I'm like, no, they're not really still like alive, so I'm gonna try to keep them
alive and we'll get to the other stuff.
Okay EMR?
and EMR's like, okay, I'll just remind you in five minutes
. Hi everyone, and welcome to another episode of EMPlify
I'm your host, Sam Ashoo.
Before we dive into this month's episode, I want to say thank you for joining us.
I sincerely hope that you find it to be helpful and informative for your
clinical practice, and I want to remind you that you can go to ebmedicine.net
where you will find our three journals, Emergency Medicine Practice, Pediatric
Emergency Medicine Practice, and Evidence Based Urgent Care, and a multitude of
other resources, like the EKG course, the laceration course, interactive
clinical pathways, just tons of information to support your practice
and help you in your patient care.
And now, let's jump into this month's episode.
All right, ladies and gentlemen, welcome back to another episode of EMPlify.
I am one of your hosts, Sam Ashoo, and on the other end of
the microphone joining me today.
TR Eckler, back feeling salty, but a little sweet.
That's, that's so apropos because today we are reviewing the Emergency
Medicine Practice article from October 2025, Emergency Department
Evaluation and Management of Patients With Adrenal Insufficiency.
You ever seen one of these patients in the ED?
A few, not many.
Now I will tell you this is what I took away from this article, is that the ones
that know they have it are very smart and will tell you exactly what they need
and are generally very well educated.
And then now I think there's more people that are on so many
different kinds of steroids.
You're seeing those humans creep into the emergency department and they
creep in with sepsis or they creep in with, you know, a nasty viral infection
and they're a little hypotensive.
And I think now I'm more worried about this overlap between infection and chronic
steroid use driving more of these patients my way and I need to be a little quicker
on the gun with steroids for these people.
If I'm gonna sling antibiotics at everybody for sepsis, I think
I'm a little closer to slinging a little bit of a hydrocortisone or
Solu-Medrol at everybody as well.
'Cause I think I'm gonna get more hits than misses there.
Yeah, I am fortunate or unfortunate enough, I'm not really sure which way this
goes, but to have seen someone go from like death's door to awake and totally
normal after a dose of hydrocortisone.
Like going from, hey critical care team, I need you to come down now.
We're starting pressors.
This person doesn't look good, isn't responding to fluids, and I'm
gonna need to hand off pretty soon.
And then they show up and they're like, hey, person looks like a rose.
What are you, what are you panicked about?
And I'm like, well, 30 minutes ago it didn't look like this.
If data serves, in a few hours, they'll do this again, so you should probably
be the one to catch them before that.
They're gonna need some repeat dosing.
But this is a, once again, fantastic article.
This one was authored by the Simcoes, a husband and wife team who did
an outstanding job reviewing all things adrenal insufficiency and
adrenal crisis with, as always, an evidence-based literature search.
And I think it was very good actually, of them to point out that there isn't
all that much great literature when it comes to adrenal insufficiency and
adrenal crises and that randomized control trials are mostly unethical
when we talk about, you know, do we withhold certain lifesaving medications?
But there are some advancements coming down the pipeline with
medications, I hope, and we'll get to all of that here pretty soon.
I did, as always, look at the introductory epidemiology information,
and I'm always taken back by like the frequency of these things.
Adrenal insufficiency is still considered a rare condition, like 200,000 people
in the United States with an estimated 20,000 adrenal crises events per year.
That's not really a small number in the country.
And there was a study in 2010, said 67% of patients with adrenal insufficiency
had consulted at least three physicians before getting the diagnosis, and
20% had suffered symptoms for five years before getting the diagnosis.
So this is definitely something that is a chronic illness and is
really a diagnostic challenge.
And hopefully after today's discussion, everybody listening
will understand why as well
I try to put numbers like these in context just a little bit 'cause I actually
thought that number was a little bit low.
But this is one of those kind of fun ones where I like to stop for a second and
be like, how many emergency departments are there in the United States?
So like, estimates are between five and 6,000.
So this means that somewhere around like four times a year, you're gonna see a
patient like this roll into your ER.
Now that's gonna vary by size and all kinds of stuff, but I like to go into
every shift with the idea being like, Hey, there's one zebra coming in today, and
if you stay sharp, you're gonna catch it.
Not every viral URI that's hypotensive and every gastroenteritis that's hypotensive
has got this adrenal crisis, but every now and again, one of these is gonna try to
sneak in and I kind of like that you know, it's a seasonal catch, not a daily catch.
Yeah.
100 percent true.
You're absolutely right.
It's not an insignificant number.
And again, if you are smart enough after hearing this and reading this article and
studying and taking the CME test to pick this up, I think you do your colleagues
and especially the patient, a huge favor.
The foundation for adrenal insufficiency and adrenal crises really
starts with the physiology of it.
And this kinda hearkens back to medical school and what we
learned as primary, secondary, and tertiary adrenal insufficiency.
And you know, I'm not sure I was that awake when I heard this the first
time around, but there is a fantastic illustration, figure one, which shows
you the brain, the hypothalamus, the pituitary gland and the adrenal glands
and describes in very simple detail why this is a problem and how it works.
And I kind of wish I'd had this figure when I was in medical school.
Honestly.
There are three locations involved in adrenal insufficiency, right?
There's the adrenal glands, which sit right above the kidneys.
There's the pituitary gland, which sits at the base of the brain, and then there's
the hypothalamus, and any one of those three can be problematic, and depending on
where the problem is, you get a diagnosis of primary, if it's at the adrenal glands,
secondary, if it's at the pituitary and tertiary adrenal insufficiency if it's
at the hypothalamus further up in the brain and the causes for those can vary.
