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Thyroid disorders

Thyroid disorders. Examples of Genes Positively-regulated by T3.              1. Fatty acid synthetase      2. Growth hormone     3. Lysozyme silencer     4. Malic enzyme     5. Moloney leukemia virus enhancer     6. Myelin basic protein     7. Myosin heavy chain α    

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Thyroid disorders

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  1. Thyroid disorders

  2. Examples of Genes Positively-regulated by T3.              1. Fatty acid synthetase      2. Growth hormone     3. Lysozyme silencer     4. Malic enzyme     5. Moloney leukemia virus enhancer     6. Myelin basic protein     7. Myosin heavy chain α     8. Phosphoenolpyruvate carboxykinase     9. RC3   10. Spot 14 lipogenic enzyme   11. Type I 5′-deiodinase   12. Uncoupling protein Examples of Genes Negatively-regulated by T3.       1. Epidermal growth factor receptor      2. Myosin heavy chain β     3. Prolactin     4. Thyroid-stimulating hormone α     5. Thyroid-stimulating hormone β     6. Thyrotropin-releasing hormone     7. Type II 5’-deiodinase Non genomic effect

  3. T4, T3 iodine GIT kidney plasma thyroid oxidation T1, T2, T3, T4 TG cells T4 T3 D1,2,3 plasma T4, T3 TBG, TBPA, Alb liver

  4. Na/I symporter

  5. Thyreoglobulin NIS NIS Na/I symporter LE prelysosom RER endopl. ret. L lysosom G Golgiho ap. TPO thyroperoxidase TGN trans-Golgi network

  6. Jód • Wolff-Chaikoff effect – inhibition of TPO, H2O2 • NIS gen • mRNA TPO and Na/I symporter (NIS) • Inhibition of cascade cAMP • Ca2+-PIP2 • phospholipase C

  7. CD colloid droplet CV coated vesicle L lysosom PL phagolysosom EE early endosom

  8. Transport 0.03 % T 4 , a 0.3 % T 3 free thyroxine-binding globulin [TBG or thyropexin] 75% transthyretin [TTR or thyroxine-binding prealbumin (TBPA)], 20% albumin (HAS, human serum albumin) Buňka

  9. D1 liver, kidney, thyroid D2 brain, pituitary, muscles D3 brain, placenta, fetal tissue (HIF1)

  10. Control thyrostimulin

  11. Effects • growth • brain development (intelect) – neurogenesis, • migration, myelination, glial cells • ↑basal metabolism, ↑ metabolic turnover • ↑ oxygen consumption (↑ EPO secretion), ↑ temperature, UCP • ↑ proteosynthesis • ↑ proteolytic enzymes => prevalent proteolysis, muscles atrophy • ↑ glykogenolysis, ↑ glukoneogenesis↑ • ↑glykolysis => glycemia • ↑ lipolysis,↑ VLDL, LDL,cholestrol degradation, ↑ bile acids • excretion of bile acids • sensitivity to catecholamines • ↑ contractility (↑ systol. BP), ↑ heart rate (fibrilation), vasodilation • motility intest. , transport processes (diarrhea) • remodeling of bones and musles –catabolic effect osteoporosis, hypercalcemia, hypercalciuria (↓ TH = nanismus) • ↑ neuromuscular excitabilitytremor, muscle weakness

  12. Autoimmunity Antigens: TGB TSH receptor TPO NIS pendrin Antibodies TSI TSAb (stimulating) TSH blocking TSBII Cells T lymfo NK cells

  13. Hypofunction prevalence: 3 : 100 primary, Goitrogens: cassava, cabbage, kale, secondary cauliflower, turnip, terciary, mustard, and horseradish lack of nuclear TR Autoimmunity Antigens: thyreoglobulin, thyroperoxidase, TSH receptor Hashimoto´s thyroiditis preval. 2%, ↑ age, 4x ♀ than ♂ Myxedema (glycosaminoglycans) Basal metabolism, heat production CNS Cerebellar dysfunction (ataxia, nystagmus, dysdiadochokinesis, vertigo, tinitus) Deafness Mental activity Memory, depression

  14. Cardiovascular system contractility, CO peripheral resistance, diastol. pressure (termogenesis) sarcoplasmatic Ca pump, fosfolamdan myosin Na/K ATPase myxedem GIT achlorhydria anorexia constipation Blood anemia volume of plasma hypocoagulation Muscle weakness Development and maturation of brain

  15. Cretenism neurogenesis migration cortex hippocampus cerrebelum myelin

  16. Primary hypothyreosis – Hashimoto´s ttidis, radiation, sulphonamids fT4, TSH myxedema Central hypothalamus, pituitary no myxedema Subclinic – fT4, TSH Sy of low fT3 – starvation, cirrhosis, renal, heart failure T4 rT3 D3

  17. Hyperfunctionprevalence: ♀ 4 : 1000, ♂ 0.4 : 1000 • GRAVES-Basedow: aAb mimicking TSH a stimulating TSH receptor, ↓TSH, ↑T3, ↑T4, • TOXIC GOITER: iodine deficiency, • TOXIC ADENOMA: TSH receptor, • SUBCLINIC HYPERTHYREOSIS = ↓TSH, norm. T4, T3 • THYROTOXICOSIS FACTITIA: exogen. TH • SYNDROM IODIN-BASEDOW: • DE QUERVAINOVA SUBACUTE THYROIDITIS: viral, bacterial inflammation • OVERSECRETION OF TSH = norm. až ↑TSH, ↑T4 • EUTHYROID HYPERTHYREOXINEMIA = norm. TSH, ↑T4, (↑T3) • heart rate, orbitopathy, goiter, fatigue, sweating, dyspnea, weight loss, loss of muscle, apetite,

  18. goiter fatigue sweating, heat tolerance dyspnea weight loss, loss of muscle, apetite, orbitopathy exophtalmus (retrobulbar addipose tissue, edema of muscles) circulation heart (CO, rate) vasodilation heart failure muscles (degenerative changes) liver (necrosis)

  19. Thyroid and renal function hypothyreosis hyperthyreosis CO - + TPR + - RBF - + RAAS - + GFR - + Ability to concentrate - +

  20. Alzheimer: subclinic hyperfunction subclinic hypofunction familial AD high prevalence of autoimmune thyroid disease (ATD) oxidative stress Sclerosis multiplex: ATD 3-5x higher prevalence, thyroxin a myelination oxidative stress Parkinsonism: symptoms similar to hypothyreosis hyperthyreosis oxidative stress ?

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