimulates the development of aberrant cell proli feration and the formation of thyroid SCN. Although the clonal origin of these cells is debated, thyroid SCN may be considered as a precurso r to thyroid cancer. The present study establishes a link between the level of iodine intake and the development of thyroid neoplasia to whi ch lymphocytic thyroiditis may also be a contributor.