Adrenal Insufficiency

In this episode, Sam Ashoo, MD and T.R. Eckler, MD discuss the October 2025 Emergency Medicine Practice article, Emergency Department Evaluation and Management of Patients With Adrenal Insufficiency

Introduction

• Welcome and host introductions
• Brief overview of the episode’s topic
• Resources and CME reminder

Article Overview

• Source: Emergency Medicine Practice, October 2025
• Authors: The Simcoes
• Importance of evidence-based review

Clinical Context & Epidemiology

• Frequency and rarity of adrenal insufficiency
• Diagnostic challenges and statistics
• Importance of recognizing adrenal crisis

Pathophysiology

• Primary, secondary, and tertiary adrenal insufficiency
• Causes and mechanisms
• Key anatomical and physiological concepts

Differential Diagnosis

• Overlap with other diseases (infections, autoimmune, endocrine, psychiatric, cardiac, GI, etc.)
• Importance of considering adrenal crisis in complex cases

Prehospital Care

• EMS recognition and limitations
• Importance of medication history and emergency kits
• Legal and logistical barriers to prehospital hydrocortisone

Emergency Department Evaluation

• Recognizing symptoms and prioritizing care
• Role of EMR and clinical decision support
• Key history and risk factors (medications, steroid use, opioid use, comorbidities)

Physical Examination

• Specific and nonspecific findings
• Cushingoid features vs. primary adrenal insufficiency signs

Diagnostic Workup

• Laboratory studies (cortisol, ACTH, renin, aldosterone, TSH, etc.)
• Imaging considerations
• Gold standard tests and their limitations in the ED

Treatment

• Immediate administration of hydrocortisone
• Dosing for adults and pediatrics
• Supportive care (fluids, glucose, treating underlying cause)
• Sick day dosing and home management

Special Populations

• Pregnancy considerations
• Septic shock and adrenal crisis

Common Pitfalls & Takeaways

• Delaying steroids for labs/diagnosis
• Importance of high suspicion and early treatment
• Key trivia and learning points

ClosingSummary and final thoughts

• Reminders for further reading and CME
• Farewell and next episode teaser

Emergency Medicine Residents, get your free subscription by writing [e-mail]

Episode Transcript

(00:00):
I'm like, no, they're not really stilllike 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'lljust 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.

(00:21):
I sincerely hope that you find it tobe helpful and informative for your
clinical practice, and I want to remindyou that you can go to ebmedicine.net
where you will find our three journals,Emergency Medicine Practice, Pediatric
Emergency Medicine Practice, and EvidenceBased Urgent Care, and a multitude of
other resources, like the EKG course,the laceration course, interactive

(00:42):
clinical pathways, just tons ofinformation to support your practice
and help you in your patient care.
And now, let's jump intothis month's episode.
All right, ladies and gentlemen, welcomeback to another episode of EMPlify.
I am one of your hosts, SamAshoo, and on the other end of
the microphone joining me today.
TR Eckler, back feelingsalty, but a little sweet.

(01:04):
That's, that's so apropos becausetoday we are reviewing the Emergency
Medicine Practice article fromOctober 2025, Emergency Department
Evaluation and Management ofPatients With Adrenal Insufficiency.
You ever seen one ofthese patients in the ED?
A few, not many.
Now I will tell you this is what I tookaway from this article, is that the ones

(01:25):
that know they have it are very smartand will tell you exactly what they need
and are generally very well educated.
And then now I think there'smore people that are on so many
different kinds of steroids.
You're seeing those humans creep intothe emergency department and they
creep in with sepsis or they creep inwith, you know, a nasty viral infection

(01:46):
and they're a little hypotensive.
And I think now I'm more worried aboutthis overlap between infection and chronic
steroid use driving more of these patientsmy way and I need to be a little quicker
on the gun with steroids for these people.
If I'm gonna sling antibioticsat everybody for sepsis, I think
I'm a little closer to slinging alittle bit of a hydrocortisone or
Solu-Medrol at everybody as well.

(02:08):
'Cause I think I'm gonna getmore hits than misses there.
Yeah, I am fortunate or unfortunateenough, I'm not really sure which way this
goes, but to have seen someone go fromlike death's door to awake and totally
normal after a dose of hydrocortisone.
Like going from, hey critical careteam, I need you to come down now.
We're starting pressors.

(02:29):
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'relike, hey, person looks like a rose.
What are you, what are you panicked about?
And I'm like, well, 30 minutesago it didn't look like this.
If data serves, in a few hours, they'lldo this again, so you should probably
be the one to catch them before that.
They're gonna need some repeat dosing.

(02:50):
But this is a, onceagain, fantastic article.
This one was authored by the Simcoes,a husband and wife team who did
an outstanding job reviewing allthings adrenal insufficiency and
adrenal crisis with, as always, anevidence-based literature search.
And I think it was very good actually,of them to point out that there isn't

(03:10):
all that much great literature whenit comes to adrenal insufficiency and
adrenal crises and that randomizedcontrol trials are mostly unethical
when we talk about, you know, do wewithhold certain lifesaving medications?
But there are some advancementscoming down the pipeline with
medications, I hope, and we'll getto all of that here pretty soon.

(03:31):
I did, as always, look at theintroductory epidemiology information,
and I'm always taken back by likethe frequency of these things.
Adrenal insufficiency is still considereda rare condition, like 200,000 people
in the United States with an estimated20,000 adrenal crises events per year.
That's not really a smallnumber in the country.

