Hormones thyroglobulin

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... 

Determine if there is expression of cell-specific products, cell-specific structures, and transcription factors or receptors that are unique identifiers of cell types (e.g., neuroendocrine granules, peptide hormones, thyroglobulin, PSA, prostate-specific membrane antigen, inhibin, gross cystic disease fluid protein [GCDEP], villin, uroplakin, thyroid transcription factor-1 [TTE-1] or transcription factor CDX-2). 

The expression of the sodium iodide symporter is perhaps nowhere more important than in the thyroid gland. A complete review of the physiological importance of the thyroid is beyond the scope of this chapter. It is sufficient to say that the symporter provides the iodine needed for normal thyroid function. Once the symporter has been trafficked to the basolateral surface of the thyrocyte, it can transport iodine from the blood into the cell. Once inside the cells, iodine is transported to the apical membrane where it is organified through attachment to a tyrosine residue and incorporated into the thyroid hormone thyroglobulin. The thyroglobu-lin is then stored inside thyroid follicles as colloid, to be released into the bloodstream as thyroid hormones (thyroxine and triiodothyronine) via TSH stimulation. 

Conceptually the whole field of iodine nutrition may be subdivided into two broad subdivisions, the process and the impact (or outcome) fields of iodine nutrition, each with its own assessment indicators. The impact side of the iodine nutrition field represents the response of the human body to the iodine delivered to and consumed by the consumer, and therefore follows the process phase sequentially. This response of the human body is usually assessed in terms of impact indicators, such as the median urinary iodine concentration, thyroid size, and blood constituents such as thyroid-stimulating hormone, thyroglobulin, or other thyroid hormones. The process side of iodine nutrition covers factors playing a role in the delivery of iodine to the consumer via iodized salt or via an alternative source, such as processed food, drinking (iodine-containing cleaning agents) used in the dairy industry water or iodophors. 

Other important monitoring parameter for thyroid carcinoma is the presence of tumor cells in bone marrow or the circulation of tumor cells in peripheral blood. For the detection of these tumor cells, molecular methods based on the detection of tissue-specific gene expression are developed. The most efficient molecular marker is mRNA encoding to the thyroid-specific hormone thyroglobulin (Tg), a further target is mRNA encoding specific enzymes involved in the synthesis of thyroid hormones such as thyroid peroxidase (TPO). Thyroid transcription factor-1 (TTF-1) is another thyroid-specific marker, which can be used for the diagnosis of thyroid tumors. 

When stimulated to release thyroid hormones, thyroglobulin is degraded through the activity of lysosomes and T3 and T4 are released and rapidly enter the circulation. Iodide freed in this reaction is for the most part recycled and the iodinated tyrosine reused for hormone production. Nearly all of the released hormones are rapidly bound to transport hormones, with 70% bound to thyroxine binding globulin (TBG). Other proteins, such as transthyretin (TTR), albumin, and lipoproteins, bind most of the remainder with significant differences in the strengths of the affinity for the hormones, these proteins transport the hormones to different sites. 

Thyroid Hormones. Iodine, absorbed as P, is oxidized in the thyroid and bound to a thyroglobulin. The resultant glycoprotein, mol wt 670,000, contains 120 tyrosine residues of which ca two-thirds are available for binding iodine in several ways. Proteolysis introduces the active hormones 3,5,3 -triiodothyronine (T ) and 3,5,3, 5 -tetraiodothyronine (T, (thyroxine) in the ratio Ty.T of 4 1 (121,122). 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Thyroglobulin A thyroid hormone-containing protein, usually stored in the colloid within the thyroid follicles. 

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. 

Thyroid hormones. Internally, the thyroid consists of follicles, which are spherical structures with walls formed by a single layer of epithelial cells called follicular cells. The center of each follicle contains a homogenous gel referred to as colloid. Thyroid hormones are stored here as a component of the larger molecule, thyroglobulin. The amount of thyroid hormones stored within the colloid is enough to supply the body for 2 to 3 months. 

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. 

The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin. 

Amiodarone may induce thyrotoxicosis (2% to 3% of patients) or hypothyroidism. It interferes with type I 5 -deiodinase, leading to reduced conversion of T4 to T3, and iodide release from the drug may contribute to iodine excess. Amiodarone also causes a destructive thyroiditis with loss of thyroglobulin and thyroid hormones. 

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. 

Sodium iodide 131 is an oral liquid that concentrates in the thyroid and initially disrupts hormone synthesis by incorporating into thyroid hormones and thyroglobulin. Over a period of weeks, follicles that have taken up RAI and surrounding follicles develop evidence of cellular necrosis and fibrosis of the interstitial tissue. 

Excessive doses of thyroid hormone may lead to heart failure, angina pectoris, and myocardial infarction. Allergic or idiosyncratic reactions can occur with the natural animal-derived products such as desiccated thyroid and thyroglobulin, but they are extremely rare with the synthetic products used today. Excess exogenous thyroid hormone may reduce bone density and increase the risk of fracture. 

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...

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

Thyroid-stimulating hormone (TSH thyrotropin) In patients who have been treated surgically for thyroid carcinoma, to test for recurrence by assessing TSH-stimulated whole-body 131I scans and serum thyroglobulin determinations... 

Thyroid Hormones The thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) are synthesized from the precursor protein thyroglobulin (Mr 660,000). Up to 20 Tyr residues in thyroglobulin are enzymatically iodinated... 

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