Week 9

• The thyroid gland is an endocrine gland that is ductless and secretes hormones into circulation, affecting distant sites.
• The thyroid gland is bilobed or butterfly shaped and sits anteriorly in the neck, caudal to the larynx, encircling the trachea.
• Novel insights into thyroid hormones can be gained from the study of common genetic variation.
• The thyroid gland is highly vascular, with an arterial supply from the superior (from the external carotid) and inferior (from the subclavian) thyroid artery.
• The thyroid gland weighs 20g in humans and is embryologically derived from the endoderm from week 3 of gestation.
• The thyroid gland synthesises and secretes thyroid hormones by 12 weeks: Thyroxine (T4) and Tri-iodotyronine (T3).
• The thyroid gland is made up of follicles 0.2 - 0.9mm, which are secretory cells for thyroid hormones.
• Follicles have a single layer of cuboid cells with lumen filled with colloid (mucus like fluid) containing thyroglobulin (iodinated glycoprotein), binding T4 and T3.
• C-cells/parafollicular cells, neural crest origin, secrete calcitonin, which regulates calcium.
• Thyroid hormones are derived from tyrosine (amino acid) with incorporation of inorganic IODINE.
• T4 (thyroxine) and T3 (Tri-iodotyronine) are made of a combination of Monoiodotyrosine (MIT) and Diiodotyrosine (DIT).
• T4 (thyroxine) is the circulating prohormone that converts to T3 in target tissues (via deiodination).
• T3 (Tri-iodotyronine) is secreted in small quantities and is the major active form in target cells.
• Iodine in diet is essential for thyroid hormone synthesis.
• The synthesis of T4/T3 (iodotyrosines) happens within the thyroglobulin molecule.
• Thyroid iodide transport is a crucial step in thyroid hormone synthesis.
• Tyrosyl iodination is a step in thyroid hormone synthesis.
• Hormone release occurs at the apical and basolateral membranes of the thyroid epithelial cell.
• The iodine pump is a key component in hormone release.
• Thyroid hormone secretion involves the action of TSH, TPO, colloid and TG.
• Thyroid hormones bind to 4 carrier proteins: Tyroxine binding globulin (TBG), Transthyretin (TTR) / Thyroxine binding prealbumin (TBPA), Albumin, Lipoproteins.
• T4 binds to TBG (75%)>Albumin (12%)>TTR(10%)>Lipoproteins (3%).
• T3 binds to TBG (80%)>Albumin (13%)> TTR(5%)>Lipoproteins (2%).
• 99.5% T3 is bound while 99.98% of T4 is bound.
• T4 is converted to T3 by 5’ - deiodinase, which is 4 times more potent than T3.
• The thyroid hormone receptors come in at least 2 forms: Alpha and beta receptors.
• The hypothalamo-pituitary-thyroid axis involves TRH stimulating TSH production in the pituitary, which is then secreted and acts on the thyroid gland to secrete T3 and T4 (T4>T3).
• T4 is converted to T3 in target cells.
• Peripheral T4 and T3 will inhibit TSH and TRH synthesis and release.
• TSH will determine the amount of T3 and T4 synthesis.
• The metabolism of thyroid hormones occurs in the liver, kidney, brain, and muscle.
• T4 metabolism occurs via deiodination, with 30 - 40% conversion to T3, 50% conversion to rT3, and 20% T4 and 100% T3 conjugates to glucuronic/sulfuric acid.
• The physiological actions of thyroid hormones include metabolic effects, cardiovascular effects, and growth promoting/developmental effects.
• Disorders of the thyroid gland include hypothyroidism and hyperthyroidism.
• Coupling of MIT/DIT to form T4 and T3 within thyroglobulin molecule is a step in thyroid hormone synthesis.
• Endocytosis of colloid is a step in thyroid hormone synthesis.
• T3 and T4 are lipid-soluble hormones that easily enter into the target cells and bind to nuclear receptors, called Hormone Response Elements (HREs) on DNA.

  
  

  This activates the synthesis of mRNA and subsequently different proteins involved in energy metabolism, growth, differentiation and other functions
• Thyroid disorders predominantly affect women, as many of these disorders are autoimmune in nature and women are more prone to autoimmune diseases
• Hashimoto’s thyroiditis is an autoimmune disorder where there is destruction of thyroid tissue resulting in hypothyroidism.
• Graves' disease is caused by antibodies against the TSH receptor which stimulates it excessively leading to hyperthyroidism.