(03:52):
And there was a study in 2010, said 67%of patients with adrenal insufficiency
had consulted at least three physiciansbefore getting the diagnosis, and
20% had suffered symptoms for fiveyears before getting the diagnosis.
So this is definitely somethingthat is a chronic illness and is

(04:13):
really a diagnostic challenge.
And hopefully after today'sdiscussion, everybody listening
will understand why as well
I try to put numbers like these in contextjust a little bit 'cause I actually
thought that number was a little bit low.
But this is one of those kind of fun oneswhere I like to stop for a second and
be like, how many emergency departmentsare there in the United States?
So like, estimates arebetween five and 6,000.

(04:36):
So this means that somewhere around likefour times a year, you're gonna see a
patient like this roll into your ER.
Now that's gonna vary by size and allkinds 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 andevery gastroenteritis that's hypotensive
has got this adrenal crisis, but every nowand again, one of these is gonna try to

(04:59):
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 afterhearing this and reading this article and
studying and taking the CME test to pickthis up, I think you do your colleagues
and especially the patient, a huge favor.

(05:20):
The foundation for adrenalinsufficiency and adrenal crises really
starts with the physiology of it.
And this kinda hearkens backto medical school and what we
learned as primary, secondary, andtertiary adrenal insufficiency.
And you know, I'm not sure I was thatawake when I heard this the first

(05:41):
time around, but there is a fantasticillustration, figure one, which shows
you the brain, the hypothalamus, thepituitary gland and the adrenal glands
and describes in very simple detailwhy this is a problem and how it works.
And I kind of wish I'd had thisfigure when I was in medical school.
Honestly.
There are three locations involvedin adrenal insufficiency, right?

(06:05):
There's the adrenal glands, whichsit right above the kidneys.
There's the pituitary gland, which sitsat the base of the brain, and then there's
the hypothalamus, and any one of thosethree can be problematic, and depending on
where the problem is, you get a diagnosisof primary, if it's at the adrenal glands,
secondary, if it's at the pituitary andtertiary adrenal insufficiency if it's

(06:27):
at the hypothalamus further up in thebrain and the causes for those can vary.
So primary is actually the least commonof the three and is typically autoimmune.
It can be congenital, so youcan be born with that condition.
You can have congenital adrenalhyperplasia in children, or you can
develop Addison's disease as an adult.

(06:49):
But it can also be associatedwith infections like tuberculosis.
So especially in the developing worldwhere tuberculosis is still rampant
this is a more common occurrence.
Secondary adrenal insufficiencyis sort of in the middle and is
caused by a disruption of thishypothalamic pituitary adrenal axis.

(07:13):
So it's disrupting the signalsbetween all three of these areas by
affecting the pituitary gland, andit's most commonly due to pituitary
tumors or trauma or radiation.
Which kind of makes sense.
And then the tertiary, the onethat's highest up in the brain
adrenal insufficiency is causedby typically glucocorticoids from

(07:34):
all the steroids we give people.
So if you haven't heard that wordof caution, go back one episode and
listen to my conversation with my guestjust a couple of weeks ago about the
problems that occur from even short termsteroid use, and you'll understand why
we prescribe so many of these things,why they're causing such problems.
So that's tertiary adrenal insufficiencyand the foundational physiology for all of

(07:59):
this comes together when you think aboutthe adrenal gland as having three layers.
Zone one or layer one has to do withthe mineralocorticoid, aldosterone.
Zone two has to do with theglucocorticoid, cortisol.
And zone three is responsible for allof the androgens and in the crises and

(08:20):
the insufficiency we're going to betalking about today, we're discussing
the problems of insufficient aldosteroneand cortisol, or zone one and zone
two, and so once you understand thatphysiology, you can refer back to
things like this table and this figure.
And even later on when we talk aboutlabs and we talk about all the different

(08:40):
labs you need to order, you can discernwhich 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 inpatientrealm, all that testing we've ordered
comes back and somebody much smarterthan me is putting it all together

(09:04):
and making that formal diagnosisand telling you where the issue is.
Yeah, I, I think as you said, thatfigure is such a great summary of this,
and I think it really helps distill itto like where exactly the problem is.
I liked how I remembered this ona whiteboard in medical school,
and I remember the idea beingthat primary is the lowest.
It's at the level of the kidneys.

(09:24):
And then as you move up higher throughthe body up towards the brain, that's
secondary and tertiary and thatfollows with like where the problem is.
So if your cortisol levelsonly are low, that's primary.
When you start seeing lowACTH levels, that's secondary.
And then when all your levels arelow, your corticotropin-releasing
hormone, your ACTH, and your cortisol,that's coming from your hypothalamus.

(09:45):
So I like how the levels pointto where the problem is as you
go kind of more vertically.
It's a great figure and something youreally need to review every now and
then because it does get confusing ifyou're not looking at this every day,
you may remember that you have to sendthese labs, but you may not recall
exactly what it is that it all means.
And the mainstay of treatment, andwe will harp on this thousands of

(10:08):
times during this podcast today,but the mainstay of treatment for
adrenal crisis is administeringcorticosteroids that have both the
glucocorticoid and the mineralocorticoideffects, which is hydrocortisone.
So, you're gonna hear this amillion times, but the treatment,
the emergent treatment for adrenalcrisis is dosing hydrocortisone
without waiting for anything else,especially if you're suspicion's high.

(10:31):
And because it's been a while, we'regonna 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 commoncause of tertiary adrenal insufficiency.

(10:57):
Now, before we jump into the answers,tertiary is up at the hypothalamus.
Which of these is the most commoncause of adrenal insufficiency
up at the hypothalamus?
A, autoimmune B, chroniccorticosteroid use.
C, pituitary apoplexy.
D, tuberculosis, or E,Waterhouse-Friderichsen syndrome.

