Thyroid gland, thyroid hormones, hypothyroidism, hashimoto thyroiditis, hyperthyroidism, Graves' disease, tachycardia

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Biomedical Science
BMS 460
D.Rao Veeramachaneni

20 November Thyroid Gland: Functional Regulation TRH → pituitary → TSH → TSH receptor on thyroid G protein coupled receptor GTP → GDP ↑ cAMP T 3 T 4 T 3 T4→ thyroid hormone receptor Gene expression on Reverse T 3 3, 3’, 5’ triiodothyronine No biological activity ↑ [Ca] → ↑ calcitonin release by C-cells Clear or parafollicular cells Hypercalcitoninemia Nutritional disorder Thyroid disorder 2+ Calcitonin enables Ca to enter bone → osteopetrosis Thyroid Hormones: T and3T 4 T 4s converted to active T at3target tissue by 5’-diodinase action. The T b3nds to nuclear receptors, initiating transcription of a variety of proteins and enzymes. The overall effects of thyroid hormone are to increase metabolic rate and O 2 consumption. There is a wide spectrum of general effects in target organs. Intracellular effects ↑ mitochondria, respiratory enzymes, Na /K -ATPase, other enzymes → ↑ O 2 consumption, metabolic rate Whole body effects Normal growth and development of bones, central nervous system ↑ CO ,2ventilation in lungs ↑ cardiac output ↑ urea, renal function Thyroid Hormone Production + Iodine is cotransported with Na into follicular cell Diffusion into colloid Iodide is oxidized and attached to rings of tyrosines in thyroglobulin (TG) via thyroid peroxidase TG is synthesized in follicle cell and secreted to colloid The iodinated ring of one MIT or DIT is added to a DIT at another spot Endocytosis of thyroglobulin containing T an3 T mole4ules Lysosomal enzymes release T and T3from TG4 T3, T4secretion; free amino acids re-used for TG synthesis Thyroid Hormones: Clinical Significance: Hypothyroidism Causes Most often caused by Hashimoto’s disease Autoimmune lymphocytic thyroiditis Iatrogenic interventions Surgery or radioactive iodine treatment; drugs such as lithium Dietary Iodine deficiency; ‘goitrogens’ Iodine deficiency is extremely rare in the US because of the widespread use of iodized salt, in which one in every 10,000 molecules of NaCl is replaced with NaI. Sequelae Deficiency of thyroid hormones in general slows down the metabolism, but the clinical presentation depends on the duration and severity of hormone deficiency. Cretinism – deficiency during fetal development Most often caused by maternal hypothyroidism before fetal thyroid is developed Myxedema – deficiency in adulthood Goiter – enlargement of thyroid gland [↑ TSH] Neurologic symptoms Low mental energy Apathy Fatigue Psychotic thoughts Hearing loss Heart Bradycardia (slow pulse) Head and neck Periorbital edema Coarse facial features Protruding tongue Hoarseness Goiter Gastrointestinal system Gastric atrophy Constipation Muscle Proximal muscle weakness Fatigue Atrophy Skin and adipose tissue Edema Fat accumulation Cold, dry skin Intolerance to cold Hands Cold hands Carpal tunnel syndrome Edema Reflexes Slow relaxing Lab for primary hypothyroidism ↓ T4 ↑ TSH Pathogenesis of Hashimoto thyroiditis “Hashitoxicosis” Three proposed models for mechanism of thyroid destruction Sensitization of autoreactive CD4+ T cells to thyroid antigens appears to be the initiating event for all three mechanisms of thyroid cell death T-cell-mediated cytotoxicity CD8+ cytotoxic T-cell kills thyroid cells via Fas-FasL Thyrocyte injury CD4+ T 1Hcell → γ-IFN → activated macrophages Antibody-dependent cell-mediated cytotoxicity Plasma cell → anti-thyroid antibodies NK cell kills via Fc receptor Prominent germinal follicle and heavy infiltrate of lymphocytes throughout the gland with destruction of the thyroid follicles Puffy face, particularly around the eyes; coarse hair Hypothyroidism: Cretinism, Myxedema In the adult, hypothyroidism is manifested by coarse skin with a puffy appearance due to the retention of fluid in the dermis of the skin – myxedema An accumulation of mucopolysaccharides (glycosaminoglycans), such as hyaluronic acid and chondroitin sulfate, in the tissue causes many findings; most typical is the myxedema of the hands, feet, and face, which is often accompanied by a typical periorbital puffiness. Hypothyroidism during fetal development and childhood results in stunted growth and mental retardation – cretinism
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