So thyroid gland is located in the anterior neck and
it weights about 10 to 20g, probably the weight of
a pen.
And there are two lobes that's connected by the isthmus.
Thyroid gland is a highly vascular um, which is important
for their function because the thyroid hormones has many, many
important functions in virtually every type of cells in our
body.
Which is why once they're released, those hormones has to
be, um, transported into the, um, circulation where they can
reach their target tissues.
Um, thyroid, um, sort of thyroid glands are made of,
um, hollow follicles called the thyroid follicles.
So those thyroid follicles are lined by epithelial cells.
And these cells are called principal cells.
And these are the cells that are responsible for the
synthesis of thyroid hormones T3 and T4.
Um, thyroid follicles are filled with thyroid colloid, which is
where thyroid hormones are being stored before they get released
into the circulation.
You also have some C cells called clear cells.
And the reason for this is because under the staining
staining conditions, those cells don't actually get stained and hence
the name on clear cells.
So these are the follicular cells.
Those cells are responsible for the synthesis and the secretion
of calcium, which is really important in regulating calcium homeostasis.
We won't be sort of discussing the role of calcium,
but if you're interested in how they help to regulate
calcium homeostasis, um, there's loads of information on various textbooks
or online resources.
Um, feel free to have a look.
But today we're mainly focussed on the role of T3
and T4.
So fibroid hormones are, um, amino acid derived hormones.
Um, so they are structurally very similar to the amino
acid tyrosine.
Um, iodine is essential for the synthesis of thyroid hormones
because, um, iodine essentially has to be attached to the
tyrosine molecules to, to form T3 and T4.
And this is why, when there is a condition of
iodine deficiency, you could also have cases of hypothyroidism, which
is insufficient release of thyroid hormones.
And this is just because iodine is absolutely essential during
the synthesis of thyroid hormones.
So the way it works is the thyroid hormones are
generated from the donation and the coupling of tyrosine, the
amino acids tyrosine.
So if you have sort of three binding molecules being
sort of coupled to terracing, you will have tried iodine
patterning, which is T3.
And then if you have four iodine molecules on the
thyroid hormone you will have tetra ending therapy.
Hence Three four.
So the synthesis and secretion of thyroid hormones.
Uh, uh, sort of um, um, regulated, um, in, in
a way that, um, um, it actually explains why they're
so important.
So the principle cells, which is the epithelial cells that
makes the thyroid, um, follicles, um, making a sacred, um,
thyroid glowing and then sort of, um, dump them into
the colloid.
And then at the same time, iodide gets absorbed from
the blood into the follicle cells.
Um, iodide gets oxidised, um, at the sort of apical
membrane and then also gets released into the colloid, and
then it is in the colloid that ion then um,
Attached to the amino acids tyrosine.
And then they will form either mono ion, then tyrosine
MIT or die.
And the entire thing um det which then incorporated into
um thyroid globin, which is a process that's actually, um,
being regulated by an enzyme called thyroid peroxidase.
And then this is why, um, thyroid peroxidase actually has
a central role in the, in, in the synthesis and
regulation of thyroid hormones.
And then you will, you will see later on if
we have a defect in um, thyroid peroxidase, we will
actually have trouble, um, having sufficient the thyroid hormones being
being produced.
Um, once Mitt and the it are formed in the
Um, they will actually, um, sort of be, um, sort
of packed into the, into the, um, sort of combined
with lysosomes and then being exocytosis into the outside of
the, the colloid where they will get, um, sort of
released into the circulation in the form of T3 and
T4.
Um, once T3 and T4 are released into the circulation,
they actually most of them bind to carrier proteins and
it's only, um, only a very, very small proportion of
T3 and T4 don't actually bind to carrier proteins.
And then it is those small proportion of unbound T3
and T4 that are biologically active, um, T3 and T4,
although both can bind to bind to a thyroid hormone
receptors.
Um, T3 is a more potent form of thyroid hormones.
You can actually consider T4 as a pro sort of
hormone.
And it is produced by sort of the ordination of,
of T4.
Um, so most generally speaking, T3 is probably up to
ten times more active as compared to T4.
