1. 1. Thyroid Metabolic Hormones Dr. Lara Samaan Owies
2. 2. Lecture Outline Synthesis & secretion of Thyroid Metabolic Hormone Physiologic Functions of the Thyroid Hormones Regulation of Thyroid Hormone Secretion Diseases of the Thyroid
3. 3. Weighs 15-20 gram in adults Secrets thyroxine (T4) & triiodothyronine (T3) that increase metabolic rate of the body Thyroid secretion controlled by Thyroid Stimulating Hormone (TSH). Secretes calcitonin: important hormone for calcium metabolism
4. 4. Synthesis & Secretion of Thyroid Metabolic Hormones
5. 5. metabolically active hormones from thyroid gland: Thyroxine 93% Triiodothyronine7% The have the same function, but they differ in rapidity and intensity of action. Triiodothyronine is four times as potent as thyroxine, but it is present in blood in much smaller quantities and persists for a much shorter time than does thyroxine.
6. 6. Physiologic Anatomy of the Thyroid Gland.
7. 7. Physiologic Anatomy of the Thyroid Gland. Follicles, filled with a secretory substance called colloid and lined with cuboidal epithelial cells that secrete into the interior of the follicles. The major constituent of colloid is the large glycoprotein thyroglobulin. The thyroid gland has a blood flow about five times the weight of the gland each minute.
8. 8. Iodine The required ingested iodine is 50 milligrams each year (1 mg/week).
9. 9. Iodide Trapping Transported from blood through the basal membrane of the thyroid cell by iodide pump, this is called iodide trapping TSH concentration affects the rate of iodide trapping.
10. 10. Iodine trapping & T3 ,T4 Synthesis
11. 11. Synthesis of T3,T4 The E.R & G.A synthesize and secrete into the follicles a large glycoprotein molecule called thyroglobulin. thyroglobulin contains tyrosine amino acids, that combine with iodine to form the thyroid hormones( T4,T3) Thus, the thyroid hormones form within the thyroglobulin molecule
12. 12. T3 ,T4 Synthesis
13. 13. Synthesis of T3,T4 conversion of the iodide ions to an oxidized form of iodine o This oxidation is promoted by the enzyme peroxidase and its accompanying hydrogen peroxide. o When the peroxidase system is blocked or when it is hereditarily absent from the cells, the rate of formation of thyroid hormones falls to zero
14. 14. Synthesis of T3,T4 organification of the thyroglobulin o The binding of iodine with the thyroglobulin molecule is called organification o In the thyroid cells, however, the oxidized iodine is associated with an iodinase enzyme o the major product is thyroxine, then triiodothyronine (one fifteenth of the final product)
15. 15. Storage After synthesis o each thyroglobulin molecule contains up to 30 thyroxine molecules and a few triiodothyronine molecules in the follicle. o The amount stored sufficient to supply the body with its normal requirements of thyroid hormones for 2 to 3 months. o Therefore, when synthesis of thyroid hormone ceases, the physiologic effects of deficiency are not observed for several months.
16. 16. Release of Thyroxine & Triiodothyronine from the Thyroid Gland T4 &T3 are first cleaved from the thyroglobulin molecule, then released as free hormones
17. 17. Release of Thyroxine & Triiodothyronine from the Thyroid Gland pinocytic vesicles that enter the thyroid cell. Then lysosomes in the cell cytoplasm fuse with these vesicles to form digestive vesicles . .
18. 18. Release of Thyroxine & Triiodothyronine from the Thyroid Gland Proteases digest the thyroglobulin molecules and release thyroxine and triiodothyronine in free form
19. 19. Release of Thyroxine & Triiodothyronine from the Thyroid Gland These then diffuse through the base of the thyroid cell into the surrounding capillaries. Thus, the thyroid hormones are released into the blood.
20. 20. Release of Thyroxine & Triiodothyronine from the Thyroid GlandMonoiodothyronine & diiodothyronine during digestion are freed from thyroglobulin but are not secreted into the blood iodine is cleaved from them by a deiodinase enzyme this iodine available again for recycling within the gland for forming additional thyroid hormones. In the congenital absence of this deiodinase enzyme, many persons become iodine-deficient
21. 21. Daily Rate of Secretion of Thyroxine and Triiodothyronine. thyroxine 93% Triiodothyronine7% one half of the thyroxine is slowly deiodinated to form additional triiodothyronine Triiiodothyronine is mainly delivered to and used by tissues.
