The thyroid gland synthesizes and releases thyroxine (T4) and triiodothyronine (T3) in response to stimulation by TSH, which is secreted by the adenohypophysis. The thyroid gland synthesizes its hormones from iodine and the essential amino acid tyrosine. Most of the body's iodine is ingested as iodide through dietary intake and is absorbed into the bloodstream from the gastrointestinal tract. One-third of the absorbed iodide enters the thyroid gland; the remaining two-thirds is excreted in the urine. In the thyroid gland, enzymes oxidize iodide to iodine.
The thyroid gland secretes a protein, thyroglobulin, into its follicles. Thyroglobulin has special properties that allow the tyrosine contained in its molecules to react with iodine to form thyroid hormones. The thyroid hormones thus formed are stored in the follicles of the gland as the thyroglobulin-thyroid hormone complex called colloid.
When thyroid hormones are released into the bloodstream, they are split from thyroglobulin as a result of the action of proteases, which are secreted by thyroid cells in response to stimulation by TSH. Much more T4 than T3 is secreted into the bloodstream. Upon entering the bloodstream, both immediately combine with plasma proteins, mainly thyroxine-binding globulin (TBG), but also with albumin and prealbumin. Although more than 99 percent of both T4 and T3 are bound to TBG, physiological activity of both hormones results from only the unbound ("free") molecules. Note also that TBG has greater affinity for T4 than for T3, which allows for more rapid release of T3 from TBG for entry into body cells. T3 is thought to exert at least 65 to 75 percent of thyroidal hormone effects, and it is believed by some that T4 has no endocrine activity at all until it is converted to T3, which occurs when one iodine molecule is removed from T4.46
The main function of thyroid hormones is to increase the metabolic activities of most tissues by increasing the oxidative enzymes in the cells. This increase, in turn, causes increased oxygen consumption and increased utilization of carbohydrates, proteins, fats, and vitamins. Thyroid hormones also mobilize electrolytes and are necessary for the conversion of carotene to vitamin A. Although the mechanism is not known, thyroid hormones are essential for the development of the central nervous system. Thyroid-deficient infants may suffer irreversible brain damage (cretinism). Thyroid deficiency in adults (myxedema) produces diffuse psychomotor retardation, which is reversible with hormone replacement. Thyroid hormones also are thought to increase the rate of parathyroid hormone secretion.
Alterations in thyroid hormone production may be caused by disorders affecting the hypothalamus, which secretes thyrotropin-releasing hormone in response to circulating T4 and T3 levels; the pituitary gland; or the thyroid gland itself. Such alterations may affect all body systems. Hypothyroidism is the general term for the hypometabolic state induced by deficient thyroid hormone secretion, whereas hyperthyroidism indicates excessive production of thyroid hormones.
An additional hormone produced by the thyroid gland is calcitonin, which is secreted in response to high serum calcium levels. Calcitonin causes an increase in calcium reabsorption by bone, thus lowering serum calcium.47
A number of tests pertaining to thyroid hormones may be performed, some of which may be grouped as a "thyroid screen" (e.g., T4, T3, and TSH). A "T7" is sometimes ordered. This is interpreted as a T4 plus a T3, because there is no such substance as T7. Before it was possible to measure thyroid hormones directly, serum iodine measurements (e.g., protein-bound iodine) were used as indicators of thyroid function. These tests were severely affected by organic and inorganic iodine contaminants and are no longer used to any great extent. Similarly, measurement of thyroidal uptake of radioactive iodine (131I) has been replaced by direct measurements of T4 and TSH.48