Kuwait Pharmacy - Drug Information. Physiology and Tests of Thyroid Function. Thyroid hormone influences a wide range of processes, including growth, development, maturation of the nervous system, reproduction, metabolism, and muscle function. The primary target organs include the brain, liver, skeletal muscle, heart, and bone. The thyroidal secretion consists of thyroxine (T4) and triiodothyronine (T3). T3 is the active form of thyroid hormone and combines with a specific nuclear receptor that binds to the regulatory region of genes and modifies expression. Thyroid hormone synthesis and secretion is regulated by TSH secreted from the anterior pituitary, which in turn is stimulated by thyrotropin- releasing hormone (TRH) from the hypothalamus. Both TSH and TRH are regulated in a negative feedback loop by circulating T4 and T3. Iodine, a trace element, and selenium (see later discussion) are essential for normal thyroid hormone metabolism. The mechanisms that regulate thyroid hormone metabolism allow for continuous production of thyroid hormone despite variation in the supply of dietary iodine. There are also maternal and fetal modifications of thyroid hormone metabolism associated with various stages of pregnancy that maintain a euthyroid state for mother and fetus. Iodine Transport. The majority, 7. 0–8. To produce the daily requirement of thyroid hormone, the thyroid must trap approximately 6. The iodine that is not trapped by the thyroid is excreted in the urine and closely matches dietary intake. Iodine uptake in the thyroid is an active process, driven by the Na+ gradient generated by Na+/K+ adenosine triphosphatase (see Fig. The Na+/I- symporter is a membrane- bound protein located in the basolateral portion of the thyroid follicular cell. The symporter passively transports two Na+ and one I- down the Na+ ion gradient, producing an iodine gradient from the thyroid cell to the extracellular fluid of 1. In conditions of iodine deficiency, a gradient as high as 4. Other tissues that concentrate iodine include the salivary gland, gastric mucosa, lactating mammary gland, ciliary body of the eye, skin, placenta, and choroid plexus. Iodine transport is stimulated by TSH via cyclic adenosine monophosphate (c. AMP) and can be competitively inhibited. Inhibitors of iodine transport include natural dietary 'goitrogens', such as the cyanogenic glucosides found in cassava, a staple in many parts of Asia and Africa, as well as perchlorate and high concentrations of iodine. The primary source of iodine is in the diet, about 2. United States, but there are a number of areas worldwide, especially mountainous regions of Africa, Asia, and some parts of Europe, with dietary iodine deficiency. The offspring of iodine- deficient woman have a high incidence of cretinism with severe neurologic deficit and growth retardation. Even in areas of marginal iodine insufficiency, such as Belgium, there is a reduction in maternal circulating thyroid hormones and an elevation in serum TSH concentration compared to pregnant women from iodine- sufficient areas. The influence of these changes on fetal development are unknown. Levothyroxine is typically used to treat hypothyroidism, and is the treatment of choice for people with hypothyroidism, who often require lifelong. Title: Pituitary Disorders Author: Thomas Repas Last modified by: Thomas Repas Created Date: 9/8/2005 5:55:03 PM Document presentation format: On-screen Show. T3 is one of the two major hormones released from the thyroid. It is also the more important one because it is more potent than T4. Therefore, T3 level is crucial to. Thyroid Hormone Synthesis. Thyroid hormone synthesis requires a number of components, including iodide, thyroid peroxidase, thyroglobulin, and hydrogen peroxide (H2. O2). 1 Iodine is transported into the thyroid in the inorganic form, is oxidized by the thyroid peroxidase- H2. O2 system and then used to iodinate tyrosyl residues in thyroglobulin (see Fig. T4 and T3 are produced by coupling of iodinated tyrosyl intermediates, which are then hydrolyzed and secreted into the circulation. The function of this system requires that these processes are closely linked, and defects in any of the components can lead to impairment of thyroid hormone production or secretion. Thyroglobulin, a large dimeric glycoprotein (6. Find pharmacy related books here. CD: Crohn\'s disease?