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Show Notes

  • What is one (or many) approaches to taper steroids?
    • Pathophysiology: 
      • Prolonged use of steroids suppresses the HPA axis and natural cortisol production by the adrenal glands. 
      • Tapering the exogenous steroids slowly can give the HPA axis a chance to recover.
    • Who? 
      • It depends but consider in patients who have been on steroids >2 weeks or multiple bursts (covered more in steroids episode) and especially when on longer acting glucocorticoids (like prednisone or dexamethasone).
    • How? 
      • Once the longer acting steroid is at a lower dose, one option is to switch patients to an equivalent hydrocortisone dose to continue the taper.
      • The tapering schedule should be adjusted based on the individual’s symptoms and response to the taper.
        • Consider age and baseline functional status
        • Comorbidities
        • Most important: why they were on long term steroids (would tapering exacerbate symptoms of the disease for which they were on steroids for?)
    • Example:  If a patient is taking 10 mg of prednisone for months
      • You can switch them to 40 mg of hydrocortisone split into a morning and afternoon dose.
      • Alternate weaning the morning and afternoon doses in a stepwise fashion.
      • Reach a total daily dose of equal or < 15 mg of hydrocortisone (Expert opinion, different endocrinologist have different practices).
  • Do all patients require a cosyntropin stimulation test (cort stim or stim test)?
    • No. Obtain a AM cortisol level after holding any exogenous steroids for at least 24 hours (longer if you are tapering off from a longer acting steroid).
      • If AM cortisol is >14*-18 mcg/dL, adrenal insufficiency can be ruled out and steroids may be discontinued.
      • If AM cortisol is >3 but <14*-18 mcg/dl and adrenal insufficiency is suspect, perform a cosyntropin stimulation test.
      • If AM cortisol is <3 mcg/dL in a patient with symptoms of adrenal insufficiency, a cosyntropin test is not necessary to make a diagnosis of adrenal insufficiency due to long term steroid use.
  • What does the cosyntropin stimulation test?
      • What? 
        • Cort stim test asks by giving synthetic ACTH aka cosyntropin, will the adrenal glands respond appropriately in producing cortisol? 
        • After the HPA axis was suppressed with prolonged steroids, the adrenals may have atrophied and may still not be able to make cortisol.
      • How?
        • Baseline blood sample: ACTH and cortisol levels are measured. It is ideal to obtain these in the morning when hormones are at peak levels.
        • Administration of cosyntropin: Cosyntropin can be given IM or IV.
        • Post-stimulation blood sample: Repeat ACTH and cortisol levels at 30 and 60 minutes.
          • The post-stimulation cortisol level indicates the adrenal response to ACTH.
  • How do I interpret the post-stimulation cortisol level after giving synthetic ACTH aka cosyntropin?
      •  > 14*-18 mcg/dL, it is safe to discontinue steroids
      • <18 mcg/dl (or <14 mcg/dl in newer assays), adrenals did not respond appropriately and may need a longer taper 
    • Symptoms:
      • Non-specific symptoms, such as fatigue, nausea, dizziness, GI upset, anxiety, depression
    • What’s the difference between steroid withdrawal and chronic adrenal insufficiency? 
      • Both have similar symptoms
      • In steroid withdrawal syndrome, the cosyntropin stimulation test will be normal, demonstrating a functioning HPA axis and not adrenally insufficient.
    • What do I do? 
      • Explore other etiologies of potential fatigue and other non-specific symptoms including vitamin D deficiency, iron deficiency, hypothyroidism, low testosterone, etc.
    •  

Transcript

Dr. Shreya Trivedi: Hey, everyone! As promised on the last 5 Pearls episode on steroids, here is the bonus with Dr. Shariff. She had a really easy way to understand cosyntropin stimulation tests also known as cort stim test or ACTH stimulation tests but we just couldn’t fit it in the original steroids episode. So when I sat down with Dr. Shariff we talked about 1) what is a cort stim test is and what exactly is it testing 2) how to interpret the results, and 3) how to tell the difference between steroid withdrawal and adrenal insufficiency. And to get us into that headspace, let’s first do a quick of throwback to steroid tapers, acknowledging what Dr. Shariff said on the last episode, that if you ask 5 different endocrinologists, you’ll get 10 different answers of how to do steroid tapers.

