Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered Podcast. I'm Dr Neha Pathak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine. A lot of us have heard about the impacts of high cortisol in the context of stress, but Cushing’s syndrome is something very different. It's a pathologic cortisol excess that can quietly drive serious health problems like high blood pressure, diabetes, osteoporosis, mood changes, abnormal cholesterol, and often changes in the way that we look, sometimes long before anyone connects the dots.
You might remember in 2024 when fans encouraged comedian Amy Schumer to seek advice from a healthcare provider after they unexpectedly and correctly noticed that she had Cushing’s syndrome. Now, here's the tricky part: not everyone will have the classic look of Cushing’s syndrome, and many of the symptoms can be common due to other life changes, for example midlife weight changes or high blood pressure as we age.
That's why today's conversation matters. We talk about what cortisol is supposed to do, what Cushing’s syndrome really means, why diagnosis is often delayed, and what practical steps you can take if you suspect something more than everyday stress is going on.
We're also going to explore a topic that I'm sure many listeners will relate to, something that goes beyond Cushing’s syndrome: the experience of knowing that something is wrong with your health and feeling dismissed or unheard by your healthcare provider. We'll talk about what to do in these situations to feel empowered and engaged in shared decision-making and how to avoid being diverted from proactively caring for your health by medical mistrust.
First, let me introduce my guest, Dr Lewis Blevins. Dr Blevins is a neuroendocrinologist specializing in pituitary and hypothalamic disorders, along with various adrenal conditions. As medical director of the California Center for Pituitary Disorders at UCSF Medical Center, he guides a team providing comprehensive state-of-the-art care.
He has a special interest in Cushing’s syndrome, also known as hypercortisolism, and has edited a book on the subject and written a book on the topic directed toward patients and physicians. Welcome to the WebMD Health Discovered Podcast.

Lewis Blevins, MD: Thank you very much. It's my pleasure to join you today for this discussion.

Pathak: Well, I am very interested in our topic for today, but before we jump in, I'd love to start by asking you about your own health discovery, particularly as it relates to your work with Cushing’s syndrome.

Blevins: Well, that's, um, a topic that we could talk about for hours and hours, actually. I think that my own discovery and interest in this condition came even before my fellowship, when I would see people who looked Cushing’soid, so to speak, as they were given high-dose steroid medications. And I remember being taught that if you ever see this in a patient who's not on steroids, you should think about endogenous Cushing’s syndrome due to either a pituitary gland problem or an adrenal gland problem.
And that fascinated me, that we had drugs that we used to treat different conditions that could actually cause a syndrome that resembled disease. It didn't seem like that was necessarily a good thing for patients, to have a treatment that could do something that caused all the same symptoms and signs as a bona fide disorder that was related to tumors.
So I became interested at that stage early in my career, and then in fellowship gained exposure to people who had bona fide Cushing’s due to pituitary disease and adrenal disorders, and just developed this deep fascination in that particular topic.

Pathak: I'm really curious. Let's take a step back because I think a lot of people hear about the ill effects of high cortisol, so they recognize that cortisol, if there's too much in your system, that can be a problem. So help us understand Cushing’s syndrome in the landscape of other things that might elevate cortisol.

