Chapter Ⅴ.The Thyroid
PS Wang/ 2004.05
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W.F.Ganong:Review of Medical Physiology 2003 20th Ed. Fig.18-1 #147
W.F. Ganong: Review of Medical Physiology 2003 20th Ed. Fig.18-2 #148
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• 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 colloidfilled space.
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PS Wang/2004.05
M. E. Hadley: Endocrinology 2nd ed. 1988 fig.13.4 #2019
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• T3 or T4 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
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PS Wang/2004.05
Guyton & Hall : Textbook of Medical Physiology 10th ed.2000 fig.76-2 #364
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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.
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PS Wang/2004.05
The steps in thyroid hormone
biosynthesis are as follows:
1. I- trapping
2. I- oxidized to I2
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
(T3 or TRIT). A summary of these reactions is
given in Figure 7-2.
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#144
W.F. Ganong: Review of Medical Physiology 2003 20th Ed. #153 p329
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W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #150
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#1423
F.S. Greenspan & D. G. Gardner : Basic &Clinical Endocrinology 7th ed.2004 p228 #1324
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W.F. Ganong: Review of Medical Physiology 2003 20th Ed. #1424
W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #1425
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W.F.Ganong: Review of Medical Physiology 2003 20th Ed. #152
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Item
T3
T4
No. of I
3
4
MIT+DIT
4-5
1 day
0.35%
1%
1
DIT+DIT
1
1 week
99.6%
0.1%
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Biosynthesis
Biological Activity
Half –Life
Amount in Circulation
Free Form in Circulation
Binding Affinity with TBG
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PS Wang/2004.05
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J. Tepperman & H. M. Tepperman :Metabolic and Endocrine Physiology 5th ed.1987 p173 #1450
M. E. Hadley: Endocrinology 2th ed. 1988 fig.13.10 #2021
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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:
131I in large dosage
• Mode of action unknown :
Iodides in much higher dosage than dietary requirements
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J. Tepperman & H. M. Tepperman :Metabolic and Endocrine Physiology 5th ed.1987 p167 #145
• PBI = protein bound iodine.
Determinations of blood levels of PBI have
become a test of the amount of circulating
T4 or T3.
• LATS = the long-acting thyroid stimulator,
an abnormal immunoglobulin found in the
plasma, may also cause a hyperthyroid
state.
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PS Wang/2004.05
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.
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PS Wang/2004.05
W.F.Ganong:
Review of Medical
Physiology 2003
20th Ed. #154
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L.E. Mcdonald:Veterinary Endocrinology and Reproduction. 1976 2nd Ed. p54 #23
Hypothyroidism
• Causes ---(1) endemic colloid goiter: I2↓
T4↓
TSH↑
thyroglobulin (colloid) ↑
thyroid size ↑
(2) idiopathic nontoxic colloid goiter : goitrogen
T4 ↓(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
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Hypothyroidism
• Diagnosis ---(1) protein-bound iodine (PBI) ↓
(2) basal metabolic rate (BMR) ↓
(3) uptake of radioactive iodine ↓
• Treatment---(1) iodine
(2) T4
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PS Wang/2004. 05
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
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Hyperthyrodism
• Diagnosis ---(1) PBI↑
(2) BMR↑, 60%
(3) uptake of 131I ↑
• Treatment ---(1) Tx after administration of PTU
(↓BMR) and high conc. of iodide
(↓thyroid size & ↓ blood supply )
operative mortality < 0.1%
(2) radiothyroidectomy by 131I
(> 5 mCi)
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PS Wang/2004. 05
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.
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Ganong, W.F. Review of Medical Physiology 21st Edition, ©2003 by The Mc Graw-Hill Companies, Inc.
Hashimoto’s Thyroiditis
In Hashimoto’s thyroiditis, autoimmune
antibodies destroy the thyroid with little if
any stimulation, producing hypothyroidism.
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Ganong, W.F. Review of Medical Physiology 21st Edition, ©2003 by The Mc Graw-Hill Companies, Inc.