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Title: the thyroid gland
Description: the function and mechanism of action of all the hormones
Description: the function and mechanism of action of all the hormones
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The thyroid gland
• The thyroid gland lies in front of the upper part of
the trachea just below the larynx
...
An occasional small pyramidal lobe is found on
the isthmus
...
• Each follicle is 50 - 500 µm in diameter and
lined by a single layer of cells
...
• Each follicle
is surrounded
by
a
dense network of fenestrated capillaries
...
• When the gland is active, the follicles are small,
contain small amount of colloid, and the follicular
cells
are
cuboidal
or
columnar
...
• The thyroid gland secretes three hormones; T4
(thyroxine - or tetraiodothyronine), T3
(triiodothyronine), and calcitonin
...
• The term “thyroid hormones” is often used to
refer toT4,T3
...
• The follicular cells also synthesize a high
molecular weight glycoprotein and secrete it
into the colloid
...
It
contains the tyrosine molecules which will be
iodinated and condensed into iodothyronines
as part of its molecule
...
• T3 and T4 are made in the thyroid follicles
through the following steps
...
Thyroglobulin synthesis
• 2
...
• 3
...
• 4
...
Condensation of two molecules of DIT to
form T4, or one molecule of D1T and one
molecule
of
MIT
to
form
T3
...
Oxidized to iodine (Io)
...
– Attachment of 1 iodine produces
monoiodotyrosine (MIT)
...
• Thyroid-stimulating hormone (TSH) of the
anterior pituitary stimulates all these steps
...
It is 4- 5 times as potent as T4
...
• It
is
called
the
reverse
T3
(RT3)
...
• However, most of the T3 in the plasma is derived
from deiodination of T4 by the tissues
...
• Lysosomal proteases break the peptide bonds
between the iodothyronines and throglobulin,
setting the T3 and T4 free
...
Transport of thyroid hormones
• The normal level of total T4 in plasma is 8µg/dL,
for T3 it is 0
...
• Only 0
...
2% of T3 are free, the
remaining portions are bound to plasma albumin,
thyroid-binding prealbumin (TBPA) and thyroidbinding globulin (TBG)
...
• Thyroid-binding proteins increase during
pregnancy, by estrogens, or tranquilizers (e
...
benzodiazepines)
...
• It is the free hormones which are effective, and
their levels are adjusted by feedback regulation,
regardless of the total hormone levels
...
• In this case the total plasma thyroid hormones
are increased, but the plasma free hormones
are normal and the case remains an
‘euthyroid’ case
...
• Accordingly, the following facts must be
remembered:
• A high or low levels of plasma thyroid-binding
proteins occur in normal euthyroid subjects
...
• In hyperalbuminemia, there is an increase in
plasma total thyroid hormones but the free
hormones are normal
...
• After exerting their actions, the thyroid hormones
are broken down to MIT and DIT, then to iodide
and tyrosine mostly in the liver, kidneys, and
skeletal muscles
...
• Some thyroid hormones are conjugated with
sulfates and glucuronates in the liver and secreted
with bile into the intestine from where it is lost in
stools
...
Calorigenic action:
• Thyroid hormones stimulate oxidative
metabolism in all tissues except the adult
brain, the testes, the uterus, the lymphatic
tissue, and the pituitary gland
...
• The metabolic rate, heat production, and 02
consumption increase
...
If food
intake does not supply the required energy, fats
and proteins of the tissues are catabolized and the
body loses weight
...
• They are important for conversion of carotenes to
vitamin A by the liver
...
• Milk secretion is stimulated by thyroid hormones
...
• 2
...
Afterwards, they are
important for growth through their permissive
action with growth hormone
...
Effect on the nervous system:
• Thyroid hormones are essential for normal
structural and functional development of the
nervous system in the first few years of life
...
• Deficiency of thyroid hormones early in life
produces permanent, irreversible retardation of
structural and fuuntional development of the
nervous system (cretinism)
...
Effect on the heart:
• Thyroid hormones stimulate the formation of
α-myosin heavy chains (-MHC) in the heart,
which is more powerful than the -MHC
...
• The hormones sensitize the heart to
catecholamines
...
Increased excitability of the
heart leads to frequent extra systoles
...
Synergism with catecholamines:
• Thyroid hormones increase the number and
sensitivity of -adrenergic receptors
...
g
...
• 6
...
• They decrease plasma cholesterol by
stimulating its uptake by the liver and its
excretion in bile
...
• Adequate thyroid hormones are essential for
gonadal functions
...
• TSH accelerates all the steps of synthesis and
release of the thyroid hormones
...
• In the absence of TSH, the thyroid gland shrinks
and atrophies
...
