00:02
Let’s first take a look at our first spectrum
of pathology here with cortisol and this brings
us to, and I’m going to be very specific
here, this is Cushing’s syndrome.
00:14
What part of this is specific?
The syndrome versus disease.
00:20
Yes, there are two different diagnosis.
00:22
Well, by that I mean, the diagnosis is hypercortisolism
for both syndrome and disease, but then disease
and syndrome will tell you how cortisol is
being-being excessively created.
00:38
Who’s your patient with Cushing’s syndrome
in general?
Central obesity, because of that obesity,
you’ll notice the purple striae.
00:47
What’s striae mean?
Stretching of the skin.
00:50
You take a look at the face, looks like a
puffy moon facies, facial plethora; acne;
hirsutism.
01:02
Understand that Cushing syndrome, if it is
being developed as a pathology in the adrenal
cortex, would increase all of your adrenocortical
hormones.
01:13
Is that clear?
So, you will be increasing your aldosterone,
you will be increasing, as our topic refers
to cortisol, and also increases your androgen.
01:27
What’s hirsutism mean?
Hair-like or man-like hair distribution and
acne all part of increased androgen, right,
androgen production.
01:40
Cervico-dorsal fat accumulation, this is then
referred to… take a look at your patient
in the area by the trapezius on the neck region,
that’s your buffalo hump.
01:51
Easy bruising, thinned skin; muscle wasting
especially of the extremities.
01:58
You cannot ever miss a picture of a patient
that has excessive cortisol.
02:04
Welcome to hypercortisolism, here we have
Cushing’s syndrome.
02:07
Before we move on, you will be responsible
for four different places or four different
methods by which your patient is going to
increase cortisol levels.
02:19
The most common in the US, iatrogenic we’ll
talk about; number two maybe from the adrenal
cortex; number three from the anterior pituitary
producing too much ACTH and that would be
Cushing’s disease.
02:36
Paraneoplastically, in the chest, there’s
a lung cancer known as small cell lung cancer
that may result in ACTH thus cortisol… four.
02:46
If you’re not familiar with all four, not
to worry, we’ll go through all of them,
all I’m doing is laying down a foundation.
02:55
In addition with Cushing’s syndrome, I told
you earlier that not only would you have excess
cortisol, but you could have also excess aldosterone…
welcome to hypertension.
03:05
Because of excess cortisol, you are then going
to have insulin resistance thus diabetes,
osteoporosis, immunosuppression, talked to
you about lymphopenia.
03:19
There will be proximal weakness specific compared
with other signs and symptoms… proximal
weakness.
03:26
There will be abdominal striae due to that
central obesity.
03:30
Take a look at your patient here and psychological
symptoms may also be associated with Cushing’s.
03:38
Once again from head to toe, mental change
in hunger, hypertension… why the diabetes?
You have diabetes here because of?
Good, insulin resistance, glucose intolerance…
same language.
03:53
Why the hypokalemia?
Good, excess aldosterone.
03:59
How this isn’t Conn’s?
This is Cushing.
04:03
My point is in Cushing’s, you’re increasing
all adrenocortical hormones.
04:10
Easy bruising, thinning of the skin and striae;
thinning of the arms; you have your moon facies,
your buffalo hump, your cervicofacial area,
increased abdominal fat, trunk obesity, red
or purple striae, poor wound healing is a
big one and muscle wasting, osteoporosis.
04:32
With Cushing’s syndrome the causes… excess…
here we go now, we’ll go through the four.
04:40
Excess glucocorticoids especially cortisol,
how?
Iatrogenic… iatrogenic would be the most
common.
04:47
Now, I want to add a little bit more or at
least think…
I want you to think about a-a concept that
I’m going to offer here.
04:58
If you’re taking a hormone, if you’re
taking a hormone, then what does it do to
the releasing hormone or the hormone that’s
responsible for releasing it?
Tell me about the feedback mechanism, you’ll
see what I’m getting at.
05:13
Tell me about the feedback mechanism of cortisol.
05:17
Is it renin or is it ACTH?
It’s ACTH.
05:20
If you have excess cortisol and you’re giving
excess cortisol, what do you think happens
to your levels of ACTH?
It decreases.
05:35
Keep that in mind, I’m going to keep building
on them, building on them, building on them
because the language of that-language of that
is what the students get confused with.
05:45
Next, more language… slow down, think before
you move on.
05:50
ACTH independent, ah, how are you increasing
cortisol?
How are you increasing cortisol if it’s
ACTH independent?
Is it in the-Is it in the adrenal cortex,
is it in the anterior pituitary, is it in
the lung from small cell lung cancer or is
it iatrogenic, if it’s ACTH independent?
So, if it’s iatrogenic, that’s easy, all
that you’re looking for there is in a hospital
setting, the doctor might be giving your patient
cortisol… iatrogenic, so rule that out.
06:22
First and foremost, that’s the most common.