So primary is actually the least common of the three and is typically autoimmune.
It can be congenital, so you can be born with that condition.
You can have congenital adrenal hyperplasia in children, or you can
develop Addison's disease as an adult.
But it can also be associated with infections like tuberculosis.
So especially in the developing world where tuberculosis is still rampant
this is a more common occurrence.
Secondary adrenal insufficiency is sort of in the middle and is
caused by a disruption of this hypothalamic pituitary adrenal axis.
So it's disrupting the signals between all three of these areas by
affecting the pituitary gland, and it's most commonly due to pituitary
tumors or trauma or radiation.
Which kind of makes sense.
And then the tertiary, the one that's highest up in the brain
adrenal insufficiency is caused by typically glucocorticoids from
all the steroids we give people.
So if you haven't heard that word of caution, go back one episode and
listen to my conversation with my guest just a couple of weeks ago about the
problems that occur from even short term steroid use, and you'll understand why
we prescribe so many of these things, why they're causing such problems.
So that's tertiary adrenal insufficiency and the foundational physiology for all of
this comes together when you think about the adrenal gland as having three layers.
Zone one or layer one has to do with the mineralocorticoid, aldosterone.
Zone two has to do with the glucocorticoid, cortisol.
And zone three is responsible for all of the androgens and in the crises and
the insufficiency we're going to be talking about today, we're discussing
the problems of insufficient aldosterone and cortisol, or zone one and zone
two, and so once you understand that physiology, you can refer back to
things like this table and this figure.
And even later on when we talk about labs and we talk about all the different
labs you need to order, you can discern which one of these three types they have
and then focus the treatment correctly, which is often a diagnosis made outside
the emergency department, honestly, because we're just recognizing the shock
or the adrenal crisis and treating it.
And then as we move to the inpatient realm, all that testing we've ordered
comes back and somebody much smarter than me is putting it all together
and making that formal diagnosis and telling you where the issue is.
Yeah, I, I think as you said, that figure is such a great summary of this,
and I think it really helps distill it to like where exactly the problem is.
I liked how I remembered this on a whiteboard in medical school,
and I remember the idea being that primary is the lowest.
It's at the level of the kidneys.
And then as you move up higher through the body up towards the brain, that's
secondary and tertiary and that follows with like where the problem is.
So if your cortisol levels only are low, that's primary.
When you start seeing low ACTH levels, that's secondary.
And then when all your levels are low, your corticotropin-releasing
hormone, your ACTH, and your cortisol, that's coming from your hypothalamus.
So I like how the levels point to where the problem is as you
go kind of more vertically.
It's a great figure and something you really need to review every now and
then because it does get confusing if you're not looking at this every day,
you may remember that you have to send these labs, but you may not recall
exactly what it is that it all means.
And the mainstay of treatment, and we will harp on this thousands of
times during this podcast today, but the mainstay of treatment for
adrenal crisis is administering corticosteroids that have both the
glucocorticoid and the mineralocorticoid effects, which is hydrocortisone.
So, you're gonna hear this a million times, but the treatment,
the emergent treatment for adrenal crisis is dosing hydrocortisone
without waiting for anything else, especially if you're suspicion's high.
And because it's been a while, we're gonna bring back trivia with TR
and start with our first question.
Surprise.
I didn't actually warn him ahead of time.
This is completely spontaneous for him.
Anyway.
. Awesome
. Question number one, etiologies of adrenal insufficiency.
Which of the following is the most common cause of tertiary adrenal insufficiency.
Now, before we jump into the answers, tertiary is up at the hypothalamus.
Which of these is the most common cause of adrenal insufficiency
up at the hypothalamus?
A, autoimmune B, chronic corticosteroid use.
C, pituitary apoplexy.
D, tuberculosis, or E, Waterhouse-Friderichsen syndrome.
So despite my love for tuberculosis and the recently released book,
Everything is Tuberculosis, which I strongly recommend everyone to read,
and my love for Waterhouse-Friderichsen syndrome because anytime you can tie
adrenal hemorrhages to meningitis and make that diagnosis, it's awesome.
But I know that this is chronic corticosteroid use because it's just so
rampant and something now that I'm much more aware of with my steroid prescribing.
There you go.
Tertiary adrenal insufficiency is the most common cause of adrenal
insufficiency and it's caused most often by exogenous glucocorticoids.
Well done, sir. Well done.
All right.
Let's step out of the pathophysiology section for just a moment and dive
into the differential diagnosis.
Now, this is exceptionally challenging, I think, because adrenal crises are
precipitated by diseases, infections primarily, and the presentation
of adrenal crisis has significant overlap in symptoms with many of
the diseases that cause the crisis.
So it's quite easy for us in the emergency department to get distracted
or maybe to stop once we've diagnosed the precipitating disease and not take
the extra step of figuring out, oh, they're also adrenally insufficient,
and now in an adrenal crisis.
And that overlap and that lack of moving to that extra step is where
the increased mortality comes.
So there is once again, a fantastic table on page six if you have access
to the article, which lists the differential diagnosis for adrenal
insufficiency and not surprisingly, it includes a bunch of things, infections
being at the top of the list, like chronic or long-term infections.
Things like HIV, tuberculosis, Lyme disease, long COVID, and hepatitis.
