TSH regulates thyroidal iodine metabolism by activation of adenylate cyclase. This facilitates endocytosis as a component of iodide uptake, digestion of thyroglobulin-containing colloid, and the release of thyroid hormones T4,T3, and reverse T3.T4 is released from the thyroid at 40 to 100 times the concentration of T3. The concentration of reverse T3, which has no intrinsic thyroid activity, is 30% to 50% of T3, and 1% of T4 concentration. Of thyroid hormones released, 70% are bound by circulating thyroid-binding globulin (TBG). T4 is present in higher concentrations in the circulating storage pool and has a slower turnover rate than T3. Approximately 30% of T4 is converted to T3 in the periphery. Reverse T3 participates in regulation of the conversion of T4 to T3.T3 is the primary physiologically functional thyroid hormone at the cellular level. T3 binds the nuclear receptor with 10 times the affinity of T4. Thyroid hormone effects on cells include increased oxygen consumption, heat production, and metabolism of fats, proteins, and carbohydrates. Systemically, thyroid hormone activity is responsible for the basal metabolic rate. It balances fuel efficiency with performance. Hyperthyroid states result in excessive fuel consumption with marginal performance.
Iodide Metabolism Normal function of the thyroid gland is dependent on iodine. The World Health Organization recommends 150 μg of iodine per day in women of reproductive age and 250 μg per day is recommended during pregnancy and nursing. Adequate iodination of household salt is defined as salt containing 15 to 40 mg of iodine per kilogram of salt (333).
Optimal iodine intake to prevent disease lies within a relatively narrow range around the recommended daily consumption. Extreme iodine deficiency states are associated with cretinism, goiter, and hypothyroidism, while iodine sufficiency is associated with autoimmune thyroid disease and reduced remission rates in Graves disease (334).
Environmental factors associated with the occurrence of autoimmune thyroid diseases include pollutants (plasticizers, polychlorinated biphenyls) and exposure to infections such as yersinia enterocolitica, coxsackie B, Helicobacter pylori, and hepatitis C (335,336). For reasons not entirely known, women experience a 5-to 10-fold increased incidence of autoimmune thyroid disease (337). This difference is postulated to be the result of differences in sex steroid hormone levels, differences in environmental exposures, innate differences in female and male immune systems, and inherent chromosomal differences in the sexes (338,339). The immunoglobulins produced against the thyroid are polyclonal, and the multiple combinations of various antibodies consolidate to create the clinical spectrum of autoimmune thyroid diseases that may affect health and reproductive function.
Thyroid Function Measurements of free serum T4 and T3 are complicated by the low levels of free hormone in systemic circulation, with only 0.02% to 0.03% of T4 and 0.2% to 0.3% of T3 circulating in the unbound state (340). Of the T4 and T3 in circulation, approximately 70% to 75% is bound to TBG, 10% to 15% attached to prealbumin, 10% to 15% bound to albumin, and a minor fraction (<5%) is bound to lipoprotein (340,341). Total thyroid measurements are dependent on levels of TBG, which are variable and affected by many conditions such as pregnancy, oral contraceptive pill use, estrogen therapy, hepatitis, and genetic abnormalities of TBG. Thus, assays for the measurement of free T4 and T3 are more clinically relevant than measuring total thyroid hormone levels.