22. 22. Transport of T4 & T3 to Tissues Thyroxine and Triiodothyronine Are Bound to Plasma Proteins. 1. thyroxine-binding globulin 2. thyroxine-binding prealbumin and albumin
23. 23. Transport of T3 & T4 Tissues Thyroxine and Triiodothyronine Are Released Slowly to Tissue Cells. Half the thyroxine released to tissue cells about every 6 days. half the triiodothyronine released in1 day. Inside the cells they are stored and used over days/weeks
24. 24. no effect for 2 to 3 days (latent period) Once activity does begin, it reaches a maximum in 10 to 12 days,. it decreases with a half-life of about 15 days. Some of the activity persists for as long as 6 weeks to 2 months. The actions of triiodothyronine occur about four times as rapidly as those of thyroxine
25. 25. Physiologic Functions of the Thyroid Hormones
26. 26. The general effect of thyroid hormone is to activate nuclear transcription of large numbers of genes that result in generalized increase in functional activity throughout the body more than 90 % of the thyroid hormone molecules that bind with the receptors is triiodothyronine The thyroid hormone receptors are attached to the DNA
27. 27. On binding with thyroid hormone, the receptors become activated and initiate the transcription process. mRNA are formed Hundreds of new intracellular protiens are formed Most of the thyroid actions result from the enzymatic action of these protiens
28. 28. Thyroid Hormones Increase Cellular Metabolic Activity basal metabolic activity increases Mitochondria in most cells increase in size & in number Active transport of ions across cell membrane increases( Na-K ATPase enzyme, Na pump) that increases heat production
29. 29. Thyroid hormone affects growth This effect is mainly manifested in growing children promote growth and development of the brain during fetal life and for the first few years of postnatal life.
30. 30. Effects of Thyroid Hormone on Specific Bodily Mechanisms 1. Stimulation of carbohydrate metabolism 2. Stimulation of fat metabolism Increases lipid metabolism which decreases fat stores in the body & increases fatty acids concentration in plasma.
31. 31. Effects of Thyroid Hormone on Specific Bodily Mechanisms 3. Effect on plasma and liver fats increased thyroid hormone : decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, increases the free fatty acids
32. 32. Effects of Thyroid Hormone on Specific Bodily Mechanisms decreased thyroid secretion: greatly increases the plasma concentrations of cholesterol, phospholipids,and triglycerides almost always causes excessive deposition of fat in the liver as well. The large increase in circulating plasma cholesterol in prolonged hypothyroidism is often associated with severe atherosclerosis
33. 33. Effects of Thyroid Hormone on Specific Bodily Mechanisms 4. increased requirements for vitamins Thyroid hormone increases the quantities of many enzymes because vitamins are essential parts of some of the enzymes or coenzymes, thyroid hormone causes increased need for vitamins
34. 34. Effects of Thyroid Hormone on Specific Bodily Mechanisms 5. Increased basal metabolic rate increase the basal metabolic rate 60 to100 % above normal
35. 35. Effects of Thyroid Hormone on Specific Bodily Mechanisms 6. Decreased body weight Greatly increased thyroid hormone almost always decreases the body weight greatly decreased hormone almost always increases the body weight. these effects do not always occur, because thyroid hormone also increases the appetite, and this may counterbalance the change in the metabolic rate.
36. 36. Effects of Thyroid Hormone on Specific Bodily Mechanisms 7. Effect on cardiovascular system Increased Blood Flow and Cardiac Output. The rate of blood flow in the skin especially increases because of the increased need for heat elimination from the body) Increased heart rate clinicians uses HR in determining whether a patient has excessive or diminished thyroid hormone production.
37. 37. Effects of Thyroid Hormone on Specific Bodily Mechanisms Increase heart strength The increased enzymatic activity caused by increased thyroid hormone production apparently increases the strength of the heart when only a slight excess of thyroid hormone the heart muscle strength becomes depressed because of long-term excessive protein Catabolism in severely thyrotoxic patients. Normal Arterial Pressure.
38. 38. Effects of Thyroid Hormone on Specific Bodily Mechanisms 8. Increased respiration The increased rate of metabolism increases the utilization of oxygen and formation of carbon dioxide;
39. 39. Effects of Thyroid Hormone on Specific Bodily Mechanisms 9. Increased GIT motility increased appetite and food intake, Increases the rates of secretion of digestive juices and motility of GIT Hyperthyroidism often results in diarrhea. Lack of thyroid hormone can cause constipation.