(11:21):
So despite my love for tuberculosisand the recently released book,
Everything is Tuberculosis, which Istrongly recommend everyone to read,
and my love for Waterhouse-Friderichsensyndrome because anytime you can tie
adrenal hemorrhages to meningitis andmake that diagnosis, it's awesome.
But I know that this is chroniccorticosteroid use because it's just so

(11:44):
rampant and something now that I'm muchmore aware of with my steroid prescribing.
There you go.
Tertiary adrenal insufficiency isthe most common cause of adrenal
insufficiency and it's caused mostoften by exogenous glucocorticoids.
Well done, sir. Well done.
All right.
Let's step out of the pathophysiologysection for just a moment and dive

(12:05):
into the differential diagnosis.
Now, this is exceptionally challenging,I think, because adrenal crises are
precipitated by diseases, infectionsprimarily, and the presentation
of adrenal crisis has significantoverlap in symptoms with many of

(12:27):
the diseases that cause the crisis.
So it's quite easy for us in theemergency department to get distracted
or maybe to stop once we've diagnosedthe precipitating disease and not take
the extra step of figuring out, oh,they're also adrenally insufficient,
and now in an adrenal crisis.

(12:48):
And that overlap and that lack ofmoving to that extra step is where
the increased mortality comes.
So there is once again, a fantastictable on page six if you have access
to the article, which lists thedifferential diagnosis for adrenal
insufficiency and not surprisingly, itincludes a bunch of things, infections

(13:10):
being at the top of the list, likechronic or long-term infections.
Things like HIV, tuberculosis, Lymedisease, long COVID, and hepatitis.
But there are other things as well,autoimmune diseases, diabetes,
malignancy, endocrinopathies likehypothyroidism, hyperthyroidism and
hyperparathyroidism, psychiatric disease,depression, anxiety, eating disorders,

(13:35):
renal insufficiency, both chronic andacute, cardiac disease like congestive
heart failure and cardiomyopathies, andgastrointestinal disease like chronic
liver disease and celiac disease.
All of these are included in thedifferential diagnosis for adrenal
insufficiency, but can also beprecipitating adrenal crises.
And I thought the authors actuallydid a pretty good job of perusing the

(14:00):
literature for case reports and notingthat relatively rare conditions, things
like tricyclic antidepressant overdoses,and takotsubo cardiomyopathies and
shock from anorexia have been diagnosedin the setting of adrenal crises.
And those diagnoses were mistakenlysettled upon in cases where the patient

(14:23):
was actually suffering an adrenal crisis.
Just further demonstrating theoverlap between all of these
multiple disease processes and thechallenge in making that diagnosis.
So the take home message here beingas you're entertaining multiple
diagnoses, and especially as youentertain some of the rarer causes,
don't forget about adrenal insufficiencyand think about crisis presenting as

(14:48):
the cluster of symptoms that you'reseeing in front of you right now.
All right, let's moveon to pre-hospital care.
As always, our pre-hospital colleagues maybe listening and do an outstanding job.
And this is, again, one ofthose challenging areas.
How is it that someone in the pre-hospitalsetting is going to come up with this
diagnosis when we even can't do it inthe emergency department quite often?

(15:09):
And the answer is in ways thatyou probably already understand.
So looking for things like, are theywearing a medical alert bracelet
or do they have a necklace thatsays, Hey, I have this condition.
Do they have a pill box tobe dosed in emergencies?
Did they mention that they're onmedications like hydrocortisone and that
they've been taking their stress dose?

(15:29):
All of these are importantfactors that may come from the
patient or from family members.
If it's a child, thismay come from the parent.
They may say, hey, yeah, they'vebeen ill for three or four days and
we've been giving this stress dosesteroids, but now we're having problems.
And so all of these are little historicalpieces that our EMS colleagues can

(15:49):
extract from family members or people atthe scene or hopefully from the patient.
And if the patient has an emergency kitwith extra pills in it, that's helpful
to bring along so we can identify those.
There was one questionnaire cited inthe article of 150 patients with chronic
adrenal insufficiency and found that59 of them had adrenal emergencies.

(16:11):
So about a third of themexperienced an adrenal crisis.
85% of those were already on theirstress dose steroids, so they may be
able to tell you, hey, I've been sick.
And I've been on my steroidsand I've been at the higher dose
and I'm still having problems.
And so that's an importantpiece of history to elicit
from the patient at the scene.

(16:32):
And there is a foundation called theCARES Foundation which has drawn attention
to the fact that many emergency medicalservices crews don't carry hydrocortisone.
It's not something that'stypically carried on an ambulance.
And there's usually not a protocolfor administering it pre-hospital.
And, you know, if it's a two minute driveto the hospital, maybe not a big deal.
But especially if you're out in a ruralsetting and you're gonna be taking

(16:54):
this person on an ambulance ride foran hour, that's a critical time where
you may be starting an IV, doing IVfluids, noticing that their shock is
getting worse and they're not responding.
And so this becomes a really importantpiece of history to obtain and a really
important medication to have on the truck.
Or to make sure if you don't have iton the truck that you see if they've
got it and you consider whether ornot you wanna call med control and

(17:18):
give them their dose before they go.
If for some reason they can'tgive it or they were afraid
to or something like that.
There's always those things.
I think to your point, the biggestvalue 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 orthey haven't been able to take this, or

(17:38):
they just got an injection here in theirback or in their knee or somewhere else.
And now I've really, from thisarticle 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 combinationthat you weren't on before?
And then did you stop somethingthat precipitated this?
And I think that's always gonna besomething that EMS is gonna tip that to

(17:59):
you, and really save your posterior if youjust listen hard enough to what's new and
what's actually getting taken versus not.
I'm a big proponent of EMS presentationsdirectly to the clinician, so you know, to
the nurse practitioner, PA, or physicianwho's at the bedside at the time that
they're there because oftentimes thisstuff can get lost in translation.