(R): Right?/d: Per day?1/ SCr: Inverse of serum creatinine?1/2NS: Half-strength normal saline?3D CRT: Three. Liotrix is a 4:1 mixture of thyroxine (T 4) and triiodothyronine (T 3) made synthetically. It is used to replenish thyroid hormones in thyroid deficiency and. ABBREVIATIONS AND ACRONYMS IN BIOMEDICAL RESEARCH AND PRACTICE : A TO J (You may also try searching in a shorter Italian version) An abbreviation is a shortened form. A small amount of thyroglobulin can be detected in the serum and is, in general, proportional to the thyroid mass. The generation of H2. O2 is essential for the iodination of thyroglobulin and subsequent coupling reactions. Explore the Overview of Thyroid Function from the Professional Version of the Merck Manuals. Schecter Conference Hypo/Hyperthyroid, Thyroiditis, Thyroid nodules, Thyroid CA Ginger Xu PGY-3 General Surgery Oct 27, 2010. Amount Per Serving % Daily Value Niacin (as Niacinamide): 20 mg 100% Vitamin B6 (as Pyrodoxine HCL): 3 mcg 150% Vitamin B12. Thyroid hormone influences a wide range of processes, including growth, development, maturation of the nervous system, reproduction, metabolism, and muscle function. Reduction of molecular oxygen to H2. O2 requires reduced adenosine nucleotide, nicotinamide adenine dinucleotide phosphate (NADPH), and NADPH oxidase. Thyroglobulin serves as a substrate for coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT) by the thyroid peroxidase- H2. O2 system. A tyrosyl phenolic ring is cleaved and joined to an iodinated tyrosine by an ether linkage. Coupling of two DIT moieties forms T4, and coupling of MIT and DIT forms T3. The thyroidal secretion usually contains approximately 8. T4 and 2. 0% T3, but this ratio can be altered by a number of conditions, including the extent of TSH stimulation and iodine status. The TSH receptor- stimulating Ig. G of Graves' disease increases the fraction of T3 in the thyroidal secretion by preferential MIT/DIT coupling. Additionally, intrathyroidal type I 5. Pinocytosis produces multiple vesicles containing colloid, which fuse with lysosomes to form phagolysosomes. The resulting proteolysis in these vesicles releases iodothyronines, which diffuse across the cell and into the cytoplasm. Thyroid peroxidase is a membrane- bound glycoprotein that catalyzes the oxidation of iodine, iodination of tyrosine residues, and coupling of iodothyronines. The human thyroid peroxidase gene is 1. The predicted protein consists of 9. TTF1 and TTF2 regulate thyroid peroxidase gene expression. Circulating Ig. G antibodies to thyroid peroxidase are pathogenic in a number of thyroid diseases, including Hashimoto's disease and postpartum thyroiditis. These antibodies can damage the thyroid follicular cells directly by activating the complement cascade. Thyroid Hormone Transport. Thyroid hormones are hydrophobic, and the vast majority of hormone circulates bound to serum proteins with only a small free fraction of T4 (0. T3 (0. 3. 0%). 1. The free hormone is the only metabolically active fraction of the total hormone concentration. The predominant thyroid hormone binding serum protein is T4- binding globulin (TBG), which carries approximately 7. T4 and the majority of T3. Transthyretin (previously called T4- binding prealbumin) binds approximately 2. T4 and also transports retinol by forming a complex with retinol- binding protein. The remaining serum T4 and T3 are bound by albumin. All three of these proteins are made in the liver, and their levels—as well as levels of total thyroid hormone—are influenced by liver disease (elevated in hepatitis, reduced in chronic liver insufficiency) and renal disease (excessive loss in the urine in nephrotic syndrome). TBG consists of approximately 2. Estrogen increases the extent of sialylation and increases serum TBG concentration by prolonging the circulating half- life. Mutations of the TBG gene, located on the X chromosome, can result in partial or complete deficiency. Affected persons have reduced total thyroid hormone concentration but normal levels of free hormone and are clinically euthyroid. Thyroid Hormone Metabolism. The thyroidal secretion is primarily the prohormone T4, which is metabolically inactive and must be converted to the active hormone T3 by removal of the 5. Approximately 2. 