Let’s see diagnosis of adrenal insufficiency.
Begin at the very top, we’ll go through
kind of like what we did earlier with Cushing’s.
Speaking of which, be careful when you go
I would highly recommend that you quickly,
after our lecture here, go back and take a
look at the algorithm for Cushing’s please
because students always get these two algorithms
confused because there might be a little bit
of time delay before reviewing.
It’s important that you have these firmly
etched in your head, this is specific in algorithm
for adrenal insufficiency; there is no dexamethasone
suppression test, there’s no high dose/low
dose and such.
So, what are we looking at here?
Diagnosis of adrenal insufficiency can’t…
can be based on the following, excuse me,
can be based on the following.
Peak cortisol, obviously here it will be less.
Technically speaking, now, clinically be careful,
you might get a little bit of trouble because
how often are you going to find a research
committee that is…
I’m just being practical here.
How often can you find a research board or
committee who will give you permission to
then give your patient as much insulin as
you would like?
Do you know what I mean?
Because if you give too much insulin, you
might actually bring about a patient that
has hypoglycemia coma.
So, be careful.
But, for exam purposes, if you give insulin,
are you not creating stress?
Because now, you’ve created a hypoglycemic
As soon as you’ve created a fasting state,
what should you be releasing from the adrenals?
There you go, cortisol.
Do you understand that point now?
If your patient has adrenal insufficiency,
theoretically what you want to know here is
you give insulin, you’re not going to have
What if you diagnosed?
Oh, adrenal insufficiency.
How does that occur?
We don’t know yet, maybe it was the adrenal
gland primary, maybe it’s secondary, so
let’s keep going.
Contraindicated patients with coronary arterial
disease, seizure disorders or patients that
are older than 60, so really be practical,
take a look at the second bullet point.
If you find your patient to be older or they
have heart disease, you want to stay away
AM cortisol less than three micrograms, that’s
Now, once again, this comes make… this comes
to understand your diurnal rhythm of cortisol.
Before we move on, what’s the significance
of this bullet point?
We wake up in the morning, what does your
cortisol levels be?
It should be high.
Normally, physiologically, if you find your
cortisol levels to be low when you wake up
in the morning, then obviously this is adrenal
insufficiency and that technically less than
Random cortisol less than 18; examples hypotensive
ICU, patients with an albumin greater than
two and a half of grams per decilitre.
If diagnosed in ICU should retest adrenal
function status after recovery.
Those of you that are going to emergency medicine
will especially appreciate that little comment
there for ICU.
Peak cortisol less than 15 micrograms after
ACTH stimulation test.
So, here, we have an ACTH stimulation test,
but still you’re not having proper cortisol
What is this?
All this is used for laboratory testing for
This test is insensitive for diagnosis of
adrenal insufficiency shortly after pituitary
injury for obvious reasons… test is insensitive.
Metyrapone test… metyrapone test technically
means that you’re inhibiting 11-beta-hydroxylase
and so, therefore, if you block 11-beta-hydroxylase…
at least work through with this, can you picture
We’ve had this discussion before.
Metyrapone… let me ask you this, this you
should be able to understand.
If you block or inhibit 11-beta-hydroxylase
in your adrenal cortex, you’re not producing
If you’re not producing cortisol, then your
ACTH levels should be increased, right?
If you’re doing metyrapone testing and you’re
inhibiting 11-beta-hydroxylase and you don’t
find a rise in ACTH, what’s your diagnosis?
Secondary adrenal insufficiency.
Although ACTH response to metyrapone can, in theory,
distinguish between primary and secondary adrenal insufficiency,
such application of this test is not recommended.
Think about what I said, maybe perhaps first
Repeat what I just said about what this test
is actually inhibiting.
I said that after inhibiting the enzyme 11-beta-hydroxylase,
you still find depressed ACTH.
Diagnosis - secondary, secondary, secondary
Those are the type of patho-physiologic questions
that you’ll get on every single exam.
If adrenal insufficiency, low cortisol is
diagnosed based on any of the above test high
ACTH suggest primary adrenal insufficiency.
Adrenal imaging for next step of management,
you would then expect your adrenals to be
Low, inappropriate normal ACTH suggests secondary
Diagnosis… what’s your next step?
How or why is your cortisol decreased?
You find the ACTH to be high, most likely
it’s going to be atrophy of the adrenals.
Next step of management, CT image of the abdomen.
If you find your ACTH to be low, most likely
problem up in the pituitary.
In the algorithm here from top to bottom,
serum cortisol, my problem low, next step
If you find it to be high, it’s adrenal
If you find it to be low, it’s pituitary
Stop there, that should be your priority.
In the algorithm, you go as far as that and
you firmly imprint those bullet points.
Once you’ve understood that, clinically
speaking, as you move on from step one into
step two CK and step three in your boards,
then you have further issues.
You might get results that are equivocal.
What equivocal means is that it is non-confirmatory,
so you want to go a little bit further and
then you do ACTH stimulation test.
If you do an ACTH stimulation test and you
find low cortisol, then now you diagnose adrenal
You find ACTH stimulation test and you find
your cortisol levels to be high then you know
that you have normal adrenal.
If it’s still once again equivocal, you
come to this entire concept - if either metyrapone,
which is in the US not really used; it’s
more so in the-more so-more so in the United
Kingdom but nonetheless, it’s a fact that
it’s a-it’s a type of test that inhibits
11-beta-hydroxylase and insulin intolerance.
We talked about this being gold standard,
maybe perhaps you’re not releasing enough
Important algorithm, I’ve walked you through
the verbiage, let us now continue.
Here is, in fact, a metyrapone on your left
is perfectly normal… on your left is normal.
Where are you?
You’re in your adrenal cortex.
So, now you have pituitary, ACTH, you’re
in your adrenal, there’s your 11-deoxycortisol
and there’s the enzyme 11-beta-hydroxylase.
Metyrapone will work there to inhibit that
In a normal individual, normal on the left.
If you inhibit that enzyme, cortisol will
Take a look, ACTH is increased.
I want you to get into the pathology patient
on the right.
So, this is your patient with the disease,
At this point, all we know is that cortisol
All we know is that adrenal insufficiency
is taking place.
You give equivocal… you get equivocal results,
equivocal meaning it’s not confirmatory,
so you need to keep investigating, investigating.
Here, metyrapone inhibits 11-beta-hydroxylase,
you have decreased cortisol, but this time
take a look at ACTH, ha, it doesn’t rise.
Diagnosis - your patient on the right, his
or her diagnosis, is it primary or secondary
Secondary, secondary, secondary adrenal insufficiency.
Is there hyperpigmentation in this patient?
No because it is not Addison’s.
What is Addison’s?
Primary adrenal insufficiency.
Do you see the amount of patho-physiology
that’s involved in these conditions?
Treatment: first step, you have to give glucocorticoid.
You want to give mineralocorticoid replacement,
especially if it’s primary adrenal insufficiency.
Secondary, you have to give glucocorticoid.
Because in secondary, if you do not have ACTH,
your aldosterone levels should be relatively
normal, therefore your blood pressure is normal.
Usually lower doses than used in primary;
lowest dose of glucocorticoid improves patient’s
symptoms and should be used.