Having elevated cortisol levels can lead to a variety of side effects, and it may impact people with diabetes in a number of ways. Natalie J. Bellini DNP, FNP-BC, BC-ADM, CDCES joined The Huddle to talk about hypercortisolism, how it is diagnosed, and its potential effects on type 2 diabetes management. This episode is sponsored by Corcept. Learn more about Corcept here: Corcept Therapeutics View a recorded webinar that dives deeper into cortisol levels and diabetes management (sponsored by Corcept): A Closer Look at Difficult-to-Manage Diabetes – Is Cortisol at Play? Learn more about the CATALYST study: Corcept Announces Presentation of Results From Prevalence Phase of CATALYST Clinical Trial at American Diabetes Association’s Scientific Sessions – Corcept Therapeutics, Incorporated
Having elevated cortisol levels can lead to a variety of side effects, and it may impact people with diabetes in a number of ways. Natalie J. Bellini DNP, FNP-BC, BC-ADM, CDCES joined The Huddle to talk about hypercortisolism, how it is diagnosed, and its potential effects on type 2 diabetes management. This episode is sponsored by Corcept.
Learn more about Corcept here: Corcept Therapeutics
View a recorded webinar that dives deeper into cortisol levels and diabetes management (sponsored by Corcept): A Closer Look at Difficult-to-Manage Diabetes – Is Cortisol at Play?
Learn more about the CATALYST study: Corcept Announces Presentation of Results From Prevalence Phase of CATALYST Clinical Trial at American Diabetes Association’s Scientific Sessions – Corcept Therapeutics, Incorporated
Jodi Lavin-Tompkins
Hello and welcome to ADCES's podcast, “The Huddle: Conversations with the diabetes care team”. In each episode, we speak with guests from across the diabetes care space to bring you perspectives, issues, and updates that elevate your role, inform your practice, and ignite your passion. I'm Jodi Lavin-Tompkins, the Director of Accreditation and Content Development at the Association of Diabetes Care and Education Specialists. I would like to acknowledge Corcept support for this podcast.
My guest today is Dr. Natalie Bellini. She's an assistant professor of medicine, program director of diabetes technology, diabetes and metabolic care center, and a nurse practitioner at Case Western Reserve University Hospital. We're going to discuss challenging type two diabetes cases and the role hypercortisolism plays. Welcome, Natalie.
Natalie Bellini
Thank you so much. I'm so excited to be here.
Jodi
So before we jump into the topic, Natalie, could you tell the audience a bit more about yourself and your background as it relates to today's topic?
Natalie
Absolutely. So I have been a certified diabetes care and education specialist for many, many years. I actually took written exams every, what was it, five years? Every five years for lots of years before they became electronic even. And I was a nurse before I became a nurse practitioner. And now I am based out of Cleveland, Ohio. I see patients three to four days a week, and I see lots of patients with both type 1 and type 2 diabetes, and some of them are very difficult to treat.
Jodi
Yes, and I think this topic is relatively new, especially to me, so it may be to some of our listeners. Can you help us understand the context of cortisol and diabetes more?
Natalie
Absolutely. You know, we used to think, if you close your eyes and think back to your nursing or NP or RD or any of the medical textbooks, you can picture that person that was illustrated as part of what hypercortisolism or Cushing's disease looked like. And that's what we all learned, that it was a very rare disease, that it was something that you saw once or twice in a lifetime. That's what we would think about. And a lot has changed around that. And what we now know, that lots of people actually have hypercortisolism and that person in your brain, in your textbook actually had hypercortisolism for years and years and years that was untreated. So our challenge is to start looking at it a little bit differently and thinking about it earlier in the disease process when we are managing diabetes.
Jodi
Okay, Natalie, so if this is present more than we realize, I think there may be some long-term clinical ramifications of having elevated cortisol levels that would be great if you could share with our audience.
Natalie
So think about having elevated cortisol levels as the person that might present as having to take steroids for long-term, right? Long-term use of steroids. So those same side effects, it can affect bone health, it can affect depression, it can affect weight gain. It can make managing your diabetes more difficult. It can affect blood pressure and it overall reduces life expectancy significantly. It causes heart attacks and strokes, just like diabetes does.
Jodi
So it sounds like this pathophysiology of hypercortisolism may be a factor in making it hard to reach glycemic targets. So can you say a little more about that? What do you see in your practice?