06:24
Is that clear?
Anytime you deal with Cushing’s on exam
or anytime a doctor asks you about Cushing’s,
you should be ruling out iatrogenic, number
one.
06:34
Now beyond that, let’s talk about in vivo,
in the body.
06:38
If it’s ACTH independent, how are you increasing
cortisol?
Good, adrenal cortex, it has to be because
if it was ACTH dependent then you might be
thinking about anterior pituitary.
06:53
This remind you would be called what?
Take a look at the very end here, we have
Cushing’s disease.
07:00
So, Cushing’s disease is specific for excess
cortisol due to excess ACTH coming from where?
What do you mean coming from where?
Coming from small cell lung cancer or anterior
pituitary?
Good, anterior pituitary.
07:16
Do you see how specific the term disease is?
What’s syndrome mean?
All syndrome means is hypercortisolism, but
you don’t know where it might be coming
from.
07:28
It could be-It could be one of the differentials.
07:31
Another ACTH dependent condition, the fourth
and final one here, and I’ll summarize them
again once we’re done, would be perhaps
paraneoplastic ectopically and we’re dealing
with a particular bronchogenic lung cancer
called small cell-small cell lung cancer;
not squamous cell, but small cell.
07:50
Find a way to memorize small cell/ACTH; ACTH
dependent/ Cushing’s syndrome.
08:01
Four different causes of hypercortisolism…
iatrogenic, ACTH independent, that’s cortisol
coming directly out of your adrenal cortex;
two, ACTH dependent, this being either from
the anterior pituitary or from small cell
lung cancer.
08:20
Now, we can move on.
08:23
Stepwise approach, what are you going to do?
First and foremost, exclude and rule out is
your patient somehow getting the cortisol
from exogenous use…
iatrogenic, factitious.
08:36
It all means the same thing.
08:38
Iatrogenic, factitious, exogenous all means
iatrogenic cortisol.
08:43
Know the language.
08:44
Next, we’re going to screen for endogenous.
08:48
In your head, three different places were
or three different methods, but you might
have hypercortisolism real quick… adrenals,
anterior pituitary, small cell lung cancer.
08:58
So, let’s screen for it.
09:01
Do not proceed with workup until… what do
you mean by biochemical?
Whenever that you can from henceforth on any
exam or in a hospital setting on the wards
or on the boards, you’ll be always-you’ll
be always trying to check for biochemical
test or biochemical diagnosis because it’s
cheap and it’s effective.
09:22
You don’t want to just order a CT every
single time, that is thousands of dollars
for you, well, for the hospital, maybe perhaps
for the patient and maybe your job, okay?
So, this is no joke.
09:34
What kind of biochemical hormone would you
be looking for?
ACTH.
09:40
Next thing that you want to do is keep separate
ACTH dependent causes and ACTH independent
causes of hypercortisolism.
09:50
Now, let’s move on.
09:55
Is there hypercortisolism, yes or no?
We’ll perform a screen test.
09:58
24 hour urine free cortisol, 1 milligram overnight
dexamethasone suppression test.
10:04
Let’s stop there and even to this day, you’re
still responsible to knowing the dexamethasone
suppression test because of its amazing concept.
10:14
And then I’ll give you a little bit more
information as we get to the end of this section
in which I’ll give you more current day
practice of what you, as a doctor, will be
doing in practice, okay?
But, let’s make sure that you get your questions
right so that you can get into practice.
10:30
We’ll begin.
10:32
Is there hypercortisolism?
Okay, now, close your eyes, think about that
diurnal pattern that I was telling you about
with cortisol.
10:39
When is cortisol the highest?
Oh, yeah, in the morning.
10:43
When is it the lowest?
At night.
10:45
Next, what’s my feedback mechanism for cortisol?
Is it renin or ACTH?
Good, ACTH.
10:53
You’re going to give dexamethasone from
now on, think of dexamethasone the same as
cortisol please, it’s analogous.
11:03
When are you giving this?
At night.
11:06
So, you’re going to give cortisol dexamethasone
at night.
11:11
Slow down here, work with me.
11:13
If you give cortisol at night, what are you
going to do with ACTH levels?
Feedback, you should, in a normal patient,
decrease your ACTH because you’re giving
dexamethasone at night.
11:28
So, wake up in the morning in a normal individual;
if you don’t have the ACTH, how much cortisol
are you going to have in the morning normally?
It should be decreased.
11:38
Hmm, so, now, you give dexamethasone at night,
you wake up in the morning.
11:43
Oh my goodness, you find your cortisol to
be elevated.
11:46
All that you know now about your patient is
hypercortisolism.
11:49
What did you already do before this?
Good, you’ve ruled out iatrogenic already,
you already ruled out iatrogenic.
11:56
Now, you know is that you have hypercortisolism,
three different possibilities.
12:01
So, what’s your next step?
Biochemical, biochemical, biochemical.