(18:20):
You know, they may givethis to the nursing report.
They may give it to a tech andsay, 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 ofinformation that should not be
lost in that communication gap.
Which brings me to our secondquestion in trivia with TR.
Prehospital management.
What the main limitation inprehospital care for adrenal

(18:46):
crisis in the United States?
So, which one of these is thebiggest stumbling block in the US?
A, no diagnostic criteria available.
B, EMS cannot legally administerhydrocortisone in some states.
C, parents are unableto recognize symptoms.
D, cortisol levels are too unstable, or E,hydrocortisone causes allergic reactions.

(19:13):
All right, one more time.
Yeah, I feel like C,D, and EI'm okay, but what was A and B?
A was no diagnostic criteria available.
B was EMS cannot legally administerhydrocortisone in some states.
C was the parents can'trecognize symptoms.
D was cortisol levels are toounstable, and E was hydrocortisone
causes allergic reactions.
Yeah, that's wild that there aresome states that don't allow EMS

(19:36):
crews to administer hydrocortisone,and this interests me, as an area
for advocacy, like, this would notbe so different than, you know, an
EpiPen, being able to administeran EpiPen if it's there, you know,
It is crazy, but the article actually doessay yes in the United States, some states
don't allow EMS personnel to administerhydrocortisone from the patient's own
emergency kit, so they can't administerit, but they may be able to open the

(20:00):
kit and put the pills in their handand say, hey, I'm just gonna help you.
Here are the pills.
It's very strange that such alaw would exist for a lifesaving
medication like hydrocortisone.
But indeed that is one of thestumbling blocks in the United States.
A little bizarre, but absolutely true.
All right, let's get to the ED evaluation.

(20:21):
When they arrive in the emergencydepartment, you want to recognize
the cluster of symptoms andprioritize these patients.
And in general, if they're in an adrenalcrisis, they're gonna be presenting
with something like hypotension, alteredmental status, maybe multiple episodes
of vomiting and fever with a history ofrecent surgery or significant trauma.

(20:42):
And hopefully they'll get that priorityand be placed in a bed or a stretcher
or somewhere for a rapid assessmentby a physician so that they can
quickly have those things addressed.
Interestingly, I thought this wasanother fun little tidbit, when a
hospital implements a clinical decisionsupport tool in the EMR, there was one
study that showed that the patients inadrenal insufficiency were three times

(21:06):
more likely to receive hydrocortisoneand two and a half times more likely to
get the right dose of hydrocortisone.
So pushing that information to thephysicians and to the clinicians who
are doing the work at the bedsideis helpful and is a good reminder
of the appropriate dose and toactually give it sooner than later.
And that's one of the benefitsof electronic health records.

(21:28):
It's just such a greathope for me, for EMR.
Like reading this article, I couldsee how if you basically could just
pull that this patient already hasAddison'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?

(21:50):
God, God bless it.
That would be such a wonderful,smart tool that I would be so on
board with because of all the timesthat I'm literally trying to like do
lifesaving things and it's like, haveyou looked at the patient's COWS?
Have you done any tobaccocessation counseling?
And I'm like, no, they're not really stilllike alive, so I'm gonna try to keep them

(22:12):
alive and we'll get to the other stuff.
Okay EMR?
and EMR's like, okay, I'll justremind you in five minutes.
I mean, I know the researchers fromEpic 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 abig red button that would tell
us to give hydrocortisone, wewould be greatly appreciative.

(22:33):
And just while we're at it, just if youcould please, once I test the patient for
pregnancy, stop asking me if I'm sure.
I'm sure.
If I have a result andit's negative, I'm sure.
You don't need to, you don'tneed to warn me anymore.
I'm good.
Not related to this, but still importantfor our researchers who are listening.
Very important.
All right.
The next step, of course, is going tobe obtaining your history, and there are

(22:54):
some things that you're going to want toask, 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, commonprecipitating factors, signs, and
symptoms in patients with adrenal crisis.

(23:14):
So you want to ask about GI illnessesand 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.

(23:35):
And then you wanna ask those signsand symptoms of an adrenal crisis,
nausea, vomiting, fatigue, weakness,anorexia, dizziness, hypotension, altered
mental status, hyperpigmentation ofthe skin and abdominal pain or fever.
All of those, again, very nonspecific,but taken in some total in the right

(23:56):
clinical scenario should start toring some alarm bells in your brain.
Interestingly, adrenal crisis is mostcommonly precipitated by an infection.
And in children it's typically viral.
And in adults it's typicallybacterial, which I found to
be an interesting distinction.
And in about 10% of cases, adrenalcrises have no precipitating

(24:19):
factor that we can figure out.
It just occurs and it's kindalike idiopathic or, or we just
are unable to stumble upon thecorrect precipitating factor.
So don't get too frustrated if youcan't figure out why it occurred.
Just pat yourself on the back forhaving actually made the diagnosis.
I also thought that helped me 'cause I'mnot dying to slam kids with steroids and
antibiotics all the time, but adults inthe age of sepsis, I don't really feel bad

