Nodules formation in goiter is still poorly understood due to the lack of an adequate animal model. The key role of iodine in the increased heterogeneity of iodine metabolism and in cold follicle formation has been demonstrated. Administration of iodide excess to goitrous mice induces follicle cell necrosis and thyroiditis. Necrosis and inflammation can be prevented by reducing the iodine dose, giving T3 or T4, or combining iodide with antithyroid drugs or vitamin E. This suggest that iodide toxicity is related to excessive production of free radicals. During inflammation, Ia positive interstitial cells were increased in number whereas no Ia expression was seen in follicular cells.