Dr. Afreen Shariff: What is, what is your approach to, steroid tapers?Anecdotally, what has worked for me and physiologically what makes most sense is to get patients to hydrocortisone and then taper them off to get them down to lower than physiologic dose, and then test them for their ability to make their steroids naturally on their own. So, for example, if someone comes in on say, 10 milligrams of prednisone, who has been on it for several months and now they require steroid taper, what I end up doing is switching them over to a dose equivalent switch of hydrocortisone, and then stepping down that dose gradually, depending on how long they’ve been on steroids. So let’s say they’ve been on steroids for five months, then the steroid taper can be done a little quicker compared to someone who’s been on it for say, two years or has other comorbidities that could complicate your assessment of the steroid taper. So then, I typically end up doing a step down approach where I start first with the morning dose, dropping the morning dose, and then step down the afternoon dose, then step down the morning, dose, then the afternoon, and keep going that way until I reach a dose of five milligrams or less of hydrocortisone. And then have the patient hold their dose a couple days before they do their actual cosyntropin stimulation test. And that seems to have worked for a majority of my patients, especially the ones that require I say a gentle taper, this seems to work more seamlessly. And physiologically it makes more sense cause prednisone is a longer acting steroid and has more chances of suppressing the HPA axis that you’re actually actively trying to wake up by doing your taper. So it makes sense to switch them over to a shorter acting, um, steroid that wears off overnight and then you have time for that HPA axis to wake up in the morning, and take on that next step on the taper dose.

Dr. Shreya Trivedi: And just to pause real quick and be explicit, why are we having our patients hold their steroids and do the cosyntropin stimulation test? Well, the cort stim is used to check for adrenal insufficiency and how much of the hypothalamic-pituitary-adrenal axis, the HPA axis, has been affected by being on steroids. Now I will say, sometimes can get away with an AM cortisol, if its < 3 mcg/dl or 5 mcg/dl its very specific for adrenal insufficiency but there some nuance to interpreting the AM cortisol. We talked about this back in 2018 on our adrenal insufficiency episode. But if you can’t get away with just an AM cortisol, the cort stim test, on the other hand, is very sensitive to picking up adrenal insufficiency. Do you always do a cort stim after, with all tapers or, or is it just kind of your patients who were a concerned for adrenal insufficiency? I’m curious your practice on that?

Dr. Afreen Shariff: Yeah! Depends on how long they’ve been on steroids, right? So if it’s been a short taper, um, and usually people don’t come to endocrinologists if they’ve been on like you know, five days of steroids, right? So we’re talking people who need assistance getting out of steroids cause they’ve been on it for stable bone marrow transplants. They’ve been on it for RA or lupus for a very long time, and now they’re on steroid-sparing agents and their rheumatologist or pulmonologist has said, okay, they can get off of steroids. We need some help. So we’re not usually seeing the ones that are easy tapers. So when they come to us, they’ve been on steroids for a while. And that’s the assumption. So when we try to taper these folks off, we do end up doing cosyntrophin stimulation test cause that really puts us in a place that we can make a decision if the patient can, number one, be off with steroids, should be worried about an adrenal crisis if say they have a flu or a covid infection. Right? Do we know that the HPA axis is woken up enough that it would respond to it? So, yes, in our practice, because of the patient population that we see, we do end up doing cosyntrophin stimulation tests at the end of every steroid taper.

Dr. Shreya Trivedi: Can you just explain, for people who haven’t thought of the cosyntrophin test for a while, what exactly it is and um, what exactly you’re looking for with the 14 versus the greater than 18?

Dr. Afreen Shariff: Absolutely! So this is a common test that we end up doing, um, in endocrine, right? In endocrine we’re very convoluted, I say. When we are looking for deficiency, we like to stimulate you and we’re looking for excessive hormones, we like to suppress you, right? So that’s the basic ideology and the concept that we go with, right? And we’re all about pathways and how folks are responding. So if you wanna understand about how ACTH and cortisol are kind of cross-talking to each other, you think of the pituitary gland that’s sending an email in the form of ACTH telling the adrenal glands, which are sitting right on top of the kidneys to make that end hormone, which is cortisol, right? So when we have patients, let’s say long-term steroids, so we are causing tertiary adrenal insufficiency where we’re shutting down that HPA axis, so hypothalamic pituitary adrenal axis. So we’re shutting that down. So we suspect that under the influence of the steroids, your ACTH is low, and your cortisol is low.