Natalie
So when we started to think about this, it was, why aren't some people responders to medications that they should be? Right? Why is it that some people, even if we put them on the highest strengths of the GLP-1 or GLP-GIP agonists, right? Why aren't they responding to, they're on higher doses of insulin, they're on an SGLT-2 inhibitor and metformin and maybe even an insulin sensitizer, and we just can't drive those glucoses down or they need so much insulin to get there. Those are the difficult to treat. They don't respond the same way. What else could be going on?
A lot of times these people also tend to have, not always though, high blood pressure that is on two or three medications and they still, you know, they're not the people that are just high when they walk in the door. They're high all the time. You know, even at home they're high and they're on three medications and they're still not at goal and we know they're taking all their drugs. That is difficult to treat. Those are the people we should start thinking, what else is happening here?
Jodi
So how is this diagnosed? Tell me, you know, what tests need to be ordered or how we should be looking at this and figuring out if they have this condition?
Natalie
What we do is what's called a dexamethasone suppression test. We want to suppress that cortisol production. So we prescribe one milligram dose of dexamethasone. It's a pill. The person is instructed to take it at approximately 11 pm at night, between 10 and 11, go directly to sleep. And then wake up in the morning, don't eat or drink, go straight to the lab and we tell people before 9 am, although it's before 10 am, we want a morning cortisol level to see if we can suppress that cortisol level. If we can't, we know that that is a sign that they could have this Cushing’s syndrome, right?
Now, we also draw at that same time a dexamethasone level, how much dexamethasone is actually in their bloodstream from that pill. Some people digest that pill more quickly, and so I need to make sure that they have enough dexamethasone to suppress it. Okay? So there's two parts to the test. They take the pill and I draw two labs. One is a morning cortisol, and the second one is a dexamethasone level. Sometimes people metabolize things very quickly. And those people, they won't get that, one milligram isn't enough and we have to have them repeat the test, right? And take a little bit higher dose of that dexamethasone. So what we're looking for is that that cortisol level is actually low. We want it to be low. And if it's not low, if it doesn't pass the threshold, we actually do the screening again, much like blood pressure. If someone has a high blood pressure one time and I'm in an office, we don't say this person has hypertension, do we? We repeat that, right? Is it just because you're in an office? Is it just because, right?
We want to make sure before we do something about it. Before we start medicating someone. It's the same with this dexamethasone suppression. We'll do it a second time. You know, our office tends to do four to six weeks later, making sure something else isn't involved to double check that this is what's happening. So that's how we look at it. And one of the things I think we should stop, why are we talking about this now? Many of you listening to this podcast heard about the catalyst study that was read out at the ADA this year. And the catalyst study looked at patients with type 2 diabetes with what they called “difficult to treat diabetes”. And what that meant was an A1C, and I think this is surprising, above 7.5, right?
Jodi
Oh boy.
Natalie
I know. I mean, like, well, difficult to treat? Sometimes I’m having a party at 7.5, right? They’re people that are above 7.5, though, that are on multiple medications, right? It isn't like, “oh, you've started metformin and you're still above 7.5”. That's not difficult to treat. That's needing another medication, right? So we want to make sure that we understand that these people are on multiple medications, and that their glucoses were still high. And what they found was 24% of those people actually had high cortisol levels with a dexamethasone suppression test. Not this rare disease that is like only heard of once in a while. You'll see it a couple of times in your career.
You know, those very low numbers that we've read about in the past. That this is actually probably more common than we ever, ever thought. So they found that 24% of individuals had hypercortisolism. And that's why we're talking about this today. That it's a different disease. You know, it was kind of like when the first GLP-1s came out and we're like, “oh this is nifty. This is another medication to treat diabetes.” And then we realized, wow, this reduces your risk of cardiovascular disease and this does all these other things, right, as we line those up. This is like that. It's like, okay, now we recognize that lots of people, one in four, have this hypercortisolism. Now there's this follow-up study to see what are we going to do about that? What are we going to do following that? And so, people with hypercortisolism can have that extra cortisol being secreted a couple of different ways. And so we then do further testing. And that's when really endocrinology gets involved.