Blevins: Well, let's first talk about semantics. Cushing’s syndrome is the condition that's named after a constellation of symptoms and signs that mimic a case report by Harvey Cushing’s in the early 1900s. In 1912, I think, was his first publication. He published her case in a book in 1914, and since he gave the first description of that, there probably were others describing it at the same time, but the name was given to honor him for that description.
So people who tend to look like that are said to have Cushing’s syndrome, and they often have a rounded face, reddened face, proximal muscle weakness, and decreased muscle mass and increased fat, especially in the abdomen, above the collarbone, and on the back of the neck, to where they look Cushing’soid.
The term Cushing’s disease was then sort of used to describe people who had the same appearance of Cushing’s syndrome but had a pituitary tumor. So Cushing’s disease is a pituitary adenoma causing the problem. Cushing’s syndrome is anybody with a problem, and also the term used to describe people that have Cushing’s disease. We have other terms we call ACTH-dependent or independent, depending on whether it's pituitary or ectopic ACTH or adrenal disease.
One of the things that we've learned, however, is that not everybody with this condition looks like that. So it's sort of a misnomer, if you will, to call it that. And I think that we need to be thinking forward about other ways to describe this syndrome so that patients can be recognized sooner rather than later by primary care physicians and others who are on the front lines of medicine. I like to think of all of these patients as having what I call pathologic cortisol secretion, where cortisol secretion is abnormal for one reason or another.
And it's the high levels of cortisol that cause the symptoms and signs, which also include other things like hypertension, diabetes mellitus, osteoporosis, depression, anxiety, et cetera. But it really — I guess I used to be a lumper, now I'm a splitter. I think we need to be specific about what we're talking about so that we can converse and you can be specific about doing research projects and looking things up on the internet and all of that.
But in summary, it's this conundrum of symptoms and signs, some of them hidden, some obvious, that are due to cortisol excess, whether that's produced by the adrenal glands or steroid excess by a drug that someone is taking to treat another disorder.
Before we get into diagnosis, just help us understand what cortisol is meant to do in your body, and then we'll get into diagnosing when there's an excess of cortisol.
One of the things that I tell my patients is that cortisol is thought best of as a stress hormone, but you could think of it as the operating system of a computer, where it's doing all sorts of different things to help your body deal with normal physiology, stressed physiology, and things of that nature.
It regulates a number of processes, including the production of glucose from the liver and from muscle. If we need glucose that's stored in our body in some way, if we need it to be readily available. It maintains the contractility, or the forcefulness, of the heartbeat — the heart rate. It probably modulates our central nervous system function in ways that we don't fully understand, and certainly our sympathetic nervous system, because it's involved in the production of epinephrine by the adrenal glands.
It's a hormone that, I guess it's easiest to say that it tamps down the immune response. If we didn't have cortisol when we were sick with the flu or COVID-19 or whatever, our bodies would respond in a way that would damage our tissues and probably lead to our death if we didn't have some way to control that. And cortisol is produced to sort of control and tampon down that immune response to keep it from being too deleterious.
That's why people get cortisol sometimes, or dexamethasone with COVID infections. It's why people who have autoimmune conditions are treated with steroids, because it can take out that arm of the immune system and control that so it's not as dangerous and damaging.
There are just so many other things that cortisol does as a modulator of metabolism and body function. And it's there to sort of increase fuel. That's why it's called a glucocorticoid, because it's increasing glucose and modulating the stress response and helping us maintain what we call homeostasis, or our body's interaction with the environment so that we can survive the things that we encounter.

Pathak: And you mentioned earlier that when there is an excess amount of cortisol, you can see patients present with things that are obvious to the eye and some that aren't so much so. Can you clarify the constellation of symptoms that people should recognize if there is a concern about excess cortisol levels?

Blevins: So the things that we usually see in people — they'll talk about gaining weight, usually an inordinate amount of weight in a short period of time. You know, 50 pounds in a year or two is not atypical. I've seen people double their body weight in a three- or four-year period, go from 120 pounds to 240 pounds, for example.
But it's a weight distribution. It's interesting — it's more around the central parts of their body, whereas their arms and legs might become thinner because of the muscle atrophy, and fat metabolism is different in different parts of the body. So people actually lose subcutaneous fat sometimes over the hands and the feet.
General obesity — usually people have obesity throughout their body — but Cushing’s patients usually have what we call central obesity. So that's another common feature. People are often said to have a rounded face, used to be referred to as moon facies, but people look like people and not the moon, so I don't like to use the term moon face. They tend to get a reddened face. They can develop hair growth, excessive fine hair, sort of thin wispy hair, not thick terminal hairs. That's common, but not as common as you might think — it's more what we call hypertrichosis, just a lot of very thin downy hairs on the face that we can see.
The muscle strength is a problem. The easy bruising, thin purplish stretch marks — they're not always purple, sometimes they're pink, and they're not always greater than a centimeter, sometimes they're thin. But those are the things that I think are the obvious symptoms and signs.
Some of the non-obvious or hidden things are hypertension — you don't know you have hypertension until they check your blood pressure — hyperglycemia — you don't know you have that until they check your blood sugar. If you have those things, you might be on more than one drug and still not have control. Osteoporosis is another hidden feature where you don't know you have that unless they check your bone density. Cortisol does destroy bone and leads to calcium losses, can cause kidney stones, for example.
So that's a combination, I think, of the obvious and the hidden things. Another thing that just came to mind is the hyperlipidemia — you don't know you have that until your blood lipids are checked — or hypercoagulability and a higher risk of blood clots. That's not seen until you have something else that usually puts you at risk for blood clots, like surgery or an injury or a long plane ride or something like that. So that's pretty much the main combination of the things that we see with this particular disorder.

Pathak: So if someone's listening and feels like, huh, I feel like I'm exhibiting a lot of these symptoms, or someone I love is, what would be the next step in terms of diagnosis if they came to their primary care doctor and said this is something I'm concerned about?