(24:42):
about slamming anybody with antibiotics.
So I think now chasing a littlebit of fluids with a little bit of
steroids to make sure I'm not missingsomething, feels a little bit more
like a reasonable treatment plan.
And again, if you're a listener, youcould go back a couple, three, four
episodes back and listen to our podcaston septic shock with a different author.
And she did a great job of kindof delineating, at least in her

(25:03):
practice, at what point she givesstress dose steroids to all of
her patients who are on pressors.
And, you know, whether that beimmediately on initiation or if they
don't immediately respond to thepressors, she's giving those stress
dose steroids because it's just socommon and it's just so frequent that
a dose of hydrocortisone is lifesaving.
And of course don't forget to ask aboutexogenous steroid use, and I found it very

(25:25):
interesting that the authors included theevidence from the, I don't know how to say
this now, this is gonna be Broersen et alperformed a meta-analysis of 74 articles.
This was like almost 4,000 patients, andfound the rate of adrenal insufficiency to
be 4.2% for patients receiving intranasalcorticosteroids on a regular basis.

(25:49):
So you know you're using the nasalsteroids for seasonal allergy disorder
and you're on it all year round, you areat higher risk for adrenal insufficiency
and 6.8% for inhaled corticosteroids.
So all of your asthmatic patientson inhaled steroids who receive that
for daily control are now at higherrisk for adrenal insufficiency.
And I gotta tell you, that isnot something I ever considered

(26:11):
to be a risk factor for adrenalinsufficiency or crisis.
I think that was what I wasgetting to earlier is the
combination of those things.
'cause I know there's a lot of peopleon nasal and inhaled and now they're
older and maybe they get an injection intheir knee or something, in their back.
And that additional cascadinglevels of steroid use exogenously
can push them over the top.
And to your next point, chronic opiate usehas been shown to disrupt the HPA axis.

(26:36):
So now those patients are startingto filter into my head that, you
know, if they've been on opiates fora 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 thatthose patients aren't hypotensive just
'cause they're always on pain meds.
It's more that they're developingand, 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.

(27:00):
So again, pretty small, but it foundthat patients who were on 20 morphine
milligram equivalents of opioids perday or more were at a higher risk.
If they're on less than that, thengenerally they weren't associated with
a higher risk of adrenal insufficiency.
But definitely if they're on thehigher doses for chronic opioids, just
one more risk factor to think about.

(27:21):
And you mentioned intraarticularinjections, that's even more
than the other steroid use.
So 52% of those are at higherrisk for adrenal insufficiency.
So just so many things, steroiduse, don't just think about the
pills or recent prescriptions.
You gotta ask about othermethods of delivery and opioids.
And then additional risk factors forpatients during the history would be

(27:44):
things like, do they have diabetes?
Are they altered, do they havea history of asthma or coronary
disease or cardiac disease?
All of those things raisetheir risks for adrenal crisis.
Five Norcos a day gets you to 20milligrams of morphine equivalents.
So I think that it really doesn'ttake much to get over 20 morphine
equivalents just for those of us keepingscore at home on the MME calculator.

(28:08):
There you go.
Easily available on MD calc.
Which brings me to our next questionin trivia with TR, which of the
following is the most reliablepredictor of a future adrenal crisis.
So these are historical items.
All right.
Which of the following isthe most reliable predictor
of a future adrenal crisis?

(28:29):
A, age over 60 years.
B, chronic opioid use.
C, history of adrenal crises.
D, inhaled corticosteroiduse, or E, a pituitary tumor.
I think it's if they had aprior adrenal crisis, that's
gonna lead them to another one.
There you go.

(28:49):
So that's all it's, Iwanted 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 adrenalcrisis, 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 factorfor adrenal crisis is a history

(29:13):
of a previous adrenal crisis.
So the most important questionyou're gonna ask in the
history portion of your exam.
Alright, next.
Physical examination.
So this is gonna be brief, but thereare some things you wanna keep in mind.
So, abdominal pain is a very frequentpresenting symptom in adrenal crisis.
And because abdominal pain is afrequent presenting symptom for multiple

(29:35):
diseases, you just gotta be careful.
So you need to address it, you need toaddress it in your ED evaluation and
make sure that you're not missing aalternate or a precipitating diagnosis as
the cause for the adrenal insufficiency.
So yes, they may have adrenal crisesand abdominal pain, but they may have
also had appendicitis as their incitingincident that put them in adrenal crisis.

(30:00):
So don't forget about that.
And then there are gonna be some ofthose kind of House MD clues that
you're gonna pick up on physical exam.
Things like skin hyperpigmentationin the sun exposed areas, on the
flexor surfaces, on mucus membranes.
They might be underweight and chronicallyill with thinning hair, especially in
the axillary areas in females, or ifthey have a secondary or tertiary adrenal

(30:25):
insufficiency, they're not gonna have thathyperpigmentation and they may actually
be overweight and have the same thinningaxillary hair or if they've been on
long-term chronic steroid use, they may becushingoid not from adrenal insufficiency,
but from the medication itself.
So if they're cushingoid on exam,they're gonna have the truncal obesity,

(30:46):
the big buffalo hump on the upperback and some supraclavicular fat
pads, moon facies, and worsening acne.
All of those are common things thatyou 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 havealtered mental status or if they're

(31:09):
obtunded, you're not gonna getthat information from the patient.
And these may be your onlyphysical examination clues
that you're gonna pick up.
And once again, brings meto another trivia question.
Which physical examinationfinding is most specific for
primary adrenal insufficiency.

(31:30):
So the most specific exam findingfor 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.

