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The basic functional unit of the thyroid gland is the:
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Thyroid follicle:
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The thyroid follicle is made up of a:
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Single layer of cells that forms a sphere that surrounds a protein aggregate called colloid.
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The thyroid follicular cells are polarized:
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With the side toward the colloid called the:
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Apical membrane
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And the outer side of the cell in contact with capillaries called the:
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Basal membrane (Figure)
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The synthesis of thyroid hormone is activated after binding of:
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Thyrotropin-stimulating hormone (TSH) to the basal membrane surface receptor:
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The TSH receptor
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TSH stimulates all the steps of thyroid hormone synthesis and secretion, including:
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Iodide transport
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Synthesis of thyroglobulin
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Iodination of thyroglobulin
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Secretion of thyroid hormones
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TSH binding of the TSH receptor on the basal membrane of the thyroid follicular cell activates adenylate cyclase:
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To increase intracellular cAMP:
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Which activates a cascade of numerous steps in the thyroid hormone synthetic pathway
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The first step is transport of iodide across the basal membrane into the follicular cell in an energy-dependent manner by the Na+/I symporter:
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The iodide becomes covalently attached to the precursor thyroid hormone glycoprotein:
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Thyroglobulin:
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This occurs at the interface between the apical membrane and the colloid by the enzyme thyroperoxidase (TPO).
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The iodide is attached to the tyrosine molecules in the thyroglobulin molecule to form:
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Monoiodotyrosines (MITs) and diiodotyrosines (DITs).
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TPO enzymatically couples two iodotyrosines to create bioactive thyroid hormones:
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Two diiodotyrosines (DITs) = L-thyroxine (T4)
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One monoiodotyrosine (MIT) and diiodotyrosine (DIT) =triiodothyronine (T3).
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The T4 and T3 remain part of the thyroglobulin molecule and is stored as colloid within the interior of the follicle.
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The thyroid gland is a unique endocrine organ:because it stores large amounts of thyroid hormones as colloid that is released as needed through TSH stimulation.
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In healthy and iodine-sufficient individuals:
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The majority of thyroid hormone is stored as T4 with a small amount, less than 20%, stored as T3.
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TSH receptor stimulation leads to colloid uptake into the cytoplasm by pinocytosis to form a cytoplasmic vesicle:
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The cytoplasmic vesicles fuse with lysosomes to from a phagolysosome and the proteases found within the lysosome hydrolyze the peptide bonds of thyroglobulin to release T4 and T3 into the cytoplasm where it diffuses into the bloodstream.
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Approximately 90 mcg of T4 is secreted from the thyroid each day in adults.
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T4 and T3 travel in the circulation bound 99.97% and 99.5%, respectively, to a group of serum thyroid hormone binding proteins synthesized in the liver, which include:
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Thyroxine binding globulin (TBG), transthyretin (also known as prealbumin), and albumin.
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TBGhas the highest affinity to bind thyroid hormone and is clinically the most important member of this group:
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TBG carries about 68% of the circulating T4 and 80% of the T3.
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Transthyretin, formally named prealbumin binds with a lower affinity and carries 11% of the circulating T4 and 9% of T3.
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Albumin has the lowest affinity for thyroid hormone but the largest capacity, binding 20% of the T4 and 11% of the T3.
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More than 99% of thyroid hormones circulate bound to these carrier proteinsand are biologically inactive.
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The half time of T4 in the blood is 7 to 10 days.
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The thyroid hormones not associated with protein, free T4 and free T3, can enter the cells and are biologically active.
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T4 is made exclusively by the thyroid gland, whereas T3 is made primarily in peripheral tissues by deiodination of circulating T4 by a group of enzymes called deiodinases:
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Deiodinase enzyme activity is tightly regulated to maintain a normal T3 despite fluctuations in T4.
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T3 binds with a much higher affinity to the thyroid hormone receptor and is more biologically active than T4.
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The activity of a specific 5′-deiodinase and the resulting T3 level can be reduced by:
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Hyperthyroidism
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Drugs:
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Beta-blockers
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Ipodate
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Amiodarone
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Dexamethasone
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Propylthiouracil,
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Malnutrition
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Severe illness.
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Conversely, during hypothyroidism, the 5′ deiodinase is activated to ensure that T4 is converted to the more bioactive T3.
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Normally, 20% of the daily T3 requirement is directly synthesized and secreted by the thyroid gland:
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During starvation and illness:
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The 5′ deiodinase converts the bioactive T4 and T3 to biologically inactive molecules:
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Reverse T3 (rT3) and 3, 3′ diiodothyronine
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The small quantity of free T3 binds to its intranuclear thyroid hormone receptor to alter gene expression:
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Which in turn alters cellular function and determines the thyroidal status.
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The thyroid hormone receptor (TR) is a nuclear protein that is a member of a superfamily of receptors that bind steroid hormone such as retinoic acid, vitamin D, and estrogen.
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Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon / endocrine surgeon / surgical oncologist and is a member of Sociedad Quirúrgica S.C at the America British Cowdray Medical Center in Mexico City:
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He is an expert in the management of thyroid and parathyroid diseases.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 