Adaptation to iodine deficiency: Experimental aspects: T4 and T3 in plasma and different tissues

Abstract

This chapter stresses the importance of TSH-independent autoregulatory responses that are rapidly activated by mild ID, including an increase in thyroid weight and activation of the preferential synthesis of T3 over T4, resulting in the maintenance of elevated, or normal, circulating T3, even in severe ID. Very severe ID is needed to decrease the circulating T3 below normal values. Experimental models of ID have afforded important relevant information for man. Any degree of ID, even if mild, ought to be avoided because it rapidly activates TSH-independent autoregulatory mechanisms that result in goiter, and an increased incidence of thyroid disorders accompanying thyroid hyperplasia. A combination of intra- and extrathyroidal mechanisms of adaptation leads to the preferential synthesis and secretion of T3 over T4, as a consequence of which circulating T3 levels are normal, or even increased, at the expense of decreasing circulating T4 concentrations. Circulating T3 only decreases in situations of very severe ID. Extrathyroidal consequences of the changes in circulating T4 and T3 are not the same for all tissues. At all degrees of ID, indices of thyroid hormone status are clearly tissue specific: elevated, normal, and low concentrations of T3 are found in different tissues of the same animal. circulating T3 has to decrease before many T3-dependent tissues become hypothyroid. This appears to occur when circulating T4 decreases from 25% to 5% of normal values. But even under such conditions, the many known and as yet undefined intra- and extrathyroidal adaptive mechanisms are efficient enough to maintain euthyroidism in muscle and heart, and even slightly elevated T3 in lung and ovary.