Dr. Shreya Trivedi: To review just one more to make sure we all have this, the part of the HPA axis we need to know is the pituitary gland produces ACTH, which then goes down and tells the adrenals to produce cortisol. Long term steroids suppresses that whole HPA axis.

Dr. Afreen Shariff: So when we do our steroid tapers and we want to do, say a cosyntrophin test to determine if the patient can respond, what we’re trying to do is we’re trying to give a nice horse kick to the adrenal gland to make it wake up and bring it back from where they’re vacationing in Hawaii, back to making some steroids. Right? Cause that’s what the body understands. If I’m taking prednisone or hydrocortisone for say, five months, the adrenal glands, the way they respond is that, ‘Hey, I’m not needed. I can go vacation in Hawaii cause someone else is doing my job.’ And you know how hard it is to come back from vacation. That’s exactly why we do a taper. We try to ask them to come back, send them some flowers, send them some chocolate, and say, ‘Hey, you gotta come back over here and start acting.’ Right? So at the end of these tapers, that is what we’re doing. We’re giving a horse cake in the form of an ACTH shot. So cosyntrophin is nothing but synthetic, ACTH, that is given in the form of an intramuscular shot typically cause it’s given in clinic and we get labs done at time zero. We like to do it at eight o’clock in the morning. Again, we’re not held onto that timing, depending on when your patient comes in and how far they live. Right? So ideally 8:00 AM in the morning cause you want to see at the peak time what your cortisol and ACTH at baseline are. And then the patient gets that shot, they wait in the waiting room for about 60 minutes, go back down to the lab, get the post-stimulation cortisol done, which is after 60 minutes. And people do it differently. They do 30 minutes and 60 minutes. We typically end up doing 60 minutes and what we see is the relative difference between the pre and the post cortisol. And the numbers you want to hit is above 14 for the post stimulation cortisol, which is very reassuring. And then above 18 is absolutely reassuring.

Dr. Shreya Trivedi:  So just a quick recap! When we give synthetic ACTH, or cosyntrophin, we can then see if the adrenals are working the way they should by measuring the cortisol levels 30 and 60 mins afterwards. The numbers you want to look for is cortisol to above 18mcg/dl. Now I will say the newer assays the cutoff is 14mcg/dl. Either way, the higher the better!

Dr. Afreen Shariff: From a patient perspective, if I’ve done a taper. And I’ve been off of steroids and I’ve done a cosyntrophin test and my post stimulation cortisol is 19, 20, I’m in the blue. I’m doing very well. I can be off of steroids. You get a blessing from the endocrinologist and you say, everything’s fine. Call me if you need me. Don’t throw away your steroids just in case, and just hang on to that and here’s my number. Right? Now, if someone comes back with a post stimulation, cortisol as 14, they’re still not, um, out of, out of danger, right? You’d wanna reconsider, do I need to again, do a taper or do I want to wait, watch and repeat the cosyntropin test in a couple weeks or one week? Right? And again, everyone does it differently. If I do a stim test and someone comes back with a cortisol of seven. They, so they went from five to seven. I know that those adrenal glands have not woken up, right? That is a patient that either may need lifelong steroids or can get off of steroids in the future with a slower taper. And if it’s someone who’s 80 years old with multiple comorbidities, I’d rather say, ‘We’re gonna keep you on steroids, very low dose steroids, quality of life matters. We’re not gonna go through this, um, experience again.’ So really at that point, it comes back to the discussion of who would be an okay candidate to leave on steroids versus would you like to attempt to get off of steroids? Cause now they’re 40 years old and they have a long life ahead. Right. So it really depends on those factors. 