Blevins: Well, obviously bringing it to the attention of healthcare provider is the first step. And, and then asking for — borderline insisting for — I mean, we don't, we sort of sometimes don't like it when patients insist on things that they don't need, but at least asking for a workup I think is essential.
And, you know, that might be to check an ACTH and a cortisol and a 24-hour urine cortisol. And to do an overnight one milligram dexamethasone suppression test and perhaps a couple of late-night salivary cortisols. I think those are all good screening tests. If people can get their physicians to do those things, they're halfway there insofar as getting a diagnosis made.
And what I mean by halfway is that the second half of it is to have someone who knows how to properly interpret the results, and then if there is still clinical suspicion to go forward with an investigation to try to determine who might actually have the disease. One of the things that I like to draw an analogy to is when I was in medical school and working in the general surgery rotations, the surgeons did a lot of operations for possible appendicitis, and sometimes the appendix was normal.
Sometimes they found infection, sometimes they found a little carcinoid tumor or some other process. But they would always say, if you don't do enough negative surgeries, you're not getting all the people that really have the disease. And I think the same is true of working people up for Cushing’s.
If you're not getting mostly negative workups, you're not testing for it enough. And I would suspect that in my practice, 50% of the people referred to me have it. 50% don't. For a primary care physician, it might be five to 10% would have it if they worked up, and maybe the remainders wouldn't because they need to be screening a lot more people to find the disease, which will then be enriched in my practice.
And if we're not seeing that, we're not doing enough workups. The problem for the busy primary care physician is they're gonna say, so you mean I have to work up 20 people to find one? And the answer is, yes, you do. They're used to finding negative workups and may abandon that workup because it's always negative.
But if they wanna find the one of 20 that's getting worked up that has the disease, they have to do those 20 studies. And maybe the number is one of 50 or, or three of a hundred, I don't know what the number is. I'm just estimating based on experience that not everybody who gets worked up has Cushing’s, but you're not gonna find the people with Cushing’s if you don't work up people in the first place.

Pathak: Talk to us a little bit about why a diagnosis can take time.

Blevins: Several reasons. One, because no two patients are the same. Everybody's a little bit different. You could give me a hundred people, let's say, with a pituitary tumor causing ACTH production causing the same level of 24 urine cortisol. Every patient's gonna be different. It's a hundred patients with the same disease, but a hundred different illnesses because of the way the tissues respond to the cortisol.
Some people have genetic makeups that lead to, say, metabolic syndrome, so those are the people that are more likely to get diabetes, hypertension, and obesity, where if you don't have those genes, you might be more likely to get osteoporosis and, say, hypertension or depression. And every case is different.
And I think that that's part of the problem is that people — people meaning physicians — learn in medical school that, uh, here's what Cushing’s looks like. So, the first stage is getting past this discordance between clinical features and laboratory results. So a physician may look at these results and say, well, yeah, some of these are abnormal, but you don't look like you have Cushing’s, so don't think you have it.
Well, that's not the right way to proceed with those results in that clinical scenario. So that's the first thing that leads to delays and takes time, is the physician has to sort of get on board with what they see physically and biochemically to proceed to the next step. The next series of tests usually would be confirmatory tests to prove whether it's really hypercortisolism, and sometimes that takes a few weeks to straighten that out and get an answer or get the test done properly if anything's borderline to repeat the studies.
And then after that you get studies that may include an MRI of the pituitary if it's ACTH-dependent, and if that's positive, great. If it's negative, you might need to do other studies to look for ectopic ACTH production, or if the biochemistry suggests adrenal, you need to get a CT. So most of the time, if I order an MRI at my facility, it's a six-week wait.
You know, CTs can be four weeks, sometimes you get 'em quicker, but usually there's a waiting list. So before you know it, you're three or four months into working up a patient and trying to arrive at a conclusion about a disease, yes or no, so that you can define treatment and get patients to the next step.
So that's the system we live in. I often have patients say, well, can't you just admit me to the hospital? And I'd love to do that, but insurance isn't gonna cover that. So much of what we can do is defined by what insurance companies are willing to compensate the healthcare system for.
And they wouldn't allow those admissions. I remember early in my training we had a few people that we could admit for a workup, but by and large, most of the time we were doing the studies as an outpatient. The biggest problem there was a lot of the research that sort of was done in the 1980s and nineties to define different cutoffs for tests and the best ways to work patients up were done at the NIH and patients had been in the hospital for months and months, and you can't really translate the results of those studies to the outpatient practice where there might be some difficulties in getting a 24-hour urine.
And the fact that people are working from their home to get testing is different than working from a hospital bed in a facility that's designed to do clinical research. So we have to sort through all of those things and it's not as — Cushing’s is not as easy as you might think. I mean, I certainly see easy patients, but it's not easy.
It's easier to tell a patient that they don't have it and to be confident about that than sometimes it is to address those that sit on the fence where I can't decide whether you have it or not. I think you do, but I'm not sure — your scans are negative — and we put those patients into a further delay where, as one of my colleagues used to say, the patient needs a tincture of time, so you need to repeat studies in six months because she usually gets worse over the period of six months to 12 months or so.
So you sometimes have to follow people to zero in on whether they have the disease or not.