The receptors for thyroid hormones are found in the, um
nucleus, and they belong to a family of nuclear receptors.
So because of this, the general sort of role of
thyroid hormones is to actually interact with the, uh, nuclear
receptor, um, hormone, hormone receptors, where it actually regulates gene
transcription.
And the gene expression.
So the way it works is thyroid.
Thyroid hormones will actually bind to thyroid receptors.
And this is a sort of um a receptor that's
considered a new nuclear transcription factor, which means that they
regulate the gene transcription.
And then the binding of thyroid hormone to the thyroid
hormone receptor will actually trigger this cellular response.
There are two different types of isoforms of thyroid receptors
um thyroid receptor alpha and thyroid receptor beta.
And those receptors forms a sort of a complex with
another receptor called the retinoid X receptor, before they can
actually regulate gene transcription.
So the binding or forming of the thyroid receptor with
the retinoid X receptor complex can actually bind to to
what we call the thyroid response elements that are expressed
in genes that are responsible to, to to thyroid hormones.
And then once the thyroid receptor retinoid X receptor complex
activates these thyroid response elements, it will actually regulate gene
transcription.
In addition to this process, you also have a nuclear
receptor coagulation Co regulators, which either activates or suppress gene
expression.
But in general, because the thyroid hormone is a is
a transcription factor, it actually exerts its role in the
in the cells by regulating gene expression.
Um, as I mentioned many times today.
Thyroid hormones have have a profound effect in almost all,
sort of all of the organs in our body.
So in the central nervous system, the, um, sort of
expression of, uh, thyroid hormone receptors will actually be, um,
regulating gene expression that are responsible for the growth and
the development of the nervous system, which is why when
you have underactive or overactive thyroid glands, um, our central
nervous system gets affected.
Um, heart um, also responds to, to to to thyroid
hormones, which is why when you have overproduction or on
the production of thyroid hormones, you will have a sort
of changes in, um, heart rates and therefore changes in
blood pressure as well uh, thyroid hormones also, uh, plays
a role in the liver, where they, uh, they regulate
the gluconeogenesis, which is the sort of generation of glucose
from non carbohydrates, um, sort of substrate.
And also they play a role in the glycogen analysis.
And all of this is to actually, uh, increase the
availability of glucose, uh, to be used as a source
of energy.
Um, thyroid hormones also, um, act on the bones, muscles
and even blood cells to actually, uh, regulate their function,
um, by changes in, um, sort of gene expression and,
and the protein translation.
Um, how is thyroid hormone secretion regulated?
Um, well, this is actually under the control of a
negative feedback systems, and we call this system the hypothalamic
pituitary thyroid axis HPT axis.
So normally if you remember from our last lecture, um,
the thyroid dropping releasing hormone being produced in the hypothalamus
will actually, um, sort of act on the anterior pituitary
where it stimulates the secretion of the anterior pituitary hormone,
um, thyroid stimulating hormone, thyroid stimulating hormone.
Then, um, acts on the thyroid glands to stimulate the
release of thyroid hormones.
Once released into the circulation, thyroid hormones will feed back
to anterior pituitary and hypothalamus to switch off the the
secretion of trash and TSH.
Disorders related to thyroid glands are sort of either when
we have a.
Underactive thyroid glands where we don't have a sufficient thyroid
hormone being produced, or when we have an overactive thyroid
gland where we have too much thyroid hormone being produced,
and both of them can cause sort of pathological conditions
when we have not enough thyroid hormone being produced or
when we have a underactive thyroid glands, we call it
hypo thyroid ism and it can actually be acquired.
So if it's sort of it's a congenital, um, sort
of condition where, um, you just don't really have, um,
insufficient thyroid hormones.
And then this will actually cause, um, severe developmental abnormalities.
And because this is actually being sort of, um, tested,
um, from the, from the early stages of pregnancy, you
don't actually, um, say, um, thyroid failure.
Um, that, um, that often nowadays most of the hypothyroidism
is actually acquired, um, later in life.
So as I mentioned earlier, because iodine is so important
in the synthesis of thyroid hormones, um, and the condition
of iodine deficiency, uh, we just can't really, um, produce
sufficient amounts of thyroid hormones.
