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Follicles and Colloid – Follicular Epithelial Cells –Colloidstores thyroid hormone Parafollicular Cells(C cells) Follicles and Colloid • Calcitonin Thyroglobulin • Iodinated tyrosine molecules • Tetraiodothyronine = T4 =Thyroxine • Triiodothyronine = T3 • Reverse T3 = rT3 = an isomer • 1) Synthesis of Thyroglobulin – Follicular epithelial cells – Tyrosine – Secreted into the Colloid • 2) Iodide Trapping – Plasma into Epithelial Cells – Thiocyanates can block 1 h • 3) Oxidation of Iodide – Thyroid peroxidase • 4) Organification – MIT(monoiodothyronine) – DIT(diiodothyronine) • oxidizes Iodide to form Iodine TPO I¯ Ð I – Thiouracils can block • DIT + MIT = T3(10%) rT3 (<1%) • DIT + DIT = T4(90%) Secretion of Thyroid Hormones • T4 and T3 released from cell into plasma • 5) STORAGE Thryoglobulin • Tyrosine and I are recycled Concept of Bound vs. Unbound • Thyroxine binding globulin (75% T-4; 75% T-3) • Transthyretin (15% T-4; 0% T-3) • Thyroxine binding albumin • Concepts • Clinical Implications (10% T-4; 25% T-3) 2 Thyroid Stimulating Hormone * • • • • Enhances Iodide trapping Enhances synthesis of T4 and T3 Enhances the endocytosis of the colloid Enhances the proteolysis of the thyroglobulin • Enhances the release of T4 and T3 * Starvation inhibits this enzyme • Maturational/Differentiational Mechanism of Action • Neurological Effects • Growth • Metabolic Actions • Sympathomimetic Effect • Reproduction Hypothyroidism • Primary - failure of gland itself • Secondary - TRH or TSH related deficiency • Nutritional (most common world) • Hashimoto thyroiditus most common U.S. 3 • Symptoms (Infants and Children) – – – – – R.D.S. Retarded Bone Age Mental Retardation Stunted Growth Delayed or absent sexual maturity Hypothyroidism Treatment – THYROXINE PREPARATIONS • LEVOXYL • SYNTHROID • LEVOTHYROID • Symptoms (Adults) – – – – – – Low BMR Poor resistance to cold Weight gain Slow thinking Thin and brittle hair Weakness, fatigue, lethargy – MYXEDEMA Hyperthyroidism (Thyrotoxicosis) • Graves’ Disease • Symptoms – – – – Increased BMR Heat Intolerance Increased appetite Elevated HR and arrhythmias, – Nervous, irritable – Exopthalmus Hyperthyroidism • Treatment – Surgery – 131I – Thiouracils – (PROPACIL) 4 Goiter • Enlarged Thyroid Gland • Hyperthyroidism or Hypothyroidism • Iodide deficiency 5