But there are other things as well, autoimmune diseases, diabetes,
malignancy, endocrinopathies like hypothyroidism, hyperthyroidism and
hyperparathyroidism, psychiatric disease, depression, anxiety, eating disorders,
renal insufficiency, both chronic and acute, cardiac disease like congestive
heart failure and cardiomyopathies, and gastrointestinal disease like chronic
liver disease and celiac disease.
All of these are included in the differential diagnosis for adrenal
insufficiency, but can also be precipitating adrenal crises.
And I thought the authors actually did a pretty good job of perusing the
literature for case reports and noting that relatively rare conditions, things
like tricyclic antidepressant overdoses, and takotsubo cardiomyopathies and
shock from anorexia have been diagnosed in the setting of adrenal crises.
And those diagnoses were mistakenly settled upon in cases where the patient
was actually suffering an adrenal crisis.
Just further demonstrating the overlap between all of these
multiple disease processes and the challenge in making that diagnosis.
So the take home message here being as you're entertaining multiple
diagnoses, and especially as you entertain some of the rarer causes,
don't forget about adrenal insufficiency and think about crisis presenting as
the cluster of symptoms that you're seeing in front of you right now.
All right, let's move on to pre-hospital care.
As always, our pre-hospital colleagues may be listening and do an outstanding job.
And this is, again, one of those challenging areas.
How is it that someone in the pre-hospital setting is going to come up with this
diagnosis when we even can't do it in the emergency department quite often?
And the answer is in ways that you probably already understand.
So looking for things like, are they wearing a medical alert bracelet
or do they have a necklace that says, Hey, I have this condition.
Do they have a pill box to be dosed in emergencies?
Did they mention that they're on medications like hydrocortisone and that
they've been taking their stress dose?
All of these are important factors that may come from the
patient or from family members.
If it's a child, this may come from the parent.
They may say, hey, yeah, they've been ill for three or four days and
we've been giving this stress dose steroids, but now we're having problems.
And so all of these are little historical pieces that our EMS colleagues can
extract from family members or people at the scene or hopefully from the patient.
And if the patient has an emergency kit with extra pills in it, that's helpful
to bring along so we can identify those.
There was one questionnaire cited in the article of 150 patients with chronic
adrenal insufficiency and found that 59 of them had adrenal emergencies.
So about a third of them experienced an adrenal crisis.
85% of those were already on their stress dose steroids, so they may be
able to tell you, hey, I've been sick.
And I've been on my steroids and I've been at the higher dose
and I'm still having problems.
And so that's an important piece of history to elicit
from the patient at the scene.
And there is a foundation called the CARES Foundation which has drawn attention
to the fact that many emergency medical services crews don't carry hydrocortisone.
It's not something that's typically carried on an ambulance.
And there's usually not a protocol for administering it pre-hospital.
And, you know, if it's a two minute drive to the hospital, maybe not a big deal.
But especially if you're out in a rural setting and you're gonna be taking
this person on an ambulance ride for an hour, that's a critical time where
you may be starting an IV, doing IV fluids, noticing that their shock is
getting worse and they're not responding.
And so this becomes a really important piece of history to obtain and a really
important medication to have on the truck.
Or to make sure if you don't have it on the truck that you see if they've
got it and you consider whether or not you wanna call med control and
give them their dose before they go.
If for some reason they can't give it or they were afraid
to or something like that.
There's always those things.
I think to your point, the biggest value I get from EMS on a daily basis
is when they come in and tell me, Hey, these are their medications.
This is the bag of their medications.
And they said they've stopped this or they haven't been able to take this, or
they just got an injection here in their back or in their knee or somewhere else.
And now I've really, from this article taken like how are the
steroids getting into your body?
Like are they inhaled?
Are they nasal?
Are they injections?
Are they oral?
Is there now a new combination that you weren't on before?
And then did you stop something that precipitated this?
And I think that's always gonna be something that EMS is gonna tip that to
you, and really save your posterior if you just listen hard enough to what's new and
what's actually getting taken versus not.
I'm a big proponent of EMS presentations directly to the clinician, so you know, to
the nurse practitioner, PA, or physician who's at the bedside at the time that
they're there because oftentimes this stuff can get lost in translation.
You know, they may give this to the nursing report.
They may give it to a tech and say, well, it's in my report,
which will be faxed later.
Or you may or may not get it in your EMR.
This is a critical piece of information that should not be
lost in that communication gap.
Which brings me to our second question in trivia with TR.
Prehospital management.
What the main limitation in prehospital care for adrenal
crisis in the United States?
So, which one of these is the biggest stumbling block in the US?
A, no diagnostic criteria available.
B, EMS cannot legally administer hydrocortisone in some states.
C, parents are unable to recognize symptoms.
D, cortisol levels are too unstable, or E, hydrocortisone causes allergic reactions.
All right, one more time.
Yeah, I feel like C,D, and E I'm okay, but what was A and B?
A was no diagnostic criteria available.
B was EMS cannot legally administer hydrocortisone in some states.
C was the parents can't recognize symptoms.
D was cortisol levels are too unstable, and E was hydrocortisone
causes allergic reactions.
Yeah, that's wild that there are some states that don't allow EMS
crews to administer hydrocortisone, and this interests me, as an area
for advocacy, like, this would not be so different than, you know, an
EpiPen, being able to administer an EpiPen if it's there, you know,
It is crazy, but the article actually does say yes in the United States, some states
don't allow EMS personnel to administer hydrocortisone from the patient's own
emergency kit, so they can't administer it, but they may be able to open the
kit and put the pills in their hand and say, hey, I'm just gonna help you.
Here are the pills.
It's very strange that such a law would exist for a lifesaving
medication like hydrocortisone.
