The Role of Iodine Deficiency and Subsequent Repletion in Autoimmune Thyroid Disease and Thyroid Cancer

Iodine is an essential trace mineral that is necessary for thyroid hormone production. With the prevalence of iodine deficiency worldwide, universal salt iodization programs were successfully implemented to reduce the incidence of iodine deficiency disorders; however, unexpected increases in the prevalence of thyroid autoimmunity occurred, and iodine excess was implicated as the causative factor. Despite these observations, epidemiological studies are inconsistent, and the etiology of autoimmune thyroid disease remains undefined. A review of observational and in vitro studies revealed that iodine alone is not responsible for thyroid autoimmunity. Experimental models used to explain iodine excess as the culprit in thyroid autoimmunity fail to induce thyroid autoantibodies unless iodine is in the presence of excess inflammatory cytokines (interferon [IFN]-γ) and hydrogen peroxide (H 2 O 2 ). Within iodine-deficient populations, regulatory mechanisms to limit oxidative stress and excess iodine are lost. Thyroid-stimulating hormone persistently activates the sodium-iodide symporter, while iodine concentrations fail to achieve levels high enough to produce iodolactones, which are responsible for modulating NADPH oxidase and H 2 O 2 production. Subsequently, the thyroid becomes susceptible to oxidative stress as iodine is reintroduced. Oxidation of thyroid peroxidase and thyroglobulin initiate the release of inflammatory cytokines (IFN-γ) and lymphocytic infiltration, which induce autoantibody production and thyroid autoimmunity. Population studies revealed that iodine administration even below the recommended dietary allowance alters thyroid autoimmunity. Despite increases in thyroid antibodies, these changes are found to be transient. Interestingly, reports of iodine in combination with other nutrients and standardized botanical extracts have been used successfully to restore thyroid function. On the basis of our review of the literature, it is apparent that a loss of regulatory mechanisms due to preexisting iodine deficiency followed by iodine repletion, as opposed to iodine excess, is a causal factor in the development of thyroid autoimmunity.