So if you're in primary care and you diagnose someone with hypercortisolism, you've done this testing, you're stopping there pretty much, and sending them to endo that will then decide what to do. Because we need to know if it's coming from the adrenal glands, is it coming from pituitary, and what to do about that. And for most people, that is beyond their regular clinical practice. What we need people doing is screening for it and then sending on to care, much like you do an EKG, you know, in your office as part of a yearly physical. If that EKG is abnormal, most people are sending those people on to cardiology. They're not making clinical decisions beyond that. We should be thinking about it that way, just like we would send someone to podiatry who is struggling with feelings in the bottom of their feet to get fitted for shoes. I don't fit people for shoes in my office, right? So we need to think about this as, we as clinicians are part of the screening continuity of care, right? We're screening and then sending on to experts for a lot of us.
Jodi
Yeah, and that's a really good point. And I want to ask you, what about the diabetes care and education specialists? So, with the people that they're seeing in their office or their clinic or through telehealth or whatever means they're seeing people, what should they be looking for? And do you think there's a person you can think of who can bring this kind of to life for us with sort of a case study example? I learn better if I can picture the person, and what to look for and then know the next steps.
Natalie
Absolutely. So, the first thing we do is say, all right, let's think about this as diabetes care and education specialists. And remember, you know, that is such a gamut. We have psychologists, dietitians, RDs, RNs, NPs, PAs. We have such a gamut, MDs. We have a gamut in our listening audience. I think that we are one of the most diverse groups there are out there. So it's going to depend on the clinician. But no matter who is sitting in front of you, person is sitting in front of you and you're just like, okay, wait a minute. Our biggest first one was they don't respond to these very strong once weekly GLP or GIP agonists. Their glucoses don't come down as we expect. Metformin didn't seem to do anything. We expect metformin to drop an A1C one to one and a half percent with newly diagnosed. And they're just like, it's just been this long arduous, like we keep adding medications and nothing is working.
The first thing I would do is say, “are they taking the medication?” So you want to, and I apologize for excluding our pharmacists, our pharmacists are such a big part of ADCES. Make sure the patient is actually taking the medications, obviously. But the dexamethasone suppression test is an easy test. Like there's not a side effect from that for anything. So it's not like you're suggesting something that will hurt the patient or there's a whole lot of risk. And sometimes I'll even do it, you know, it doesn't have to be done today. This is not an urgent thing, but it's important. How's that for a priority? So I'll say, you know what, you need labs in three months. We're going to add this test. I have a handout for them and I instruct them how to do it. If you are not a prescriber, you can just put this in your note and say, you know, you can quote the catalyst study. I mean, I did that yesterday when I had to write a letter of medical necessity for someone. I quoted the ADA guidelines. And the beautiful thing about this is if we can treat that hypercortisolism, people actually need less medication.
You know, there's some depression in this. They'll say, “I have this underlying depression. My blood pressure is always a little bit elevated”, even though they're on three medications and you feel like they really are doing what you're asking them to do. Weight loss is just very difficult. They go down a pound, they go up two, they go down three pounds, that kind of thing. They lose a little bit, but not what you would expect. That's that person, right? I had someone that recently actually, she presented in this exact way. She was on trisepatide at 12 and a half. She couldn't tolerate that last dose, right? She's on full dose of metformin, an SGLT-2 inhibitor, 78 units of basal insulin a day. 15 units at every meal plus a pretty heavy sliding scale. On top of that, 20 units when she ate a larger meal.
So that's true insulin resistance. It's all of it together. Her blood pressure was always a little bit up. She's on all kinds of blood pressure medicines. That's that person. The challenge is you could also take away the blood pressure altogether and she could have a normal blood pressure and still I would screen her at this point for hypercortisolism.
So those are the people that you just go, “huh, things aren't working”. And so why is it taking more medication for this person than the average person? And some people are just more insulin resistant, but maybe they're not really more insulin resistant. Maybe we've missed a diagnosis. So this person actually, what we do is, we do a scan of the adrenals and look at, this person had an adenoma on one of her adrenals. They removed the adenoma, and everything got better. She felt better. Right? So there are ways that we can treat this. You know, and it's not just a little bit of surgery, but we have to take it off. We can remove it and make it better. There are also medications we can use, oral medications that we can use to treat the underlying problems.
Jodi
And so you went forward with the adrenal scan because of her dexamethasone suppression test results.
Natalie
Yep.
Jodi
Okay.