(31:50):
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 atrick question, because three of these

(32:11):
things are actually not associated withprimary adrenal insufficiency, but are
side effects of chronic steroid use.
It's that cushingoid appearance.
So that's the buffalo hump, themoon facies, and truncal obesity.
Those things you can kind of put aside,'cause that's from chronic steroid
use which leaves us with axillaryhair thinning, which can definitely
occur and skin hyperpigmentation.

(32:31):
But it turns out that the most specificone 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 interestingthings if you notice it.
It's such a cool thing to catch.
'cause as you said, all therest of it you're gonna see but,
Alright, let's drop in tosome diagnostic studies.
So we like to order a bunch of thingsin the emergency department and that is

(32:53):
definitely a trend that's gonna continuein adrenal insufficiency and crisis.
Unfortunately the authors were quickto point out, there's no currently
accepted universal definition foradrenal crisis, which is kind of
frustrating really because it's animportant diagnosis to not miss.
It is one that has some vaguesymptomology and can be easily missed

(33:15):
because of its overlap with otherdiseases, and it does not have a
universally accepted definition.
So, the authors suggest that agenerally accepted definition would be
someone who has absolute hypotension.
So systolic blood pressure less thana hundred, or relative hypotension,

(33:36):
more than 20 millimeters of mercurylower than their usual blood pressure,
that resolves within one to two hoursafter administration of hydrocortisone.
So really they have the hypotension.
You suspect that, you give 'em thehydrocortisone, and then within
an hour or two they've improved.
That's generally accepted as, yes, theyhad an adrenal crisis, but interestingly,
it's retrospective, so you can'tmake that diagnosis prospectively and

(33:59):
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 andsee what happens, which is exactly
what we want you to do in the ED.
Act on that suspicion.
Laboratory studies, you're gonna getyour chemistries, you're gonna get your
metabolic profiles, and it's importantto know that it can be associated
with hypoglycemia, hyponatremia,hyperkalemia, hypercalcemia, and anemia.

(34:27):
So low blood glucose, low sodium, highpotassium, 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 sepsislabs, getting those cultures, starting
antibiotics, doing all that other stuff.
But you should consider somethinglike a serum cortisol, an ACTH level,

(34:50):
renin, and aldosterone levels, anda TSH with the reflexive T3, T4.
All of those are markers forthe hypothalamic, pituitary,
and adrenal functions.
And the endocrinologist or your very adeptcritical care physician or hospitalist
is gonna come in after you and putall that together and say, ah, the

(35:10):
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 diagnosingprimary adrenal insufficiency is
the cosyntropin stimulation test.
Which is not something thatyou're gonna do in the ED because

(35:31):
you don't have time for that.
But there are other things likemorning cortisol levels, random
cortisol levels, that can be followed.
And again, those can be drawn later.
They might be drawn inthe emergency department.
Your hospitalist colleaguesmay add those on.
Just know that those are allpart of the package for trying to
determine where the problem lies.
Is it primary, secondary, or tertiary?

(35:53):
The cosyntropin tests areaffected by exogenous steroids.
So doing that, like in the emergencydepartment, when the patient's
unstable, makes the results unreliable.
So if your admitting team or yourendocrinologist team is trying to push
you to do this, you're welcome to pushback and say, Hey, I think that's a
good idea to do that when the patient'sstable, but it's not the right time to
do that here in the emergency department.

(36:14):
Save their life first.
Worry about the blood test later.
It's kind of very similarto 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 ofconcerned with saving their
life, but I'll get there.
All right, let's do another question.
This question is ideally answered whileyou are looking at figure one on page

(36:34):
five, that wonderful illustration,all right, referring to that figure in
tertiary adrenal insufficiency, so this isadrenal insufficiency at the hypothalamus,
most often caused by steroids.
What is the expected patternfor your cortisol level, your
ACTH, and your CRH levels?

(36:55):
Can I just tell you what it is?
Because if you're that high, so ifthe dysfunction, this is tertiary
adrenal insufficiency, then you'regonna have low levels across the board.
So you'll have low CRH, lowACTH, and low cortisol levels.
Bingo.
Exactly right.
So your corticotropin releasinghormone, that hormone released by
the hypothalamus, is gonna be low'cause that's where the problem lies.

(37:17):
But also your adrenocorticotropic hormone,that's the ACTH released by the pituitary,
is also going to be low because it's notgetting stimulated by the hypothalamus.
And your cortisol levelis going to be low.
That's released by the adrenalgland, but also not being
stimulated by the pituitary.
So the downstream effects,all low, because the problem

(37:40):
lies at the hypothalamus.
Well done, sir.
One quick caveat, one quick thing I wouldwanna add to that, which I noticed as I
was remembering this, is your aldosteronelevels are low in primary, but they're
usually normal in secondary and tertiary.
So that's something to not be ledastray by, that your aldosterone
levels can be normal, but yourcortisol levels can be low, and that

(38:00):
still means you've got dysfunctionhigher up in secondary and tertiary.
And if you remember from thephysiology days, the aldosterone has
to do with your renin aldosteronesystem and your kidneys and salt.
And that is a communication betweenyour adrenal glands and your kidneys.
And much less to do with anythingpituitary or hypothalamic.
So if the problem is not at the adrenalglands, that portion of your adrenal

(38:24):
cortex will be functioning correctly.
Which is why the aldosterone level willbe 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 imagingthat's going to guide you to exclude all
of the other precipitating diagnoses.
So whatever you need to make surethey don't have some life-threatening

(38:44):
infection or an abdominal infectionor whatever it is you need there.
But also if you are able to identifythe location of the problem.
So if you're able to say, oh, this is asecondary or tertiary abnormality, that
may lead to additional brain imaging.
We're talking things like MRI imagingof the pituitary or MRI imaging
of the hypothalamus in order todiscern what the problem may be.

