Thyroglobulin gland

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

Thyrotoxicosis factitia should be suspected in a thyrotoxic patient without evidence of increased hormone production, thyroidal inflammation, or ectopic thyroid tissue. The RAIU is low because thyroid gland function is suppressed by the exogenous thyroid hormone. Measurement of plasma thyroglobulin reveals the presence of very low levels. 

Thyroglobulin is a purified hog-gland extract that is standardized biologically to give a T4 T3 ratio of 2.5 1. It has no clinical advantages and is not widely used. 

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

An important product of tyrosine metabolism in vetebrates is the thyroid hormone101 of which the principal and most active forms are thyroxine (T4) and triiodothyronine (T3).102 The thyroid gland is rich in iodide ion, which is actively concentrated from the plasma to 1 pM free I. 103 This iodide reacts under the influence of a peroxidase (see Fig. 16-14 and accompanying discussion)104 to iodinate tyrosyl residues of the very large 660-kDa dimeric thyroglobulin, which is stored in large amounts in the lumen of the... 

Thyroxine (T4) and the more potent triiodothyronine (T3) are cleaved from a large precursor protein called thyroglob-ulin. Thyroglobulin exists as a dimer of two identical polypeptides (Mr 330,000). It is a storage protein for iodine and can be considered a prohormone of the circulating thyroid hormones. Thyroglobulin is secreted into the lumen of the thyroid gland, where specific residues are iodinated in... 

Radioactive isotopes of iodine are handled by the thyroid in the same way as stable iodine and are therefore actively concentrated, incorporated into thyroglobulin, stored, metabolized, and secreted as thyroid hormones. Small amounts of radioactive iodine are therefore ideal probes to analyse the uptake of iodine, the distribution of iodine in the gland, and possibly even its turnover and incorporation into thyroid hormones. Larger amounts of radioactive iodine selectively radiate the thyroid gland and therefore selectively impair the function of the follicular thyroid cells and eventually destroy them. 

The iodinated thyroglobulin is stored as a colloid in thyroidal follicular cells, and T3 and T4 are liberated from it by proteolysis as required. It is estimated that ca 90 Jig of T4 and 6 Jig of T3 are secreted daily by the thyroid gland, giving mean plasma concentrations of 80 and 2 lg/L, respectively, of which only 0.03 and 0.3% are in the free form, ie, not protein bound (21). The half-life of T4 in the body is long (6—7 d) (2) that of T3 is somewhat shorter... 

---