And this is actually used to be very common in,
um, Certain areas of the world.
Um, but it's less common as most of the countries
that sort of supplement the their, their salt and flour
with, with with sodium and light.
Um, another um, one of the most common form of
hypothyroidism is that that's acquired later in life is actually
caused by a autoimmune response.
And this this condition is also called a Hashimoto's thyroiditis.
Um, it is a condition that's very, very common in,
um, middle aged women.
Much, much more common than, than men.
Um, and the reason for this is, um, we, our
immune system started, um, generating autoantibodies against the thyroid peroxidase
or thyroid Globulin, both of which, as I said earlier,
is essential in the in the generation of or in
the synthesis of thyroid hormones.
And because of the production of those autoantibodies, our body
unable to produce a sufficient amount of thyroid hormones.
If you think about the way our thyroid hormones work
in various organs, you can actually sort of, um, understand
why certain symptoms associated with hypothyroidism occurs.
For example, um, bradycardia is is often seen in patients
with hypothyroidism.
And this is because, as I said earlier, um, thyroid
receptors is expressed in the heart.
And then they regulate the contractions of muscles.
Um.
Thyroid hormones also act on the thyroid hormone receptors in
the mitochondria, which is responsible for generating ATP.
And this is why when you have a hypothyroidism there,
such as, um, because of the decreased basal metabolic rate,
um, the patient will have a cold intolerance and they
will feel cold constantly.
And they will also have weight gain despite not, uh,
sort of, uh, eating more than what they normally do.
Thyroid hormones are also expressed in the central nervous system,
which is why when a patient with, uh, hypothyroidism can
actually have a slow mental processes.
And this is all because of the reduced stimulation of
the central nervous system.
Um, There are other conditions associated with hypothyroidism, such as
muscle wasting, hair loss, and fatigue.
And then this is all because the thyroid hormone is
a anabolic hormone.
It actually sort of a lack of thyroid hormones actually
cause all of these conditions.
Um, hypothyroidism is often associated with goitre, which is the
sort of growth of the, um, the cells in the,
in the thyroid glands.
And this is because when we have not when we
don't have a sufficient, uh, thyroid hormone being produced.
Um, remember, thyroid hormones are produced in response to, um,
thyroid stimulating hormone from the anterior pituitary.
And when we don't really have sufficient thyroid hormones being
produced, they cannot sort of provide sufficient negative feedback to
the anterior pituitary to switch off the production of thyroid
stimulating hormone.
And as a result of this, your anterior pituitary will
think, okay, there's no negative feedback being sent.
That means there's um, sort of um, that means the
body still needs to need more, um, thyroid hormone being
produced, and then it will continue to act on the
thyroid glands, um, by binding to the thyroid stimulating hormone
receptors.
Um, but because the, um, the, the thyroid glands cannot
generate T3 and T4, but at the same time, the
thyroid stimulating hormone keeps on activating the thyroid stimulating hormone
receptors.
It will actually sort of generate a response to thyroid
stimulating hormone.
Thyroid stimulating hormone actually is a tropical hormone.
It actually makes the cells to grow.
And because of this, it it actually allows the thyroid
cells to actually grow and form a goitre.
So if a patient is suspected of, um, hypothyroidism, mostly
um, Hashimoto's, uh, hypothyroidism thyroiditis, uh, simply because this is
the most common sort of form of hypothyroidism, um, a
blood test will be ordered and normally you will have,
um, the blood test result will actually show increased thyroid
stimulating hormone levels.
And this is because when you don't have T3 and
T4, um, to provide negative feedback to the hypothalamus, to
the, to the anterior pituitary, Um, the anterior pituitary will
continue to produce thyroid stimulating hormone, but because there's no
T3 and T4 being produced, you will have a very
low level or no levels of, um, of thyroid hormones.
Um, but because this is also a autoimmune disease, you
will be able to detect autoantibodies such as anti um
anti thyroid peroxidase antibody and anti thoroughgoing antibody depending on
what uh what actually triggered the the condition.
Um thyroid hormone is essential in lipid metabolism.
So when you don't have a sufficient amount of thyroid
hormone the um plasma levels of cholesterol will be increased.