But indeed that is one of the stumbling blocks in the United States.
A little bizarre, but absolutely true.
All right, let's get to the ED evaluation.
When they arrive in the emergency department, you want to recognize
the cluster of symptoms and prioritize these patients.
And in general, if they're in an adrenal crisis, they're gonna be presenting
with something like hypotension, altered mental status, maybe multiple episodes
of vomiting and fever with a history of recent surgery or significant trauma.
And hopefully they'll get that priority and be placed in a bed or a stretcher
or somewhere for a rapid assessment by a physician so that they can
quickly have those things addressed.
Interestingly, I thought this was another fun little tidbit, when a
hospital implements a clinical decision support tool in the EMR, there was one
study that showed that the patients in adrenal insufficiency were three times
more likely to receive hydrocortisone and two and a half times more likely to
get the right dose of hydrocortisone.
So pushing that information to the physicians and to the clinicians who
are doing the work at the bedside is helpful and is a good reminder
of the appropriate dose and to actually give it sooner than later.
And that's one of the benefits of electronic health records.
It's just such a great hope for me, for EMR.
Like reading this article, I could see how if you basically could just
pull that this patient already has Addison's or adrenal hyperplasia, and
you basically could then say, hey.
This patient is hypotensive, they have this condition.
Would you like to give steroids?
The recommended steroid is hydrocortisone.
Here's the recommended dosing.
Would you like to just click this button?
God, God bless it.
That would be such a wonderful, smart tool that I would be so on
board with because of all the times that I'm literally trying to like do
lifesaving things and it's like, have you looked at the patient's COWS?
Have you done any tobacco cessation counseling?
And I'm like, no, they're not really still like alive, so I'm gonna try to keep them
alive and we'll get to the other stuff.
Okay EMR?
and EMR's like, okay, I'll just remind you in five minutes.
I mean, I know the researchers from Epic listen to our podcast every month.
So once again, you know, researchers, you're there, you're listening.
Here's our EMR plug for the month.
If you could please include a big red button that would tell
us to give hydrocortisone, we would be greatly appreciative.
And just while we're at it, just if you could please, once I test the patient for
pregnancy, stop asking me if I'm sure.
I'm sure.
If I have a result and it's negative, I'm sure.
You don't need to, you don't need to warn me anymore.
I'm good.
Not related to this, but still important for our researchers who are listening.
Very important.
All right.
The next step, of course, is going to be obtaining your history, and there are
some things that you're going to want to ask, especially regarding their history of
adrenal insufficiency, their medications, and anything regarding signs and symptoms.
And once again, there's a handy table.
Table three on page seven, common precipitating factors, signs, and
symptoms in patients with adrenal crisis.
So you want to ask about GI illnesses and infections and surgeries and recent
trauma, recent physical stressors, pain, psychological stressors because
those can precipitate adrenal crisis.
Inadequate medication dosing.
You want to ask about pregnancy, MI, pulmonary embolism, and
other idiopathic factors.
All of these are precipitating factors.
And then you wanna ask those signs and symptoms of an adrenal crisis,
nausea, vomiting, fatigue, weakness, anorexia, dizziness, hypotension, altered
mental status, hyperpigmentation of the skin and abdominal pain or fever.
All of those, again, very nonspecific, but taken in some total in the right
clinical scenario should start to ring some alarm bells in your brain.
Interestingly, adrenal crisis is most commonly precipitated by an infection.
And in children it's typically viral.
And in adults it's typically bacterial, which I found to
be an interesting distinction.
And in about 10% of cases, adrenal crises have no precipitating
factor that we can figure out.
It just occurs and it's kinda like idiopathic or, or we just
are unable to stumble upon the correct precipitating factor.
So don't get too frustrated if you can't figure out why it occurred.
Just pat yourself on the back for having actually made the diagnosis.
I also thought that helped me 'cause I'm not dying to slam kids with steroids and
antibiotics all the time, but adults in the age of sepsis, I don't really feel bad
about slamming anybody with antibiotics.
So I think now chasing a little bit of fluids with a little bit of
steroids to make sure I'm not missing something, feels a little bit more
like a reasonable treatment plan.
And again, if you're a listener, you could go back a couple, three, four
episodes back and listen to our podcast on septic shock with a different author.
And she did a great job of kind of delineating, at least in her
practice, at what point she gives stress dose steroids to all of
her patients who are on pressors.
And, you know, whether that be immediately on initiation or if they
don't immediately respond to the pressors, she's giving those stress
dose steroids because it's just so common and it's just so frequent that
a dose of hydrocortisone is lifesaving.
And of course don't forget to ask about exogenous steroid use, and I found it very
interesting that the authors included the evidence from the, I don't know how to say
this now, this is gonna be Broersen et al performed a meta-analysis of 74 articles.
This was like almost 4,000 patients, and found the rate of adrenal insufficiency to
be 4.2% for patients receiving intranasal corticosteroids on a regular basis.
So you know you're using the nasal steroids for seasonal allergy disorder
and you're on it all year round, you are at higher risk for adrenal insufficiency
and 6.8% for inhaled corticosteroids.
So all of your asthmatic patients on inhaled steroids who receive that
for daily control are now at higher risk for adrenal insufficiency.
And I gotta tell you, that is not something I ever considered
to be a risk factor for adrenal insufficiency or crisis.
I think that was what I was getting to earlier is the
combination of those things.
'cause I know there's a lot of people on nasal and inhaled and now they're
older and maybe they get an injection in their knee or something, in their back.
