Thyroid Factor

The Natural Thyroid Diet

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Thyroid function is regulated by a negative feedback loop involving the hypothalamus, pituitary, and thyroid gland. Thyrotropin releasing hormone (TRH, or thyroliberin) is released from the hypothalamus into the portal circulation of the pituitary, where it stimulates the pituitary to release thyroid stimulating hormone (TSH, or thyrotropin). TSH in turn stimulates the synthesis and release of thyroxine

Fig. 1.2. Arterial supply of the thyroid. A thyroid ima artery is present in less than 10% of the population.
Fig.1.3. Lymphatic drainage of the thyroid

(T4) from the thyroid gland. Thyroxine inhibits the release of TRH from the hypothalamus and TSH from the pituitary, thus forming a negative feedback loop. Virtually all steps of thyroid hormone synthesis and release are stimulated by TSH, including the gland's iodine trapping mechanism. TSH binds to membrane receptors on follicular cells and stimulates production of cyclic adenosine monophosphate (cAMP), which leads to increased uptake of iodide (I-) into the follicular cell. Iodide is actively transported into the follicular cell, against a 20- to 40-fold concentration gradient. This gradient is even higher in the presence of TSH and/or a low extracellular iodine concentration. This increase in active transport of iodide into the follicular cell in the face of low plasma iodide concentration is referred to as thyroid autonomy. Iodide then diffuses into the follicular lumen, where thyroperoxidase uses hydrogen peroxide to oxidize it to form I-. Thyroperoxidase then catalyzes the binding of I- to tyrosine residues in the thyroglobulin matrix to produce diiodotyrosine (DIT) or monoiodotyrosine (MIT).

Thyroglobulin is a polypeptide containing an average of 140 tyrosine residues. It is produced in the rough endoplasmic reticulum of the follicular cell and extruded into the follicular lumen. Iodination of tyrosine increases with increasing extracellular concentration of iodine to a maximal rate. Above a certain extracellular iodine concentration (about 25 |ig /dl), iodination of tyrosine is inhibited. This phenomenon, called the Wolff-Chaikoff effect, is the basis for acute treatment of hyperthy-roidism with exogenous iodine. The thyroid adapts to this high iodine level and escapes this inhibition within several days, so that this treatment is only temporarily effective. A minimum of 75 |Jg of dietary iodine intake is required daily for adequate thyroid function. The average American ingests 500 |ig per day primarily in drinking water, eggs, iodized salt, bread, milk, and seafood. It is absorbed as iodide ion (I-) after being reduced from inorganic iodine (I"). The normal thyroid contains a reserve of about 8000 g of iodine, with about 1% of this pool turned over per day.

Thyroperoxidase catalyzes the coupling of DIT to DIT to form tetraiodothyronine (T4 or thyroxine), or the coupling of MIT to DIT to form triiodothyronine (T3). This coupling takes place in the follicular lumen. TSH stimulates resorption of thyroglobulin into the follicular cell by pinocytosis. This allows lysosomal proteases to split T4 and T3 as well as MIT and DIT residues from the thyroglobulin matrix. T4 and T3 are released into the circulation from the basal surface of the cell. The MIT and DIT residues released from thyroglobulin are deiodinated so that the iodine can be recycled. Normally, about 80 |mg of T4 and 6 |ig of T3 are made each day. About 70% of both T4 and T3 are bound to thyroid binding globulin (TBG), a glycoprotein produced by the liver. This bond is reversible, and each TBG molecule has the capacity to bind one iodothyronine molecule. Prealbumin (transthyretin) and albumin bind almost all of the remaining iodothyronines, leaving only 0.03% of T4 and 0.30% of T3 in their free state. Thyroxine has a much higher affinity for these proteins than does T3, accounting for its longer half-life (7 days, versus 1 day for T3). The concentration of TBG is influenced by hormones, drugs, and disease states. These states may alter the plasma concentration of total T4 or T3 (protein bound + free hormone), even though the concentration of the active forms, free T4 or T3, may be unaltered (see Table 1.1). This makes the measurement of total T4 or

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