So these are all the typical sort of results from
a blood test.
If someone has a, um, hypothyroidism, um, the treatment for
hypothyroidism or Hashimoto's thyroiditis is really to provide, um, replacement
thyroid hormones.
So those people will be having sort of, um, oral
supplementation of either T3 or T4.
Um, different patients respond to different treatments.
Um, and normally it is sort of a, um, the
it started with a relatively low dose and then slowly
increased.
And then it will have to be sort of the
the levels of the thyroid hormones will be sort of
more continuously monitored so that they can adjust the, the
dose of the, of the treatment.
Just the like high pass.
They were the hypothyroidism.
Um, which is the underactive thyroid gland.
You can also have an overactive thyroid gland, which causes
the condition called the hypothyroidism.
Most of the hypothyroidism actually occurs as a result of
autoimmune response.
And, um, this is sort of um, uh, because the,
the, the, um, your, your immune system generates antibodies that
actually, um, cause the thyroid to continuously sacred, uh, thyroid
hormones and the mostly the antibodies that are being generated,
um, are the ones that actually binds to the, um,
thyroid stimulating hormone receptors on the thyroid cells.
Um, so we know that society stimulating hormones are being
released from the anterior Pituitary to act on the thyroid
gland to trigger the release of thyroid hormones.
But then if you have a autoantibody that also can
bind to the thyroid stimulating hormone receptors.
So despite the sort of thyroid stimulating hormone secretion not
being affected, you can actually have a sort of force
signal that actually triggers the stimulation of thyroid hormones from
the thyroid glands.
And this will result in hyper secretion of thyroid hormones.
Um.
Once one of the most common form of hypothyroidism is
the is great disease.
And the sort of symptoms of graves disease is in
general, um, opposite To, um, Hashimoto's disease are simply because
it's, it's it's overproduction of, uh, thyroid hormones as opposed
to on the production of thyroid hormones.
So, um, as opposed to, to low basal metabolic rates
and the weight gain and cold intolerance, patients suffering from
high secretion of thyroid hormones will have very high basal
metabolic rates, and they will actually lose weight despite the
eating a lot.
And then they will also have, um, sort of heat
sensitivity.
So they're constantly feeling very warm.
Um, in terms of cardiac function, um, overproduction of thyroid
hormone will actually increase cardiac activity.
Um, and then also it has an impact on the
central nervous system to cause anxiety, tremor and, and other
Conditions.
Um, hypothyroidism, um, is often sort of treated depending on
um, um, sort of general, um, general conditions.
You can have um, sort of, uh, medications to inhibit
the thyroid peroxidase or to decrease the thyroid hormone synthesis.
So this will actually, um, prevents um, sort of hyper
secretion of thyroid hormones.
But then you can also have um, uh, sort of
medications to actually sort of prevent the conversion of T4
to T3.
So as I said, T4 is a precursor form of,
of thyroid hormones.
So if you actually stops the conversion of t T4
to T3, you also have um, sort of a reduction
of um, thyroid hormone secretion, but also probably the most
common treatment option would be to remove some of the
thyroid through surgery or radioactive iodine.
And this is because when we have iodine, it will
actually accumulate in the thyroid glands.
And then they will actually destroy some of the um
some of the thyroid glands of destroy some of the
cells that are responsible for secreting thyroid hormones.
And as a result of this, you will have the
sort of a correction of hypothyroidism.
However, this is a very, very sort of, um, difficult
condition in terms of, um, when, when you, when you
use surgery or radioactive iodine to try to sort of
reduce the some of the thyroid glands.
Um, it's often resulted in overtreatment, as in sort of
too much thyroid glands being removed.
And then this causes the opposite effect.
So you might be having the treatment for hypothyroidism but
ended up having hypothyroidism.
And one of the actually most famous case for this
was Oprah Winfrey.
She started of having symptoms of hypothyroidism, and as a
result of her treatment, she had um, she ended up
having hypothyroidism, which actually, uh, caused, um, caused her to
have the opposite effect.
But this is, I think, the, the clinical side of,
um, thyroid hormone or thyroid hormone related condition will be
covered in one of your lectures in the afternoon.
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