(39:09):
Things like pituitary hemorrhageor an infiltrative process like
sarcoidosis or damage to the areafrom brain radiation that they've had.
All of those things can cause necrosisin the brain and cause those secondary
or tertiary effects, and that can beordered later by your inpatient team
after you've done a great job savingtheir life and resuscitating them.

(39:30):
Or if they've had a trauma or a surgeryrecently, that may be something you want
to pursue a little bit quicker and sooner.
And also to consider involvingyour neurosurgery colleagues,
especially if it's one of theirpatients, 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'regonna talk about hydrocortisone, right?
As I mentioned before, a million times,we're talking about hydrocortisone.

(39:53):
If you suspect it, you're givingit, and the standard adult dose is
a hundred milligrams intravenously.
If you don't have IV access, itcan be given IM, so don't wait.
If they're critically unstable andyou're already suspecting this, just
give 'em the hydrocortisone IM whileyou're waiting to get IV access and
give it to 'em as soon as possible.
Now, that's just the initial dose.

(40:15):
It is later going to be followed by 200milligrams a day as either a continuous
infusion or as bolus dosing everysix hours at 50 milligrams a piece.
So just know that if they'rehovering in your emergency
department for a long period oftime, they've become more stable.
Maybe they've been downgraded from an ICUbed and they're waiting for a floor bed,

(40:37):
and now they're becoming more unstable.
It's probably because they're due fortheir next dose and you gotta make sure
that that's a priority to be administered.
The pediatric dosing is 50 milligramsper meter squared of body surface area.
And that, again, is given IV orIM, and then followed by either
a continuous infusion or the sameevery six hours divided dosing.

(40:57):
So just know, again, if they're hoveringin your department for a long period
of time, they need that repeat dosing.
And the best medication is hydrocortisone.
Stress dose steroids can alsobe given with other steroids.
So for adults you can givemethylprednisolone 40 milligrams
IV every 24 hours, or it can bePrednisolone 25 milligrams orally,

(41:19):
followed by two additional 25milligram doses in the first 24 hours.
There's multiple different waysto 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 needto fix their fluid status.
So these people are getting fluid boluses.

(41:40):
You're gonna need to fix hypoglycemia.
You may need to add some D5 in there.
And then further treatment becomestailored, depending on their response,
depending on what you find from youradrenal crisis laboratory testing,
and depending on what their subsequentdiagnosis to put them in the adrenal
crisis is eventually elucidated to be.
So you gotta treat their sepsisor their appendicitis, or

(42:02):
whatever it is that occurred toset them in the adrenal crisis.
There are patients who haverecommended sick day dosing.
So they're already on hydrocortisoneat home and when they get sick,
their endocrinologist has educatedthem or the parents that this is
your sick day dosing, meaning we'regoing to double your hydrocortisone.

(42:25):
Typically that's doubled for fever over38 degrees centigrade or tripled for
a fever over 39 degrees centigrade.
And that's continued for theentire duration of the illness.
So if it's a child and they've got a URIand they're spiking fevers, they're just
gonna stay on that stress dose steroid.
You might notice, well, theparents doubled it, but the
patient's not improving.
And it may be just that thefever's gotten so high, they now

(42:47):
qualify for the triple dosing.
So keep that in mind that it may justbe subtherapeutic, even at the doubled
level and that that can be given at home.
And when they fail that and they cometo the emergency department, we're
switching back to hydrocortisone.
There are some patients whogive hydrocortisone IM at home.
Now this is not available yet in anauto-injector, so they're drawing

(43:09):
this up and injecting it themselves.
They may have prefilled syringes at home.
But again, another important pieceof information for our EMS colleagues
to extract from the family, and it'simportant to know when their last dose
was because you're gonna need to repeatit in the ED or in the hospital to make
sure that they're not missing those doses.
I've embraced metric for measurements.

(43:29):
I'm here for that, but I refuseto embrace Celsius temperatures.
So for those like me, 38 celsius is100.4, so they're getting double their
dose if they're over a hundred, andthey're getting triple their dose
if they've hit 39, which is 102.2.
Over 102, they're gettingtriple dose, over a hundred,
they're getting double dose.
For those of us that wanna live andbreathe by my friend Fahrenheit.

(43:52):
. And then there's maintenance therapy.
So typically patients who areon maintenance therapy are
on two different medications.
They're taking hydrocortisone andthey're taking fludrocortisone.
So they're maximizing both theglucocorticoid and the mineralocorticoid
replacement therapy in order to makesure that they're perfectly balanced.
And the dosing is there for youin the article, but most cases,

(44:13):
that's not really gonna apply tous in the emergency department.
We're giving the stress dose, adrenalcrisis 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 recommendedinitial IV dose of hydrocortisone for
pediatric patients in adrenal crisis?

(44:36):
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 50milligrams per meter squared.
So I believe that is not a weight-baseddose, but a surface area based dose.
And I would tell you that my onewalk away from this is, I honestly
need to go look up how do I measurethe surface area of a child?

(44:58):
'cause I don't know thatoff the top of my head.
MD Calc is your friend,
Hey, there you go.
MD calc plug.
Always your friend.
There's always somethingthere to help you calculate.
And there is a calculator forbody surface area in children.
Which of the following actionsshould be taken first when adrenal
crisis is suspected in the ED?

