Before we begin the discussion of thyroid
pathology, let’s first take a look at normal
functioning and a review quickly of thyroid
HPT overview: hypothalamus, pituitary, thyroid
axis… the classic prototype physiologically
of your negative feedback mechanism.
Up until now, we’ve looked at one major
positive feedback mechanism and that was in
Here, with hypothalamus releasing TRH; please
do not forget that TRH is also responsible
for also releasing prolactin from the anterior
Now, we then land upon the anterior pituitary,
TSH will then bind to a very important receptor
on your thyroid gland known as your TSH receptor.
That becomes important to you pathologically
in Graves’ disease where type II hypersensitivity
type of thyroid stimulation immunoglobulin
is then going to bind to the TSH receptor.
We’ll talk further when we get into details
about thyroid hormone synthesis a very important
symport called your sodium iodide symport.
From your thyroid, you are then going to release
T4 in great quantity 20 to 1, 15 to 1 depends
as to whom you speak to, but point being is
T4 is released in much greater concentration
of ratio than T3.
And then all of the different organs that
your thyroid hormones then works upon it could
be the liver, it could be the intestine, it
could be the heart, it could be just about
everything and anything including your bones.
In this picture, you have two columns.
On the left, you have stimulatory and on the
right, inhibitory and as and when I can, I’ll
go ahead and start putting in clinical applications.
We begin with stimulation with alpha-adrenergic
agonists, the opposite of this would be alpha-adrenergic
Inhibitory… also keep in mind that you can
have nodules within this thyroid gland and
when you do remember that sometimes it could
be a space occupying lesion and therefore,
decreased release of your thyroid hormones
or really anywhere up and down your axis,
you could have a tumour that’s inhibiting
the release as space occupying lesion.
TRH, estrogen; inhibitory… somatostatin,
dopamine for the most part, think of it as
being or exhibiting inhibitory type of action
on your thyroid gland.
Dopamine, however, in terms of inhibitory
action would be with prolactin and perhaps
shares a little bit of inhibition with growth
Glucocorticoids, chronic illnesses… chronic
illnesses is very important for us.
How do you feel when you’re ill?
Not too energetic, maybe if there were symptoms
that you wanted to equate it to, it would
be more so along the lines of hypothyroidism.
We’ll talk a little bit more about chronic
TSH, TSH receptor, stimulating antibodies
is the full phrase there, Aby standing for
antibodies whereas inhibitory…
TSH receptor blocking antibodies and so, here,
if you’re thinking about, once again, some
type of autoimmune disease such as Hashimoto,
then keep in mind that at any point during
the thyroid hormone synthesis and release,
you could have destruction of thyroid hormone
We’ll talk more later.
Iodine could be both inhibitory or stimulatory,
keep that in mind.
The way that it could be stimulatory is that
if you required to synthesize thyroid hormone
then iodine obviously will be responsible
for the key element of creating a thyroid
hormone or if there was too much iodine, at
some point in time, you might have a negative
But, in both instances, keep in mind that
you may result in goiters… iodine deficiency
or iodine excess.
Lithium is a big one; lithium… two major
organs that lithium is responsible for causing
dysfunction and that you’re responsible
Number one, thyroid gland and number two,
down the kidneys will bring in about a nephrogenic
type of diabetes insipidus picture.
The thyroid gland itself and its histology.
What you’re seeing in the image is the middle
area that is homogenously eosinophilic and
pinkish then surrounded by a boundary of what’s
known as your follicular epithelial cells.
Now, what we’ll do further is and what you’ve
already done is take the follicular epithelial
cell and have your basolateral side facing
B basolateral, B blood… and then the apical
membrane which is then facing the colloid,
that homogenously pink region that is then
responsible for housing or storing your thyroid
Thyroid hormones are made in the follicular
epithelial cell, as we shall see, the key
element there being iodine; regulated by TSH.
Remember, every single thyroid tissue or cell
has a TSH receptor.
That TSH receptor will be incredibly important
for us to stimulate or initiate thyroid hormone
synthesis because it brings about sodium iodide
symport, as we shall see.
Serum T3 and T4 are then bound, once they
get into circulation.
Remember, these are lipid soluble, hmm?
Prior to this, they were water soluble.
What do I mean?
The TSH receptor on the thyroid gland… water
soluble IG protein type of signal transduction.
But, when the thyroid hormone gets into circulation,
you know darn well that its effects within
the nucleus in transcription/translation and
such is extremely, extremely critical and
So, therefore, it will pass through the membrane;
so, therefore, you-you need to make sure that
you’re able to regulate that.
And so, therefore, the liver then produces
what’s known as your binding globulin…
liver; not inside my thyroid gland right now.
What I’ll show you in a little bit is your
thyroglobulin and I’ve asked you a number
of times do not get the two confused and you
want to keep things… keep these separate
clinically, as you shall see.