Dr. Shreya Trivedi: You know, this made me think a lot about steroid withdrawal syndrome that we talked about in our last episode! And how it differs from adrenal insufficiency. With steroid withdrawal symptoms a patient typically feels fatigued, nauseous, dizzy, GI upset, depressed, But, they are not adrenally insufficient! But, when I think about it, those symptoms of steroid withdrawal syndrome sound very similar to chronic adrenal insufficiency. Both of them kind of make you feel like crap! So, I asked Dr. Shariff how she tells the difference. Cause now that I understand cort stim test more, it sounds like we have some objective guidance here, right? If our patient is still just not feeling great, but their cortisol level comes back greater than 18 mcg/dl, maybe we can clearly tell them ‘Hey, you’re not adrenally insufficient’ and the steroid withdrawal syndrome and something else. I asked her if that thinking is correct! 

Dr. Afreen Shariff: So with endocrine, one good thing is that we don’t have a lot of vague things in endocrine, which is a good thing, right? So you can quack like a duck. You can walk like a duck. But if the labs tell me it’s not a duck, it’s not a duck, right? So that’s how we look at it in endocrine. It’s, it’s, it’s not black and white, of course everything’s not black and white, but we’re more closer towards that. More so than, say, specialties that are more driven by symptomatology, right? So we have lab work. We rely heavily on that and. Oftentimes, if I’m getting absolutely normal cosyntrophin stimulation tests and the patient still has multiple complaints of fatigue, ‘I have this, I have that. I’m not feeling really good.’ I’m talking to them about the fact that your symptoms are real. The answer is not an adrenal insufficiency, cause we’ve proven with multiple tests that this seems to be working very well and that’s what the body reads as a barcode, right? So the body is translating that and understanding those levels and doing things according to that. So the levels are fine. That’s how your body’s responding. And yes, is fatigue a million dollar diagnosis? Absolutely. You can go from your hair to your toenails and you’ll have a specialist tell you a big differential in what fatigue is. So at that point, I’m really thinking about is there other hormone abnormalities that I can fix? Right? Is there, say vitamin D deficiency. Is there iron deficiency? Are we talking about, um, hypothyroidism? Are they on thyroid replacement already? Should that be optimized? Are they an older gentleman and is this low testosterone? Right? So these are the kind of things I’m exploring in patients and trying to kind of go down that list rather than pinning, uh, the tail on adrenal insufficiency within normal cosyntrophin stimulation tests, right? So the labs are telling me this is normal, everything’s fine. Patients still has complaints. Patient’s symptoms are real, but it’s not coming from adrenal insufficiency. That’s the kind of discussion I end up having. And it’s easier to have that sort of discussion when the patient is coming to see a subspecialist, cause the buck kind of stops with us. Right? So it’s a harder discussion to have, say, at other specialties because they may not have extended the testing to that point. Right? So it’s where they’re having that discussion.

Dr. Shreya Trivedi: Yeah, that’s a, that’s a good point. Um. So interesting. Makes me want to do like a adrenal insufficiency 2.0 episode, actually.

Dr. Afreen Shariff: Do, do you wanna do an endocrine fellowship? We can totally recruit you!

Dr. Shreya Trivedi: I know, that’d be so fun! Haha, okay, that was a wishful thought while that lasted. I’m happy being an internist. Okay, so let me try to summarize what we’ve learned. When doing a steroid taper, there’s tons of ways to do it, but as we learned in the steroids episode, hydrocortisone is a short acting and a physiologic analog, and that can be helpful in waking up the adrenals. A cort stim test can be helpful to test the adrenals. If cortisol level 30 to 60 mins after injecting synthetic ACTH or cosyntropin is less than 14*- 18 mcg/dl (depending on the assay), then we know the adrenals have not sufficiency woken up during that steroid taper. If, however, the cort stim test result is greater than 14-18* (depending on the assay), but the patient is still fatigued, nauseous, dizzy, having some GI symptoms, just not feeling great, then we can say this is not adrenal insufficiency, and may be steroid withdrawal syndrome or we can look into a broader differential for other things that can come with fatigue!

Dr. Shreya Trivedi: And that’s a wrap for this bonus episode! If you enjoyed this bonus episode and want to help pick out more bonus content share, send us an email and come join the Core IM team. We do tons of interviews and have content that doesn’t end up making it on air, but is still gold! Thank you again to everyone that made this episode possible, particularly Dr. Sam Woodworth for the accompanying graphic, as well as toand Dr. Tina Phan for the show notes. Thank you, everyone and see you next Wednesday! Take care!

References

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