And that additional cascading levels of steroid use exogenously
can push them over the top.
And to your next point, chronic opiate use has been shown to disrupt the HPA axis.
So now those patients are starting to filter into my head that, you
know, if they've been on opiates for a long time, for their chronic back
pain or their chronic, you know, surgical pain that they've had, now
I'm a little bit more cautious that those patients aren't hypotensive just
'cause they're always on pain meds.
It's more that they're developing and, you know, some sort of crisis
and I need to intervene there.
So,
And again, this was a 2020 study, cross-sectional, a hundred patients.
So again, pretty small, but it found that patients who were on 20 morphine
milligram equivalents of opioids per day or more were at a higher risk.
If they're on less than that, then generally they weren't associated with
a higher risk of adrenal insufficiency.
But definitely if they're on the higher doses for chronic opioids, just
one more risk factor to think about.
And you mentioned intraarticular injections, that's even more
than the other steroid use.
So 52% of those are at higher risk for adrenal insufficiency.
So just so many things, steroid use, don't just think about the
pills or recent prescriptions.
You gotta ask about other methods of delivery and opioids.
And then additional risk factors for patients during the history would be
things like, do they have diabetes?
Are they altered, do they have a history of asthma or coronary
disease or cardiac disease?
All of those things raise their risks for adrenal crisis.
Five Norcos a day gets you to 20 milligrams of morphine equivalents.
So I think that it really doesn't take much to get over 20 morphine
equivalents just for those of us keeping score at home on the MME calculator.
There you go.
Easily available on MD calc.
Which brings me to our next question in trivia with TR, which of the
following is the most reliable predictor of a future adrenal crisis.
So these are historical items.
All right.
Which of the following is the most reliable predictor
of a future adrenal crisis?
A, age over 60 years.
B, chronic opioid use.
C, history of adrenal crises.
D, inhaled corticosteroid use, or E, a pituitary tumor.
I think it's if they had a prior adrenal crisis, that's
gonna lead them to another one.
There you go.
So that's all it's, I wanted to go with age.
I felt like it was a trap.
I was so excited about the first answer.
I was like, oh, it's age.
But like, if they've had an adrenal crisis, which is why you gotta ask them,
boy, have you ever had an adrenal crisis?
And they may not know, but they'd be like, oh, they, they kept me in the hospital
and gave me steroids for a few days.
Bang.
Sounds like an adrenal crisis to me.
Don't overthink it.
Here's the direct quote from the authors.
The most reliable risk factor for adrenal crisis is a history
of a previous adrenal crisis.
So the most important question you're gonna ask in the
history portion of your exam.
Alright, next.
Physical examination.
So this is gonna be brief, but there are some things you wanna keep in mind.
So, abdominal pain is a very frequent presenting symptom in adrenal crisis.
And because abdominal pain is a frequent presenting symptom for multiple
diseases, you just gotta be careful.
So you need to address it, you need to address it in your ED evaluation and
make sure that you're not missing a alternate or a precipitating diagnosis as
the cause for the adrenal insufficiency.
So yes, they may have adrenal crises and abdominal pain, but they may have
also had appendicitis as their inciting incident that put them in adrenal crisis.
So don't forget about that.
And then there are gonna be some of those kind of House MD clues that
you're gonna pick up on physical exam.
Things like skin hyperpigmentation in the sun exposed areas, on the
flexor surfaces, on mucus membranes.
They might be underweight and chronically ill with thinning hair, especially in
the axillary areas in females, or if they have a secondary or tertiary adrenal
insufficiency, they're not gonna have that hyperpigmentation and they may actually
be overweight and have the same thinning axillary hair or if they've been on
long-term chronic steroid use, they may be cushingoid not from adrenal insufficiency,
but from the medication itself.
So if they're cushingoid on exam, they're gonna have the truncal obesity,
the big buffalo hump on the upper back and some supraclavicular fat
pads, moon facies, and worsening acne.
All of those are common things that you might pick up on exam for someone
who's had chronic steroid use.
And really, you may be asking, well, why is that even important?
Can I just ask them?
And honestly, if they're not altered, yes, you can say, are you on steroids?
But if they're confused or they have altered mental status or if they're
obtunded, you're not gonna get that information from the patient.
And these may be your only physical examination clues
that you're gonna pick up.
And once again, brings me to another trivia question.
Which physical examination finding is most specific for
primary adrenal insufficiency.
So the most specific exam finding for primary adrenal insufficiency.
This is at the adrenal gland.
Axillary hair thinning, B buffalo hump.
C, moon facies.
D, skin hyperpigmentation, or E, truncal obesity.
Run through those one more time.
A, axillary hair thinning, B, buffalo hump, C, Moon facies, D, skin
hyperpigmentation, or E, truncal obesity.
I don't know.
The answer is skin hyperpigmentation.
And I'll tell you, it's kind of a trick question, because three of these
things are actually not associated with primary adrenal insufficiency, but are
side effects of chronic steroid use.
It's that cushingoid appearance.
So that's the buffalo hump, the moon facies, and truncal obesity.
Those things you can kind of put aside, 'cause that's from chronic steroid
use which leaves us with axillary hair thinning, which can definitely
occur and skin hyperpigmentation.
But it turns out that the most specific one is the skin hyperpigmentation.
It's so rare though, 'cause primary is so rare.
Like you're gonna see that so, so rarely.
It'll be one of those interesting things if you notice it.
It's such a cool thing to catch.
'cause as you said, all the rest of it you're gonna see but,
Alright, let's drop in to some diagnostic studies.
