The topic is hypercortisolism, a very important
topic for us.
A very important topic because Prednisone,
a type of cortisol, is administered excessively
But, before we get into any of that though,
we will first take a look at the normal functioning
of your cortisol so that when we take a look
at the pathology, it will all come together.
The normal effects physiologically of cortisol
on metabolism as a stress hormone, we’ve
talked about this plenty, is to make sure
if one is in a state of fasting that cortisol
will do everything in the power to increase
the amount of glucose in circulation.
If it comes down to what is happening to uptake
of glucose by a tissue, understand that cortisol
decreases the uptake of glucose, thus [Inaudible
00:00:56] glucose in circulation.
If you are thinking about the balance in biochemistry
between glycolysis and gluconeogenesis, it
obviously will lean towards gluconeogenesis
resulting in more of a “hyperglycemic state”.
Next, cortisol, it permits for redistribution
of fat from the legs to the trunk.
Doesn’t it sound like an awful lot like
Cushing, which we will get into later on in
our discussion, where you have heard of trunk
obesity and you have heard of wasted extremities
Well, cortisol seems to-seems to do that on
a physiologic basis, visceral adiposity.
Cortisol causes bone demineralization.
In other words, it is going through a move,
your hydroxyapatite from the bone, bone reabsorption
resulting in excessively look for, once again,
long term corticosteroid use resulting in
Immunologically, cortisol has interesting
It could attenuate immune response.
Now, this is rather confusing to some, but
will bring clarity here, huh!
If it is cortisol and you are dealing with
acute inflammation, it causes demargination
of your neutrophils.
What does that mean?
Whenever there is cortisol administration,
you are not going to have cortisol staying
on the bench, it will come off the bench,
come into the circulation, thus may then cause
On the same token, cortisol and its effect
with lymphocytes would be apoptosis, so it
may actually bring about and it does lymphopenia.
So, the immunomodulation effects of cortisol
quite interesting, keep those separate.
As we know, cortisol could be used as an inflammatory,
thus used quite randomly and effectively for
Prednisone inhibiting phospholipase A2.
So, therefore, you are now going to have the
prostaglandin branch being created and so,
therefore, may then exert your anti-inflammatory
This picture here is referring to your diurnal
release of your cortisol.
What does that mean again?
It means that, as you wake up in the morning…
let’s take a look at your X axis and your
Your X axis represents days, the Y axis represents
concentration of cortisol.
What you are seeing here at the very top with
that orange curve at point 20, shall we say
approximately, the highest concentration of
cortisol, that would indicate when you first
wake up in the morning, as you go throughout
the entire day and let’s say that you get
to about, oh, 6-7 o’clock in the evening,
your levels of cortisol will decrease, this
Therefore, at the end of the day, your cortisol
levels are the lowest.
You go to sleep at night and as you do, this
is the area that you are seeing in dark shade
literally meaning night time and as you sleep
throughout the entire evening, you wake up
in the morning, you will notice please that
the cortisol level will then peak.
This fluctuation of cortisol during day and
night, day and night is known as your diurnal
type of pattern.
This becomes very important to us when we
go onto discuss our dexamethasone suppression
Once again, the point that you want to take
out of this, let me ask you, when is your
cortisol level the highest?
Good, in the morning.
Quickly, once again, this time, up until this
point, we have looked at cortisol synthesis.
Where is this cortisol synthesis taking place?
Be as specific as possible please.
Zona fasciculata of the adrenal cortex.
We have talked about how close [Inaudible
00:05:31] in there, we have talked about the
various enzymes in which that you require
so that you can form a cortisol.
Remember that when cortisol comes into circulation,
which is the blood, this time, what this picture
is showing us is now cortisol being delivered
to the target cell, okay, to the target cell;
example may be hepatocyte.
When cortisol enters circulation, remember
that it is a lipid soluble substance thus
requires a chaperone, a cortisol binding globulin.
The cortisol will then be released, it goes
into or passes through your membrane.
In the meantime, remember that the receptor
for cortisol is within your target cell, cytoplasm
to be exact, you have a heat-shock protein
that is now controlling the receptor.
But, once cortisol comes in, which is that
circle that you see here, the heat-shock protein
will be released, you have a receptor and
cortisol complex together will enter the nucleus,
as you see here.
If it is a hepatocyte then you should understand
that cortisol along with-along with glucagon,
as an example, may then bring about certain
DNA changes in transcription so that you then
create the necessary enzymes that are responsible
for gluconeogenesis just as an example and
cortisol, of course, express hormone.
Once you have reached the nucleus, you will
have transcription; mRNA being produced, translation
depending as to which protein is necessary
and that protein will then bring about a physiologic
response, in this case, we got to use an example
such as effective glucose being increased