• Thyrotropin-releasing hormone (TRH) of the
hypothalamus stimulates the release of TSR
from the pituitary gland
...
• A rise in the free T3 and T4 inhibits the release
of the hypothalamic TRH and the pituitary
TSR, and a drop in T3 and T4 stimulates their
release
...
• Cold stimulates the release of the
hypothalamic TRH → release of pituitary
TSH→ secretion of thyroid hormones, but the
exposure to cold should be maintained for at
least 4 - 5 weeks
...
• These hormones are the human chorionic
gonadotropin (hCG) and the human chorionic
thyrotropin (hCT)
...
• These two hormones take over the control of
thyroid activity during pregnancy and TSH
secretion is markedly suppressed
...
• The thyroid enlarges by up to 50 % during
normal pregnancy (pregnancy goiter)
...
• Transient thyroid dysfunction is very common
in the months after delivery as the normal
control of the maternal thyroid is reestablished
...
Thiocyanate and perchlorate block the
iodine pump
...
Propylthiouracil and carbimazole block
the oxidation, of iodide to iodine, and prevent
the iodination of tyrosine
...
Excess iodide inhibit all the steps of thyroid
hormones synthesis and secretion
...
Its size is
decreased and its blood supply is markedly
reduced
...
• 4
...
g
...
They inhibit thyroid hormones
formation
...
But
consumption of large amounts of these vegetables
could lead to goiter (e
...
cabbage goiter)
...
• The manifestations of this defect depend on
the age of onset
...
• If it starts in an adult, it is called myxedema,
(a)- Cretinism
• Cretinism is a syndrome which results from
hypothyroidism in infancy and childhood
...
• There is little soft tissue growth more than
skeletal growth
...
• The accumulation of subcutaneous soft tissues
gives the patient an obese appearance
...
• Treatment of the patient with thyroxine at any
time restores the physical growth, but unless
the cretin is treated within a few weeks after
birth, mental retardation is irreversible
...
• It could be due to primary failure of the thyroid
gland (thyroid hypothyroidism), failure of the
pituitary to produce thyrotropin (pituitary
hypothyroidism), or, failure of the hypothalamus
to produce TRH (hypothalamic hypothyroidism)
...
• There is marked somnolence
...
• The appetite is decreased, but the patient
doesn’t
lose
weight
because
his
metabolic rate is reduced
...
• The hair is thin and scanty
...
• There is hypercholestrolemia which leads to
atherosclerosis
...
• In
these
cases, there is accumulation of proteins,
hyaluronic
acid
and
chondroitin
sulfuric acid in the skin which accumulate
water and make the characteristic jellylike
myxematous tissue
...
• These factors make the characteristic
appearance of myxedema skin which is buffy,
yellowish, dry, scaly with nonpitting edema
• Hypothalamic myxedema can be treated by
TRH preparations
...
• However, all cases of myxedema are
successfully treated by synthetic T4
preparations
...
• The most common form of hyperthyroidism is
Graves’ disease (exophthalmic goiter)
...
• The antibodies activate the TSH receptors and
stimulate the gland leading to hyperthyroidism
...
• The high plasma T4 and T3 levels suppress
TSH secretion by the anterior pituitary
...
• There are fine tremors of the outstretched
fingers
...
• Cutaneous vasodilatation makes the skin red
and warm, and excessive sweating makes it
moist
...
• Peripheral vasodilatation decreases the
diastolic pressure, so the pulse pressure
increases
...
• In fact, there could be weight loss due to the
high BMR
...
• There is exophthalmos (i
...
forward protrusion
of the eye ball)
...
• The swollen tissues push the eye-ball forward
Out of the limited room of the orbit
...
• If Graves’ disease is not treated, the TSH-R
[stim] Ab which initially simulate thyroid
follicular cells end up by destroying them
...
• Graves’ disease and exophthalmos respond
well to immunosuppressive drugs, e
...
glucocorticoids
Thyroid function tests
• 1
...
This is a specific reliable test
...
Estimation of plasma protein-bound
iodine (PBI)
...
• It is increased in hyper- and decreased in
hypothyroidism
...
• 3
...
• It is nonspecific test but generally an easy
useful indicator
...
Serum cholesterol:
• It is high in hypothyroidism and low in
hyperthyroidism
...
• 5
...
• The uptake of I23I in the thyroid area is high in
hyperthyroidism and low in hypothyroidism
...
• Radioactive
technetium,
given
as
pertechnetate, is now commonly used instead
of radioactive iodine as it is safer
...
• Goiter is classified into three types:
• 1
...
g
...
• 2
...
g
...
• 3
...
g
...
Title: the thyroid gland
Description: the function and mechanism of action of all the hormones
Description: the function and mechanism of action of all the hormones