So we like to order a bunch of things in the emergency department and that is
definitely a trend that's gonna continue in adrenal insufficiency and crisis.
Unfortunately the authors were quick to point out, there's no currently
accepted universal definition for adrenal crisis, which is kind of
frustrating really because it's an important diagnosis to not miss.
It is one that has some vague symptomology and can be easily missed
because of its overlap with other diseases, and it does not have a
universally accepted definition.
So, the authors suggest that a generally accepted definition would be
someone who has absolute hypotension.
So systolic blood pressure less than a hundred, or relative hypotension,
more than 20 millimeters of mercury lower than their usual blood pressure,
that resolves within one to two hours after administration of hydrocortisone.
So really they have the hypotension.
You suspect that, you give 'em the hydrocortisone, and then within
an hour or two they've improved.
That's generally accepted as, yes, they had an adrenal crisis, but interestingly,
it's retrospective, so you can't make that diagnosis prospectively and
go, oh, they have an adrenal crisis, I'm gonna give 'em hydrocortisone.
It's like, I think they might have it.
I'm gonna give them the steroids and see what happens, which is exactly
what we want you to do in the ED.
Act on that suspicion.
Laboratory studies, you're gonna get your chemistries, you're gonna get your
metabolic profiles, and it's important to know that it can be associated
with hypoglycemia, hyponatremia, hyperkalemia, hypercalcemia, and anemia.
So low blood glucose, low sodium, high potassium, high calcium, and anemia.
And among your other tests, so remember, it's important to figure out what
their precipitating diagnosis was.
You're gonna be sending those sepsis labs, getting those cultures, starting
antibiotics, doing all that other stuff.
But you should consider something like a serum cortisol, an ACTH level,
renin, and aldosterone levels, and a TSH with the reflexive T3, T4.
All of those are markers for the hypothalamic, pituitary,
and adrenal functions.
And the endocrinologist or your very adept critical care physician or hospitalist
is gonna come in after you and put all that together and say, ah, the
problem is here at the pituitary gland.
And that may guide subsequent imaging, which we'll get to in a minute.
So, important to send all of those labs.
The gold standard for diagnosing primary adrenal insufficiency is
the cosyntropin stimulation test.
Which is not something that you're gonna do in the ED because
you don't have time for that.
But there are other things like morning cortisol levels, random
cortisol levels, that can be followed.
And again, those can be drawn later.
They might be drawn in the emergency department.
Your hospitalist colleagues may add those on.
Just know that those are all part of the package for trying to
determine where the problem lies.
Is it primary, secondary, or tertiary?
The cosyntropin tests are affected by exogenous steroids.
So doing that, like in the emergency department, when the patient's
unstable, makes the results unreliable.
So if your admitting team or your endocrinologist team is trying to push
you to do this, you're welcome to push back and say, Hey, I think that's a
good idea to do that when the patient's stable, but it's not the right time to
do that here in the emergency department.
Save their life first.
Worry about the blood test later.
It's kind of very similar to like meningitis and
sepsis and all those things.
Did you get the culture?
Did, did you get some CSF yet?
I'm like, well, I was kind of concerned with saving their
life, but I'll get there.
All right, let's do another question.
This question is ideally answered while you are looking at figure one on page
five, that wonderful illustration, all right, referring to that figure in
tertiary adrenal insufficiency, so this is adrenal insufficiency at the hypothalamus,
most often caused by steroids.
What is the expected pattern for your cortisol level, your
ACTH, and your CRH levels?
Can I just tell you what it is?
Because if you're that high, so if the dysfunction, this is tertiary
adrenal insufficiency, then you're gonna have low levels across the board.
So you'll have low CRH, low ACTH, and low cortisol levels.
Bingo.
Exactly right.
So your corticotropin releasing hormone, that hormone released by
the hypothalamus, is gonna be low 'cause that's where the problem lies.
But also your adrenocorticotropic hormone, that's the ACTH released by the pituitary,
is also going to be low because it's not getting stimulated by the hypothalamus.
And your cortisol level is going to be low.
That's released by the adrenal gland, but also not being
stimulated by the pituitary.
So the downstream effects, all low, because the problem
lies at the hypothalamus.
Well done, sir.
One quick caveat, one quick thing I would wanna add to that, which I noticed as I
was remembering this, is your aldosterone levels are low in primary, but they're
usually normal in secondary and tertiary.
So that's something to not be led astray by, that your aldosterone
levels can be normal, but your cortisol levels can be low, and that
still means you've got dysfunction higher up in secondary and tertiary.
And if you remember from the physiology days, the aldosterone has
to do with your renin aldosterone system and your kidneys and salt.
And that is a communication between your adrenal glands and your kidneys.
And much less to do with anything pituitary or hypothalamic.
So if the problem is not at the adrenal glands, that portion of your adrenal
cortex will be functioning correctly.
Which is why the aldosterone level will be normal if it's secondary or tertiary,
so yes, excellent thing to point out.
All right, let's talk about imaging.
So again, you're gonna get imaging that's going to guide you to exclude all
of the other precipitating diagnoses.
So whatever you need to make sure they don't have some life-threatening
infection or an abdominal infection or whatever it is you need there.
But also if you are able to identify the location of the problem.
So if you're able to say, oh, this is a secondary or tertiary abnormality, that
may lead to additional brain imaging.
We're talking things like MRI imaging of the pituitary or MRI imaging
of the hypothalamus in order to discern what the problem may be.
Things like pituitary hemorrhage or an infiltrative process like
sarcoidosis or damage to the area from brain radiation that they've had.
