1. 1 Chapter Ⅴ.The Thyroid PS Wang/ 2004.05

2. 2 W.F.Ganong:Review of Medical Physiology 2003 20th Ed. Fig.18-1 #147

3. 3 W.F. Ganong: Review of Medical Physiology 2003 20th Ed. Fig.18-2 #148

4. 4 The thyroid gland is the only tissue of the body which is able to accumulate iodine in great quantities and combine it into a hormone. The basic unit of the thyroid gland is the thyroid follicle which consists of a hollow sphere made up of a single layer of epithelial cells which enclose a colloid- filled space. PS Wang/2004.05

5. 5 M. E. Hadley: Endocrinology 2nd ed. 1988 fig.13.4 #2019

6. 6 T 3 or T 4 may be secreted directly into the criculation or stored in the follicle after combination with a protein to form thyroglobulin (a kind of glycoprotein with MW = 680,000) When needed, the thyroglobulin is hydrolyzed by a protease enzyme present in the follicular cells thereby freeing thyroxine into the blood stream PS Wang/2004.05

7. 7 Guyton & Hall : Textbook of Medical Physiology 10th ed.2000 fig.76-2 #364

8. 8 Function of Thyroid Cells 1.Thyroid cells collect and transport the iodine and synthesize the thyroglobulin, then secrete it into the colloid. 2.Remove the thyroid hormones from thyroglobulin and secrete them into the circulation. PS Wang/2004.05

9. 9 The steps in thyroid hormone biosynthesis are as follows: 1.I - trapping 2.I - oxidized to I 2 3.Iodination of tyrosine to mono-iodotyrosine (MIT) 4.Further iodination of MIT to di-iodotyrosine (DIT) 5.Condensation of 2 molecules of DIT to form thyroxin 6.(Possible) condensation of 1 molecule of MIT and 1 molecule of DIT to form tri-iodothyronine (T 3 or TRIT). A summary of these reactions is given in Figure 7-2. PS Wang/2004.05

10. 10 #144

11. 11 W.F. Ganong: Review of Medical Physiology 2003 20th Ed. #153 p329

12. 12 W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #150

13. 13 #1423

14. 14 F.S. Greenspan & D. G. Gardner : Basic &Clinical Endocrinology 7th ed.2004 p228 #1324

15. 15 W.F. Ganong: Review of Medical Physiology 2003 20th Ed. #1424

16. 16 W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #1425

17. 17 W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #152

18. 18 ItemT3T3 T4T4 No. of I34 Biosynthesis Biological Activity Half –Life Amount in Circulation Free Form in Circulation Binding Affinity with TBG MIT+DIT 4-5 1 day 0.35% 1% 1 DIT+DIT 1 1 week 99.6% 0.1% 10 PS Wang/2004.05

19. 19 J. Tepperman & H. M. Tepperman :Metabolic and Endocrine Physiology 5th ed.1987 p173 #1450

20. 20 M. E. Hadley: Endocrinology 2th ed. 1988 fig.13.10 #2021

21. 21 A classification of antithyroid drugs and substances can be made according to mode of action Inhibition of iodide trapping: Thiocyanates ( raw soybeans, cabbage) Perchlorates Inhibition of thyroxin synthesis (iodination) Thiouracil Propylthiouracil Methylthiouracil Thiourea Methimazole (Tapazole) Destruction of thyroid tissue: 131 I in large dosage Mode of action unknown : Iodides in much higher dosage than dietary requirements PS Wang/2004. 05

22. 22 J. Tepperman & H. M. Tepperman :Metabolic and Endocrine Physiology 5th ed.1987 p167 #145 24

23. 23 PBI = protein bound iodine. Determinations of blood levels of PBI have become a test of the amount of circulating T 4 or T 3. LATS = the long-acting thyroid stimulator, an abnormal immunoglobulin found in the plasma, may also cause a hyperthyroid state. PS Wang/2004.05

24. 24 LONG-ACTING THYROID STIMULATOR(LATS) Abnormonal factor in plasma of patients who have Graves’ disease. Protein; immunoactive against thyroid. Different from TSH; stimulates thyroid more slowly, acts longer. Cleared from blood more slowly than TSH. Crosses placental barrier; neonate may have symptoms of Graves’ disease. Symptoms of Graves’ disease. Produced by lymphocytes, not found in pituitary gland. May include group of 3 immunoglobulins. PS Wang/2004.05

25. 25 W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #154

26. 26 L.E. Mcdonald:Veterinary Endocrinology and Reproduction. 1976 2nd Ed. p54 #23

27. 27 Hypothyroidism Causes ---- (1) endemic colloid goiter: I 2 ↓ T 4 ↓ TSH↑ thyroglobulin (colloid) ↑ thyroid size ↑ (2) idiopathic nontoxic colloid goiter : goitrogen T 4 ↓(or normal) TSH↑ thyroid size ↑ Symptoms ---- sleeping 14-16 h/day muscular sluggish heart rate ↓ cardiac output ↓ mental sluggishness myxedema (↑mucopolysaccharides bagginess under the eyes & swelling of the face) arteriosclerosis cretinism PS Wang/2004. 05

28. 28 Diagnosis ---- (1) protein-bound iodine (PBI) ↓ (2) basal metabolic rate (BMR) ↓ (3) uptake of radioactive iodine ↓ Treatment---- (1) iodine (2) T 4 Hypothyroidism PS Wang/2004. 05

29. 29 Hyperthyrodism Causes ---- hyperplastic thyroid, size ↑ thyroid hormone secretion rate ↑ plasma ［ TSH ］ ↓ plasma ［ TSH ］ ↑ localized adenoma (tumor) Symptoms ---- intolerance to heat increased sweating weight loss diarrhea muscular weakness nervousness or the psychic disorders extreme fatigue but inability to sleep tremor of the hands exophthalmos ---- protrusion of the eyeballs PS Wang/2004. 05

30. 30 Diagnosis ---- (1) PBI↑ (2) BMR↑, 60% (3) uptake of 131 I ↑ Treatment ---- (1) Tx after administration of PTU (↓BMR) and high conc. of iodide (↓thyroid size & ↓ blood supply ) operative mortality < 0.1% (2) radiothyroidectomy by 131 I (> 5 mCi) Hyperthyrodism PS Wang/2004. 05

31. 31 Exophthalmos This occurs in 50% of patients and often precedes the development of obvious hyperthyroidism. A subpopulation of fibroblasts in the orbits ultimately develop into adipocytes, and these preadipocyte fibroblasts contain TSH receptor protein. The current theory of the development of exophthalmos is that when stimulated by the TSH receptor-stimulating antibodies in the circulation, these cells release cytokines that promote inflammation and edema. Ganong, W.F. Review of Medical Physiology 21st Edition, ©2003 by The Mc Graw-Hill Companies, Inc.

32. 32 Hashimoto’s Thyroiditis In Hashimoto’s thyroiditis, autoimmune antibodies destroy the thyroid with little if any stimulation, producing hypothyroidism. Ganong, W.F. Review of Medical Physiology 21st Edition, ©2003 by The Mc Graw-Hill Companies, Inc.