12:06
So, you’re thinking about ACTH, so it’s
either ACTH dependent or ACTH independent.
12:12
Let’s take a look at the algorithm here.
12:14
You take a look at your cortisol level.
12:16
We obviously will be dealing with the elevated
branch.
12:18
Let’s do an ACTH level, slow it down, think
through this.
12:24
Once you think through it, you’ll be going
through this quicker, trust me.
12:28
ACTH level, you find it to be decreased, you
find your ACTH levels to be decreased, then
where is this hypercortisolism coming from?
Good, it’s coming from your adrenals.
12:42
What’s your next step of management?
What’s your next step of management?
Imaging, maybe CT of the abdomen.
12:50
Not the chest, right?
Be careful.
12:53
They might put that, they might put CT of
the chest, they might put CT of the abdomen,
be smart.
12:58
If your ACTH is to be decreased, that means
that the hypercortisolism is being caused
by most likely a tumour in the adrenal cortex
producing cortisol independently.
13:07
So, this is ACTH independent.
13:10
What’s your next step of management?
Imaging of your abdomen to look for that adenoma.
13:17
Okay, so, now, we knocked out two… iatrogenic,
we just discussed ACTH independent.
13:25
We’re left with two more, what are they?
ACTH dependent.
13:30
Let’s go over to the right aspect of this
algorithm please and you find your ACTH to
be increased.
13:36
What are the two dependent differentials?
Maybe the anterior pituitary or maybe the
ectopic small cell lung cancer, right?
What are you going to do next?
So, where is the excess cortisol coming from?
Is it adrenal, is it pituitary, is it ectopic?
If you find decreased ACTH, then you’re
thinking about your imaging study and you’re
dealing with your adrenals.
14:02
If you’re dealing with ACTH, that’s increased,
there are two possibilities.
14:06
Now, you do a high dose dexamethasone suppression
list.
14:10
Do not, for your boards, worry about the dosage.
14:14
We have low dose and we have high dose.
14:17
So far, what kind of dose will you use?
Low, low, low and that I showed you was 1
milligram.
14:25
What about the high dose?
Well, the high dose, once again here, do not
worry about.
14:30
There are many theories out there as to how
it goes by suppressing this, but we’re going
to follow the same methodology that we did
earlier in the beginning of the algorithm.
14:39
So, let’s give high dose at night.
14:43
You give high dose at night, unbelievably
you wake up in the morning and you find your
cortisol levels to be low.
14:51
Oh wow, what’s your diagnosis?
Good, that’s Cushing’s disease.
14:57
So, for reasons that you must accept from
me right now is that high dose dexamethasone
suppression test will decrease the ACTH from
your pituitary, what’s your next step of
management?
Imaging, MRI of what?
The head.
15:13
What are you looking for?
An adenoma in the pituitary releasing ACTH.
15:19
This is secondary hypercortisolism.
15:21
Are you with me?
Lot of information here, it is most important
that you keep things organized.
15:28
If you feel yourself right now losing morale
and you’re feeling frustrated, pause me
for a second, go back from the top and go
through step by step by step of this algorithm
so you’re perfectly clear with the organization.
15:43
You do this a few times, you’ll be like
a record and you’ll be doing it automatically.
15:48
Let’s do another one.
15:50
So, we do high dose dexamethasone suppression
test, but this time you don’t suppress the
ACTH, you don’t.
15:55
What’s your next step of management?
Chest X-ray, okay?
Chest X-ray.
16:02
What are you looking for?
You’re looking for a primary nodule by the
mediastinum most likely being caused by small
cell lung cancer.
16:11
What’s your next step of management after
that?
That’s more-more of a step two CK, isn’t
it?
But, you already know, surgery.
16:20
There are a lot of questions that are coming
down from step two CK into step one.
16:23
So, next step of management is always important
for you.
16:26
So, is the excess cortisol ACTH dependent
or is it independent?
We already took care of-We already took care
of our independent.
16:35
Next, you perform a high dose and that particular
dosage is 8 milligrams overnight and we said
that if you find your ACTH to be depressed,
then your ACTH is coming from your anterior
pituitary Cushing’s disease.
16:49
Whereas if it’s not being suppressed, then
that ACTH is coming from your small cell lung
cancer, perhaps ectopically.
16:57
After confirmation of hypercortisolism, check
ACTH.
17:00
ACTH is suppressed, sources likely a cortisol
producing… please take a look and pay attention
to imaging… abdomen, CT/MRI.
17:10
If ACTH is normal or elevated, perform high
dose and we do high dose dexamethasone suppression
test and you find your cortisol to be depressed,
then you do your next step of management MRI
of the pituitary to find an adenoma there.
17:26
If you do not find cortisol suppression, then
you’re looking at and you perform a chest
X-ray... and this specifically... or a chest
CT and consider doing what’s known as an
octreotide scan.
17:40
And all of this may then help you diagnose
your patient with having small cell lung cancer
of the chest.