All of those things can cause necrosis in the brain and cause those secondary
or tertiary effects, and that can be ordered later by your inpatient team
after you've done a great job saving their life and resuscitating them.
Or if they've had a trauma or a surgery recently, that may be something you want
to pursue a little bit quicker and sooner.
And also to consider involving your neurosurgery colleagues,
especially if it's one of their patients, to make sure you get the
kind of pictures that they want.
Alright, let's jump into treatment.
So when we talk about treatment, we're gonna talk about hydrocortisone, right?
As I mentioned before, a million times, we're talking about hydrocortisone.
If you suspect it, you're giving it, and the standard adult dose is
a hundred milligrams intravenously.
If you don't have IV access, it can be given IM, so don't wait.
If they're critically unstable and you're already suspecting this, just
give 'em the hydrocortisone IM while you're waiting to get IV access and
give it to 'em as soon as possible.
Now, that's just the initial dose.
It is later going to be followed by 200 milligrams a day as either a continuous
infusion or as bolus dosing every six hours at 50 milligrams a piece.
So just know that if they're hovering in your emergency
department for a long period of time, they've become more stable.
Maybe they've been downgraded from an ICU bed and they're waiting for a floor bed,
and now they're becoming more unstable.
It's probably because they're due for their next dose and you gotta make sure
that that's a priority to be administered.
The pediatric dosing is 50 milligrams per meter squared of body surface area.
And that, again, is given IV or IM, and then followed by either
a continuous infusion or the same every six hours divided dosing.
So just know, again, if they're hovering in your department for a long period
of time, they need that repeat dosing.
And the best medication is hydrocortisone.
Stress dose steroids can also be given with other steroids.
So for adults you can give methylprednisolone 40 milligrams
IV every 24 hours, or it can be Prednisolone 25 milligrams orally,
followed by two additional 25 milligram doses in the first 24 hours.
There's multiple different ways to break this up with Prednisone
and Prednisolone as a possibility.
But in the emergency department by far, if they're not taking anything orally,
it's gonna be IV or IM hydrocortisone.
And then you're gonna need to fix their fluid status.
So these people are getting fluid boluses.
You're gonna need to fix hypoglycemia.
You may need to add some D5 in there.
And then further treatment becomes tailored, depending on their response,
depending on what you find from your adrenal crisis laboratory testing,
and depending on what their subsequent diagnosis to put them in the adrenal
crisis is eventually elucidated to be.
So you gotta treat their sepsis or their appendicitis, or
whatever it is that occurred to set them in the adrenal crisis.
There are patients who have recommended sick day dosing.
So they're already on hydrocortisone at home and when they get sick,
their endocrinologist has educated them or the parents that this is
your sick day dosing, meaning we're going to double your hydrocortisone.
Typically that's doubled for fever over 38 degrees centigrade or tripled for
a fever over 39 degrees centigrade.
And that's continued for the entire duration of the illness.
So if it's a child and they've got a URI and they're spiking fevers, they're just
gonna stay on that stress dose steroid.
You might notice, well, the parents doubled it, but the
patient's not improving.
And it may be just that the fever's gotten so high, they now
qualify for the triple dosing.
So keep that in mind that it may just be subtherapeutic, even at the doubled
level and that that can be given at home.
And when they fail that and they come to the emergency department, we're
switching back to hydrocortisone.
There are some patients who give hydrocortisone IM at home.
Now this is not available yet in an auto-injector, so they're drawing
this up and injecting it themselves.
They may have prefilled syringes at home.
But again, another important piece of information for our EMS colleagues
to extract from the family, and it's important to know when their last dose
was because you're gonna need to repeat it in the ED or in the hospital to make
sure that they're not missing those doses.
I've embraced metric for measurements.
I'm here for that, but I refuse to embrace Celsius temperatures.
So for those like me, 38 celsius is 100.4, so they're getting double their
dose if they're over a hundred, and they're getting triple their dose
if they've hit 39, which is 102.2.
Over 102, they're getting triple dose, over a hundred,
they're getting double dose.
For those of us that wanna live and breathe by my friend Fahrenheit.
. And then there's maintenance therapy.
So typically patients who are on maintenance therapy are
on two different medications.
They're taking hydrocortisone and they're taking fludrocortisone.
So they're maximizing both the glucocorticoid and the mineralocorticoid
replacement therapy in order to make sure that they're perfectly balanced.
And the dosing is there for you in the article, but most cases,
that's not really gonna apply to us in the emergency department.
We're giving the stress dose, adrenal crisis dosing for the sickest of the
sick in order to turn 'em around quickly.
Which brings me to more trivia questions.
Here we go.
Which of the following is the recommended initial IV dose of hydrocortisone for
pediatric patients in adrenal crisis?
So IV dose peds patient in adrenal crisis.
Can I just give it to you?
'cause I have it memorized in my brain.
I know for sure that it is 50 milligrams per meter squared.
So I believe that is not a weight-based dose, but a surface area based dose.
And I would tell you that my one walk away from this is, I honestly
need to go look up how do I measure the surface area of a child?
'cause I don't know that off the top of my head.
MD Calc is your friend,
Hey, there you go.
MD calc plug.
Always your friend.
There's always something there to help you calculate.
And there is a calculator for body surface area in children.
Which of the following actions should be taken first when adrenal
crisis is suspected in the ED?
A, await cortisol lab results.
B, consult endocrinology.
C, order abdominal imaging.
D, perform the cosyntropin stimulation test, or E, administer
parental hydrocortisone.