Natalie
And that's what we did, right? So the suppression test was positive twice. Now, at our institution, we have someone that is an expert, an endocrinologist that's an expert in this. And he actually took the case over with the fellows at that point. They arranged the, it's what we call a neuroendocrine disease. The surgeon removed the problem on that adrenal gland. They remove it. And so they still have another one on the other side. So now we don't have this extra cortisol expression. And so things got better. We needed much less drug. We need much less. And it's, the most amazing thing, is the people that we treat say, “oh my gosh, I feel so much better. I didn't know how depressed I was. I didn't know how sluggish I felt”. Because they don't know how bad they feel because what we know about Cushing’s syndrome is it's a long, slow thing. It's not overnight, all of a sudden you ended up with Cushing's.
So these people have had problems for a number of years because we don't see them until they develop diabetes from this hypercortisolism. Think about it that way. Much like type 2, we don't see them for a long time if they haven't been screened, and all of a sudden they're there with high glucoses. But it didn't start the day before you saw them. You know, it's a disease process just like diabetes is.
Jodi
Sure, and using that case, the example that you gave us, that woman you talked about, what kind of conversation did you have? Like, what would a conversation look like with someone you suspect has hypercortisolism driving their disease?
Jodi
So, I think with other screening, we don't want to overwhelm someone. So just like with cholesterol screening, we say, high cholesterol can increase your risk of heart attacks and strokes. So we want to manage your cholesterol, your blood pressure, your glucose in order to reduce that risk. Each individual part of that does that. I want to screen for something called Cushing's to make sure that we're not missing something else. You know, Cushing's can cause you to have struggles with weight loss, struggles with managing your diabetes or your blood pressure. And I just want to make sure. So we're going to do this test and we have a tear off sheet that we use. And then I explain what dexamethasone suppression tests, the expected results. Because it comes up, you know, we use Epic in our practice and I'll say, what I want is that level of cortisol to be red. I want it to be low. So if it comes up low, that's a good thing.
I explain what we're looking for. And so that they're not alarmed. And then once they do the test, I pick up the phone and say, “look, this was normal or this was abnormal and this is what we're doing”. I don't get into the, “well, then we're going to have to do a scan of your adrenals and then we're going to have to see…”, you know, I don't do all that just like we don't do that with cholesterol. So I keep it pretty basic in the beginning. And then we go from there because I think that we don't want to scare people. It's like, when you go for a mammogram, do you think about, well if I have a lump, is it going to be stage one or two or three? Or what's gonna happen and what about lymph nodes, you don't talk about that, right? You talk about the real things, which is, “you know what, you're on three or four diabetes medications, we're still not at goal, I wanna do a test to make sure we're not missing something else”.
Jodi
Yeah, keep it simple.
Natalie
Right? Yeah.
Jodi
Well, Natalie, this has been great, I've learned a lot through this conversation and I'm wondering if you have any closing thoughts for our listeners.
Natalie
I think what we need to remember is that diabetes, for those of you who have been practicing for a while, think about what we used to do. We used to look at a finger stick in the morning and we'd make changes to insulin throughout the day. And then we had CGM and now we're like, “oh I can't even look at someone that doesn't use a CGM”. And then we had GLP-1 and we're like, “oh yeah, once in a while we might use that”. Now it's part of the standard of care. And then we had SGLT-2s and we're using that in the hospital for heart failure, for goodness sake. We had no idea what that medication, that class of medications did. We may now look at the screening for Cushing's as part of our clinical practice. We should be doing it if we can, personally as a clinician, or recommending the screening as a clinician that isn't able to actually write the orders and feel comfortable about why we're doing it. The study that this is about, that why we're having this discussion is called Catalyst. And I think that every one of us needs to recognize that screening for Cushing's is going to now be part of our clinical practice. And I think long term, the ADA guidelines, we should expect in the next several years to change to make that happen.
Jodi
Right. I want to thank you, Natalie, for sharing your expertise on this topic with us. This may be newer information for some of our listeners, and I think it's important to discuss. And again, I would like to acknowledge Corcept's support for this podcast.
Thank you for listening to this episode of The Huddle. Make sure to download the resources discussed on today's episode. You can find them linked in the show notes. And remember, being an ADCES member gets you access to many resources, education, and networking opportunities. Learn about the many benefits of ADCES membership at adces.org/join. The information in this podcast is for informational purposes only and may not be appropriate or applicable for your individual circumstances. This podcast does not provide medical or professional advice and is not a substitute for consultation with a health care professional. Please consult your health care professional for any medical questions.