Excess Iodine Induces the Expression of Thyroid Solid Cell Nests in Lymphocytic Thyroiditis-Prone BB/W Rats

Abstract

Previous epidemiological studies have suggested that lymphocytic thyroiditis and/or an increased iodine intake may be risk factors for the development of thyroid cancer. We previously reported that excess iodine accelerated the development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat model. We also found that excess iodine increased thyroid cell proliferation in a disordered manner. The present study was designed to further explore these observations and to address the question as to whether excess iodine under certain conditions predisposes the thyroid gland to neoplasia.

To test this hypothesis, the 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 water (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 also divided into excess iodine and control groups, served as a comparison 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 accompanied by prominent thyroid cell proliferation, evident as numerous microfollicles and cell masses, not forming normal thyroid follicles. Numerous lymphocytes and plasma cells often encroached on these areas of increased cellular proliferation. The surprising feature, and a possible indicator of activated thyroid cell proliferation, was the high incidence of thyroid solid cell nest-like lesions (SCN) in the iodine treated BB/W rats. Two main types of SCN were identified in the BB/W rat thyroid; the first was the solid epidermoid or squamous cell variant and the second type was cystic in structure and was lined by epithelial cells, with eosinophilic material or desquamated cells filling the centre. The incidence of SCN was markedly higher in the excess iodine group (70%) than that in the control group (10%). Thyroid SCN in iodine treated rats were generally much larger and more cystic compared with those seen in the rat with normal iodine status. SCN were more often present in regions of heavy lymphocytic infiltration and cell proliferation. No other types of benign or malignant thyroid tumours were found. In contrast to BB/W rats, Wistar rats showed no lymphocytic infiltration, cell proliferation or increased SCN occurrence in the thyroid gland.

We conclude that in an animal model predisposed to autoimmune thyroiditis, excess iodine stimulates the development of aberrant cell proliferation and the formation of thyroid SCN. Although the clonal origin of these cells is debated, thyroid SCN may be considered as a precursor to thyroid cancer. The present study establishes a link between the level of iodine intake and the development of thyroid neoplasia to which lymphocytic thyroiditis may also be a contributor.