Sorry, I missed the question.
I was looking up the body surface area calculator 'cause
I was so excited about it.
You're gonna have to hit me one more time.
Which of the following actions should be taken first when adrenal
crisis is suspected in the ED?
What's the first thing you gotta do?
Give IV hydrocortisone or IM hydrocortisone.
Give the hydrocortisone, do not delay therapy.
Alright, one more question.
100 or 40 of solumedrol if you don't have hydrocortisone.
'Cause sometimes I think I talk to pharmacy and they're like,
oh yeah, we'll get that for you, and then it's gonna be a while.
So that'd be something where I'd give pharmacy like, you know, 20 minutes and
then I'm giving them IV, whatever I got.
So if you're the director or if you're involved in administration or if
you're the pharmacy representative for your physician team in the ED,
this is one of those medications you really want in at least one
Pyxis machine in your department.
Because you don't have the luxury of waiting an hour for this to come
in the tube system from pharmacy.
You need this medication right away.
And honestly, if they're in crisis, an oral medication, you know, I mean
it's better than nothing, but it's not likely to get absorbed systemically
in the same manner as it would if they were just having a routine dose.
'cause if they're having GI issues, if they're having nausea or vomiting
or diarrhea, all of that reduces your absorption and is gonna reduce
your serum levels and it's not ideal and you're gonna be looking
for something IM, so you want that hydrocortisone available to you for sure.
Okay.
And this speaks to the last thing that you just mentioned.
For a patient with adrenal insufficiency who has a fever of 39.5
degrees Celsius, how should their hydrocortisone dose be adjusted?
Over 102 so you triple it.
There you go.
Triple the dose if they're over 39.
. Alright, let's just talk about a couple of special populations.
First is pregnancy.
So yes, people with adrenal insufficiency can become pregnant and when they do, they
still have to continue their medications.
So hydrocortisone is the glucocorticoid of choice and it
is inactivated by the placenta.
So it's not crossing that placental barrier, but it's critically important.
And depending on their stage of pregnancy, they may need increasing
doses as they progress through pregnancy.
And then they may need stress doses in certain situations.
So during labor a huge stressor and they're gonna need to be on
the full stress dosing there.
If they end up getting a C-section or having surgery,
again, full stress dosing there.
But also early in pregnancy, there's significant overlap between hyperemesis
gravidarum and adrenal crisis because of that persistent nausea and vomiting.
And it can be hard to tease it out.
So is this hyperemesis or is this their adrenal crisis cropping up again?
And you may need to do some stress dosing around those times as well.
So just understand that there's some overlap there and it can
be a little bit confusing.
Not a bad idea to consult their OBGYN as well.
'cause they probably have struggled with this before.
I think that's gonna be our lasting impression as we finish this thing up
is, you know, do the thing, but then get the consultant and get them admitted.
And then your patients with septic shock.
So there's a little paragraph here, but again, if you want to hear more
about this, go back a few episodes to our septic shock episode.
And we talked about this extensively.
There is a role for hydrocortisone in patients in septic
shock who were on pressors.
There is actually a mortality benefit.
And that leads me to our last two trivia questions.
Alright.
This one's a case, a 38-year-old woman presenting with fatigue,
weight loss, and craving salty foods, appears unusually tanned and has labs
revealing low sodium, mildly elevated potassium and a glucose in the sixties.
What diagnosis should be strongly considered?
We've got addison's disease, diabetes insipidus, Hashimoto's
thyroiditis, or pheochromocytoma.
She sounds like an Addisonian crisis to me, and I'm gonna
give her some hydrocortisone.
She is adrenally insufficient.
She's not yet hypotensive, at least not given in the case.
But absolutely someone who sounds like she has Addison's disease and you gotta send
off all those labs and give her a little dose of steroids and see how she responds.
And then the final question, which of the following is a documented pitfall in
ED management of adrenal insufficiency?
So which one of these mistakes do we know we make.
Administering fludrocortisone before labs, delaying corticosteroids to
confirm diagnosis, overtreating with glucose before cortisol, initiating
vasopressors too early, or administering hydrocortisone without consent.
Honestly, I think in this case, almost always, it's you can talk yourself into
something else and you delay giving the hydrocortisone, and I think this
is a good time to say, you know, could be this, could be this, could be this.
So just to cover myself for some sort of adrenal crisis, I'm
gonna give the steroids and then I'll let it play out upstairs.
And that, ladies and gentlemen, is it for us.
So the takeaway message being have a high suspicion and a very low
threshold for giving the hydrocortisone.
And don't wait for your labs.
Send them off.
But give the hydrocortisone.
Don't forget that the accepted definition involves the treatment.
So suspicion isn't enough.
And if you think they have the diagnosis, give 'em the hydrocortisone
and see if they respond.
And that's it for our Emergency Medicine Practice October 2025 article.
Thank you to the Simcoes for authoring this outstanding
review of adrenal insufficiency.
Keep it in your office in your little physician lounge.
Keep the article handy.
Keep the references on your phone and just keep that diagnosis in the
forefront of your brain next time you see somebody who's unstable and altered.
Good luck out there.
You're gonna get one of these a season.
It's a good catch if you catch it.
All right, ladies and gentlemen, until next time, be safe.
And that's a wrap for this month's episode.
I hope you found it educational and informative.
Don't forget to go to ebmedicine.net to read the article and claim your CME.
And of course, check out all three of the journals and the multitude of
resources available to you, both for emergency medicine, pediatric emergency
medicine, and evidence based urgent care.
Until next time, everyone be safe.