40. 40. Effects of Thyroid Hormone on Specific Bodily Mechanisms 10. Excitatory effect on CNS In hyperthyroid individual extreme nervousness psychoneurotic tendencies, such as anxiety complexes, extreme worry, and paranoia.
41. 41. Effects of Thyroid Hormone on Specific Bodily Mechanisms 11. Effect on the function of muscles Slight increase in thyroid hormone usually makes the muscles react with vigor(strength) excessive hormone quantities, the muscles become weakened because of excess protein catabolism lack of thyroid hormone causes the muscles to become sluggish(slow movement), and they relax slowly after a contraction
42. 42. Effects of Thyroid Hormone on Specific Bodily Mechanisms One of the most characteristic signs of hyperthyroidism is a fine muscle tremor tremor can be observed easily by placing a sheet of paper on the extended fingers and noting the degree of vibration of the paper.
43. 43. Effects of Thyroid Hormone on Specific Bodily Mechanisms 12. Effect on sleep the hyperthyroid subject often: 1. has a feeling of constant tiredness. 2. difficult to sleep hypothyroidism : 1. extreme somnolence(sleepiness). 2. with sleep sometimes lasting 12 to 14 hours a day.
44. 44. Effects of Thyroid Hormone on Specific Bodily Mechanisms 13. Effect on other endocrine glands Increased thyroid hormone increases the rates of secretion of most other endocrine glands
45. 45. Effects of Thyroid Hormone on Specific Bodily Mechanisms 14. Effect on sexual function In men lack of thyroid hormone is likely to cause loss of libido great excesses of the hormone, however, sometimes cause impotence
46. 46. Effects of Thyroid Hormone on Specific Bodily Mechanisms In women Lack of thyroid hormone often causes menorrhagia (excessive) & polymenorrhea(frequent) menstrual bleeding may cause irregular periods and occasionally even amenorrhea greatly decreased libido. the hyperthyroid woman, Oligomenorrhea (greatly reduced bleeding) amenorrhea.
47. 47. Regulation of Thyroid Hormone Secretion
48. 48. 1. TSH increases thyroid scretion TSH, also known as thyrotropin, is an anterior pituitary hormone, a glycoprotein increases the secretion of thyroxine and triiodothyronine
49. 49. TSH increases thyroid secretion A. Increased proteolysis of the thyroglobulin (within 30 minutes ) B. Increased activity of the iodide pump C. Increased iodination of tyrosine D. Increased size and increased secretory activity of the thyroid cells E. Increased number of thyroid cells plus a change from cuboidal to columnar cells and much infolding of the thyroid epithelium into the follicles **Last 4 require days-weeks to deveope
50. 50. Effect of TSH on thyroid gland TSH binds a TSH receptors on the thyroid cell. This increases cAMP formation inside the cell. the cAMP acts as a second messenger that result in: 1. immediate increase in secretion of thyroid hormones 2. prolonged growth of the thyroid glandular tissue itself.
51. 51. The hypothalamic hormone, thyrotropin- releasing hormone (TRH),control TSH formation: 1. TRH is secreted by nerve endings in hypothalamus. 2. Then ,the TRH is transported to the anterior pituitary by way of the hypothalamichypophysial portal blood,
52. 52. One of the best-known stimuli for increasing the rate of TRH , & so increasing TSH secretion, is exposure to cold acute decrease in secretion of TSH result from Excitement and anxiety(affect the CNS).
53. 53. Increased thyroid hormone in the body fluids decreases secretion of TSH by the anterior pituitary.(direct effect)
54. 54. Antithyroid Substances Drugs suppress thyroid secretion thiocyanate, propylthiouracil, and high concentrations of inorganic iodides.
55. 55. Diseases of the Thyroid
56. 56. Diseases of the Thyroid Hyperthyroidism Hypothyroidism Cretinism
57. 57. Hyperthyroidism
58. 58. Causes of Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves Disease). thyroid gland increase 2-3 times normal size, tremendous hyperplasia thyroid hormone secretion 5-15 times normal. TSH plasma concentrations are less than normal thyroid-stimulating immunoglobulin (TSI) are found in blood.(autoimmune action against thyroid gland.
