1. Thyroid Metabolic Hormones Dr. Lara Samaan Owies
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. 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. Synthesis & Secretion of Thyroid Metabolic Hormones
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. Physiologic Anatomy of the Thyroid Gland.
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. Iodine The required ingested iodine is 50 milligrams each
year (1 mg/week).
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. Iodine trapping & T3 ,T4 Synthesis
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. T3 ,T4 Synthesis
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. 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. 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. Release of Thyroxine & Triiodothyronine from the
Thyroid Gland T4 &T3 are first cleaved from the thyroglobulin
molecule, then released as free hormones
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. Release of Thyroxine & Triiodothyronine from the
Thyroid Gland Proteases digest the thyroglobulin molecules and
release thyroxine and triiodothyronine in free form
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. 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. 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. 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. 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. 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. Physiologic Functions of the Thyroid Hormones
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. 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. 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. 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. 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. 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. 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. 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. Effects of Thyroid Hormone on Specific Bodily Mechanisms 5.
Increased basal metabolic rate increase the basal metabolic rate 60
to100 % above normal
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Regulation of Thyroid Hormone Secretion
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. 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. 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. 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. 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. Increased thyroid hormone in the body fluids decreases
secretion of TSH by the anterior pituitary.(direct effect)
54. Antithyroid Substances Drugs suppress thyroid secretion
thiocyanate, propylthiouracil, and high concentrations of inorganic
iodides.
55. Diseases of the Thyroid
56. Diseases of the Thyroid Hyperthyroidism Hypothyroidism
Cretinism
57. Hyperthyroidism
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. 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. 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. 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. Caused by: Edematous swelling of the retro-orbital tissues
and degenerative changes in the extraocular muscles.
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. Physiology of treatment of hyperthyroidism surgical removal
of most of the thyroid gland. Treatment of the Hyperplastic Thyroid
Gland with Radioactive Iodine
65. Hypothyroidism
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. 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. 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. 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. 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. 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. Myxedema Total lack of thyroid hormone function Bagginess
under the eyes Swelling of the face Nonpitting type edema
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. 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. 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. 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. Cretinism treatment iodine or thyroxine within a few weeks
after birth to avoid mental retardation
78. Cretinism
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. THE END Reference: textbook of medical physiology- guyton
& hall-chapter 76