Thyroid metabolic hormones

Thyroid Metabolic Hormones
Dr. Lara Sama’an Owies

Lecture Outline
 Synthesis & secretion of Thyroid
Metabolic Hormone
 Physiologic Functions of the Thyroid
Hormones
 Regulation of Thyroid Hormone
Secretion
 Diseases of the Thyroid

 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

Synthesis & Secretion of Thyroid
Metabolic Hormones

 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.

Physiologic Anatomy of the
Thyroid Gland.

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.

Iodine
 The required ingested iodine is 50
milligrams each year (1 mg/week).

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.

Iodine trapping & T3 ,T4
Synthesis

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

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

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)

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.

Release of Thyroxine &
Triiodothyronine from the Thyroid
Gland
T4 &T3 are first cleaved from the
thyroglobulin molecule, then released as free
hormones

Gland
 pinocytic vesicles
that enter the
thyroid cell. Then
lysosomes in the
cell cytoplasm fuse
with these vesicles
to form digestive
vesicles .
.

Gland
Proteases digest the thyroglobulin
molecules and release thyroxine and
triiodothyronine in free form

Gland These then diffuse through the base of the
thyroid cell into the surrounding capillaries.
Thus, the thyroid hormones are released
into the blood.

GlandMonoiodothyronine & 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

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.

Transport of T4 & T3 to Tissues
Thyroxine and Triiodothyronine Are
Bound to Plasma Proteins.
1. thyroxine-binding globulin
2. thyroxine-binding prealbumin and
albumin

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

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

Physiologic Functions of the
Thyroid Hormones

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

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

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

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.

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.

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

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

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

5. Increased basal metabolic rate
increase the basal metabolic rate 60
to100 % above normal

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.

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.

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.

8. Increased respiration
The increased rate of metabolism
increases the utilization of oxygen and
formation of carbon dioxide;

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.

10. Excitatory effect on CNS
In hyperthyroid individual
• extreme nervousness
• psychoneurotic tendencies, such as
anxiety complexes, extreme worry, and
paranoia.

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

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.

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.

13. Effect on other endocrine glands
Increased thyroid hormone increases
the rates of secretion of most other
endocrine glands

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

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.

Regulation of Thyroid Hormone
Secretion

1. TSH increases thyroid scretion
 TSH, also known as thyrotropin, is an
anterior pituitary hormone, a glycoprotein
 increases the secretion of thyroxine and
triiodothyronine

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

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.

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,

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).

Increased thyroid hormone in the
body fluids decreases secretion of
TSH by the anterior pituitary.(direct
effect)

Antithyroid Substances
• Drugs suppress thyroid secretion
• thiocyanate, propylthiouracil, and high
concentrations of inorganic iodides.

Diseases of the Thyroid
Hyperthyroidism
Hypothyroidism
Cretinism

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.

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.

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

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

 Caused by: Edematous swelling of the retro-orbital
tissues and degenerative changes in the extraocular
muscles.

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

Physiology of treatment of
hyperthyroidism
surgical removal of most of the
thyroid gland.
Treatment of the Hyperplastic Thyroid
Gland with Radioactive Iodine

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.

Thyroid goiter
Endemic Colloid Goiter
 Caused by Dietary Iodide Deficiency.
 ↓iodine↓T3 &T4↑ TSH
secretion↑thyroglobulin larger gland
 gland may increase to 10 to 20 times
normal size.
***Goiter:greatly enlarged thyroid gland

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.

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

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

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

Myxedema
Total lack of thyroid
hormone function
Bagginess under the
eyes
Swelling of the face
Nonpitting type edema

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

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

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

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 neonate’s
movements become sluggish and both
physical and mental growth begin to
be greatly retarded.

Cretinism treatment
iodine or thyroxine within a few
weeks after birth to avoid mental
retardation

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

THE END
Reference: textbook of medical physiology-
guyton & hall-chapter 76

Thyroid metabolic hormones

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