59. 59. Thyroid Adenoma a tumor that develops in the thyroid tissue and secretes large quantities of thyroid hormone. No autoimmune disease the remainder of normal thyroid tissue is totally inhibited because the thyroid hormone from the adenoma depresses the production of TSH.
60. 60. 1. a high state of excitability 2. intolerance to heat. 3. increased sweating. 4. mild to extreme weight loss (sometimes as much as 100 pounds), 5. varying degrees of diarrhea. 6. muscle weakness. 7. nervousness or other psychic disorders. 8. Extreme fatigue but inability to sleep. 9. tremor of the hands. Symptoms of Hyperthyroidism
61. 61. exophthalmos protrusion of the eyeballs in 1/3 of hyperthyroid patients Eyeball protrusion may damage vision eyelids do not close completely when person blinks or sleeps which results in dryness and infection, resulting in ulceration of the cornea. high concentrations of TSIs
62. 62. Caused by: Edematous swelling of the retro-orbital tissues and degenerative changes in the extraocular muscles.
63. 63. Diagnostic tests of hyperthyroidism Measuring free T4 (& sometimes T3) in the plasma, using radioimmunoassay. most accurate test Other tests: basal metabolic rate, TSH plasma concentration TSI concentration
64. 64. Physiology of treatment of hyperthyroidism surgical removal of most of the thyroid gland. Treatment of the Hyperplastic Thyroid Gland with Radioactive Iodine
65. 65. Hypothyroidism
66. 66. Hypothyroidism Initiated by autoimmunity destroys the gland rather than stimulates it. autoimmune thyroiditis. This results in fibrosis of the gland diminished secretion of thyroid hormone.
67. 67. Thyroid goiter Endemic Colloid Goiter Caused by Dietary Iodide Deficiency. iodineT3 &T4 TSH secretionthyroglobulin larger gland gland may increase to 10 to 20 times normal size. ***Goiter:greatly enlarged thyroid gland
68. 68. Thyroid Goiter Idiopathic Nontoxic Colloid Goiter. Mild thyroiditis slight hypothyroidism increased TSH & progressive growth of the noninflamed portions of the gland. This could explain why these glands usually are nodular, with some portions of the gland growing while other portions are being destroyed by thyroiditis.
69. 69. Thyroid Goiter In colloid goiter , abnormality in enzymes may happen Deficiency in: iodide-trapping mechanism peroxidase system coupling of iodinated tyrosines in thyroglobulin. deiodinase enzyme Goitrogenic substances found in turnips and cabbages
70. 70. Physiologic Characteristics of Hypothyroidism. fatigue and extreme somnolence with sleeping up to 12 to 14 hours a day extreme muscular sluggishness slowed heart rate decreased cardiac output decreased blood volume increased body weight
71. 71. Physiologic Characteristics of Hypothyroidism. constipation mental sluggishness, depressed growth of hair and scaliness of the skin, froglike husky voice, in severe cases, development of an edematous appearance throughout the body called myxedema
72. 72. Myxedema Total lack of thyroid hormone function Bagginess under the eyes Swelling of the face Nonpitting type edema
73. 73. Atherosclerosis in Hypothyroidism decreased fat and cholesterol metabolism and diminished liver excretion of cholesterol in the bile increase in blood cholesterol associated with increased atherosclerosis Particularly in myxedema Might lead to early death
74. 74. Diagnostic test & treatment Low Free thyroxine in blood Low basal metabolic rate Increased TSH Low TSH (when hypothyroidism results from depressed response of pituitary to TRH) Treatment: daily oral ingestion of thyroxine tablets
75. 75. Cretinism Caused by extreme hypothyroidism in early fetal life, infancy or childhood Failure of body growth &mental retardation congenital cretinism - congenital lack of hormone endemic cretinism - iodine lack in diet
76. 76. Cretinism A neonate may have normal appearance and function because it was supplied by thyroid hormone by the mother while in utero, few weeks after birth, the neonates movements become sluggish and both physical and mental growth begin to be greatly retarded.
77. 77. Cretinism treatment iodine or thyroxine within a few weeks after birth to avoid mental retardation
78. 78. Cretinism
79. 79. Cretinism Skeletal growth more inhibited than is soft tissue growth. the soft tissues enlargement gives an obese, short appearance. the tongue becomes large in relation to the skeletal growth that it obstructs swallowing and breathing, inducing a characteristic guttural breathing that
80. 80. THE END Reference: textbook of medical physiology- guyton & hall-chapter 76