(45:19):
A, await cortisol lab results.
B, consult endocrinology.
C, order abdominal imaging.
D, perform the cosyntropinstimulation test, or E, administer
parental hydrocortisone.
Sorry, I missed the question.
I was looking up the bodysurface area calculator 'cause
I was so excited about it.
You're gonna have to hit me one more time.

(45:39):
Which of the following actionsshould be taken first when adrenal
crisis is suspected in the ED?
What's the first thing you gotta do?
Give IV hydrocortisoneor IM hydrocortisone.
Give the hydrocortisone,do not delay therapy.
Alright, one more question.
100 or 40 of solumedrol ifyou don't have hydrocortisone.
'Cause sometimes I think I talkto pharmacy and they're like,
oh yeah, we'll get that for you,and then it's gonna be a while.

(46:00):
So that'd be something where I'd givepharmacy like, you know, 20 minutes and
then I'm giving them IV, whatever I got.
So if you're the director or if you'reinvolved in administration or if
you're the pharmacy representativefor your physician team in the ED,
this is one of those medicationsyou really want in at least one
Pyxis machine in your department.
Because you don't have the luxuryof waiting an hour for this to come

(46:21):
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 notlikely to get absorbed systemically
in the same manner as it would ifthey 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 reducesyour absorption and is gonna reduce

(46:44):
your serum levels and it's notideal and you're gonna be looking
for something IM, so you want thathydrocortisone available to you for sure.
Okay.
And this speaks to the lastthing that you just mentioned.
For a patient with adrenalinsufficiency who has a fever of 39.5
degrees Celsius, how should theirhydrocortisone dose be adjusted?

(47:05):
Over 102 so you triple it.
There you go.
Triple the dose if they're over 39.
. Alright, let's just talk abouta couple of special populations.
First is pregnancy.
So yes, people with adrenal insufficiencycan become pregnant and when they do, they
still have to continue their medications.
So hydrocortisone is theglucocorticoid of choice and it

(47:27):
is inactivated by the placenta.
So it's not crossing that placentalbarrier, but it's critically important.
And depending on their stage ofpregnancy, they may need increasing
doses as they progress through pregnancy.
And then they may need stressdoses in certain situations.
So during labor a huge stressorand they're gonna need to be on

(47:47):
the full stress dosing there.
If they end up getting aC-section or having surgery,
again, full stress dosing there.
But also early in pregnancy, there'ssignificant overlap between hyperemesis
gravidarum and adrenal crisis becauseof that persistent nausea and vomiting.
And it can be hard to tease it out.
So is this hyperemesis or is thistheir adrenal crisis cropping up again?

(48:10):
And you may need to do some stressdosing around those times as well.
So just understand that there'ssome overlap there and it can
be a little bit confusing.
Not a bad idea to consulttheir OBGYN as well.
'cause they probably havestruggled with this before.
I think that's gonna be our lastingimpression as we finish this thing up
is, you know, do the thing, but then getthe consultant and get them admitted.

(48:30):
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 episodesto our septic shock episode.
And we talked about this extensively.
There is a role for hydrocortisonein patients in septic
shock who were on pressors.
There is actually a mortality benefit.
And that leads me to ourlast two trivia questions.

(48:51):
Alright.
This one's a case, a 38-year-oldwoman presenting with fatigue,
weight loss, and craving salty foods,appears unusually tanned and has labs
revealing low sodium, mildly elevatedpotassium and a glucose in the sixties.
What diagnosis shouldbe strongly considered?

(49:13):
We've got addison's disease,diabetes insipidus, Hashimoto's
thyroiditis, or pheochromocytoma.
She sounds like an Addisoniancrisis to me, and I'm gonna
give her some hydrocortisone.
She is adrenally insufficient.
She's not yet hypotensive, atleast not given in the case.
But absolutely someone who sounds like shehas Addison's disease and you gotta send

(49:36):
off all those labs and give her a littledose of steroids and see how she responds.
And then the final question, which ofthe following is a documented pitfall in
ED management of adrenal insufficiency?
So which one of thesemistakes do we know we make.
Administering fludrocortisone beforelabs, delaying corticosteroids to
confirm diagnosis, overtreating withglucose before cortisol, initiating

(50:03):
vasopressors too early, or administeringhydrocortisone without consent.
Honestly, I think in this case, almostalways, it's you can talk yourself into
something else and you delay givingthe hydrocortisone, and I think this
is a good time to say, you know, couldbe this, could be this, could be this.
So just to cover myself forsome sort of adrenal crisis, I'm

(50:24):
gonna give the steroids and thenI'll let it play out upstairs.
And that, ladies andgentlemen, is it for us.
So the takeaway message being havea 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 accepteddefinition involves the treatment.

(50:47):
So suspicion isn't enough.
And if you think they have thediagnosis, give 'em the hydrocortisone
and see if they respond.
And that's it for our EmergencyMedicine Practice October 2025 article.
Thank you to the Simcoes forauthoring this outstanding
review of adrenal insufficiency.
Keep it in your office inyour little physician lounge.
Keep the article handy.
Keep the references on your phoneand just keep that diagnosis in the

(51:10):
forefront of your brain next time yousee 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 forthis month's episode.
I hope you found iteducational and informative.
Don't forget to go to ebmedicine.netto read the article and claim your CME.

(51:33):
And of course, check out all threeof the journals and the multitude of
resources available to you, both foremergency medicine, pediatric emergency
medicine, and evidence based urgent care.
Until next time, everyone be safe.