0% of circulating T3 is derived from thyroidal secretion and 8. T4, primarily in the liver, muscle, and kidney. T4 can also be converted to reverse T3 (r. T3), which is metabolically inactive; however, when elevated in the serum, it is usually associated with reduced T4 to T3 conversion (e. Degradation products (containing 3–0 iodides) undergo sulfation and glucuronide formation for excretion in urine and bile. Fig. Structure of L- thyroxine (T4) and its major metabolites, triiodothyronine (T3) and reverse triiodothyronine (r. T3). In Conn PM, Melmed S . Totowa, NJ, Humana Press, 1. The deiodinases can be separated into outer ring (phenolic) 5. All deiodinases share the property of being selenoproteins that contain the amino acid selenocysteine, essential for full catalytic activity. The trace element selenium is required for normal thyroid hormone metabolism, and abnormal thyroid function is seen in areas of selenium deficiency, such as China and Africa. Table 1. Properties of iodothyronine deiodinases. Type I 5'- Deiodinase. Type II 5'- Deiodinase. Type III 5- Deiodinase Tissue distribution. Thyroid, liver, kidney. Brain, pituitary, brown fat, thyroid. Placenta, developing brain, skin. Preferred substrater. T3> > T4> T3. T4> T3. T3(sulfate) > T4. Target. Outer ring. Outer ring. Inner ring. Response to T4. Increase. Decrease. Increase. Inhibition by PTUYes. No. No. Inhibition by iodine contrast agents. Yes. Yes. Yes. Physiologic role. Extracellular T3 production. Intracellular T3 production. Inactivation of T4 and T3. T4 = thyroxine; T3 = triiodothyronine; r. T3 = reverse T3; PTU = propylthiouracil. Type I 5. It requires reduced thiol as a cofactor and is sensitive to inhibition by propylthiouracil, starvation, illness, glucocorticoids, and propranolol. The type I gene is positively regulated by T3, and its activity increases in hyperthyroidism. Type II 5. The brain, unlike the periphery, derives the majority of T3 locally from T4 by the action of type II deiodinase. In hypothyroid states, type II 5. It inactivates T4 and T3 by removal of a tyrosyl ring iodide. Like type I, the type III gene is positively regulated by T3. This enzyme is expressed very early in development and may be important in regulating maternal and fetal thyroid hormone metabolism. The Hypothalamic- Pituitary Axis. The primary regulator of thyroid hormone production is TSH. TSH is a heterodimeric protein that shares a common alpha subunit with the other anterior pituitary glycoproteins (follicle- stimulating hormone, luteinizing hormone . Although elevated circulating T3 levels alone will suppress TSH, circulating T4, via intrapituitary type II 5. T4 and T3 also provide feedback to TRH. TRH stimulates TSH as well as prolactin, and T3 inhibits expression of the TRH gene. TSH acts via the membrane- bound TSH receptor. Overview of Thyroid Function - Endocrine and Metabolic Disorders. The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones: Tetraiodothyronine (thyroxine, T4)Triiodothyronine (T3)These hormones act on cells in virtually every body tissue by combining with nuclear receptors and altering expression of a wide range of gene products. Thyroid hormone is required for normal brain and somatic tissue development in the fetus and neonate, and, in people of all ages, regulates protein, carbohydrate, and fat metabolism. T3 is the most active form in binding to the nuclear receptor; T4 has only minimal hormonal activity. However, T4 is much longer lasting and can be converted to T3 (in most tissues) and thus serves as a reservoir for T3. A 3rd form of thyroid hormone, reverse T3 (r. T3), has no metabolic activity; levels of r. T3 increase in certain diseases. Additionally, parafollicular cells (C cells) secrete the hormone calcitonin, which is released in response to hypercalcemia and lowers serum calcium levels (see Overview of Disorders of Calcium Concentration : Regulation of Calcium Metabolism).
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