Pathak: You've mentioned pituitary causes, adrenal glands. Can you tell us a little bit more about common causes of Cushing’s syndrome?

Blevins: Sure, that's something that's evolving as we understand adrenal diseases more. It used to be said that probably two thirds of patients with Cushing’s syndrome had Cushing’s disease due to a pituitary tumor. About 80% of those are small tumors and 20% are bigger tumors. A small number of people might have what we call pituitary hyperplasia.
And then probably about 10% of people had ectopic ACTH production, which was a neuroendocrine tumor that was derived from some neuroendocrine cell in the lungs, the bronchus, the thymus gland, the adrenal glands, or somewhere else in a neuroendocrine tissue in the body that was producing ACTH in a dysregulated fashion.
And then the remainders, about 25% of people had adrenal disease that either had a benign tumor called an adenoma or adrenal hyperplasia or adrenal cancer. What we now know is that probably if you test everybody with adrenal disease, more of them have what we call autonomous cortisol secretion or mild autonomous cortisol secretion. Some have frank elevations in cortisol, but we're seeing that adrenal disease is emerging as probably as equal to pituitary disease in causing this disorder.

Pathak: That's really helpful, and I'd love if you could also help us understand a little bit around pseudo-Cushing’s — so where you may have physiologic hypercortisolism, so high levels of cortisol, but that the axis is not abnormal because of these tumors.

Blevins: This is another interesting arena where my thoughts are evolving and I believe the thoughts of colleagues are evolving as well. Pseudo-Cushing’s is the classic term that's always been used to say it's a false form of Cushing’s. I mean, they do have Cushing’s because many of them look very Cushing’soid. They look just like Harvey Cushing’s index patient. But others don't look Cushing’s at all, just like some of my other patients with hypercortisolism.
I think people have mostly now started to try to move to the term that's called non-tumor hypercortisolism, but that could also include people on medications. I don't think that's exactly the most accurate term. Others are saying non-pathologic hypercortisolism, trying to imply that it's not due to pathology but is due to dysregulated physiology. That's a reasonable term because it's usually seen in people that have a history of alcoholism with alcohol withdrawal and DTs on multiple occasions or those who are hospitalized or in alcohol treatment programs.
People with severe melancholic depression, including several of my own patients, can develop this condition. We've had people that work in the financial environment of San Francisco who have hypercortisolism and they turn out to be normal, and it's just related to the stress of their work. Uncontrolled severe, poorly controlled, I should say, diabetes mellitus has been associated with it.
Some of those people actually really do have Cushing’s. In any of these groups where we think a patient might have pseudo-Cushing’s, they could actually have Cushing’s. I'm remembering a patient that I saw years ago who was followed by the endocrine department of my institution and was actually told for years that she had pseudo-Cushing’s and ultimately made her way to me, and she clearly had a pituitary tumor and real Cushing’s. I've seen that repeated over and over from doctors in the community who tell patients they have pseudo-Cushing’s. So they come see me and they find out it's the real disease.
And then I've seen people who were told they had the real disease and it's really non-pathologic cortisol secretion due to uncontrolled diabetes or depression or something like that. So I've come to the conclusion that anytime a doctor thinks a patient has pseudo-Cushing’s — even this applies to me too — they probably ought to see another equally qualified pituitary endocrinologist for an evaluation to get another opinion, just so that there's two physicians who are qualified determining whether this patient has a disease or a physiologic process that activates cortisol secretion, so that the diagnosis is correct in the long run.

Pathak: Strikes me as you were speaking that this is really an area where collaborative care is so important. And by that, I mean really the voice of the patient themselves and what they're experiencing, the primary care doctor, specialists, potentially even multiple specialists, to really hone in on the most accurate diagnosis.

Blevins: You're absolutely right. That is essential. We encourage patients to continue to work with their primary care physicians because I don't manage diabetes and hypertension and depression and things like that, so that's essential. The collaboration also, when it comes to looking at MRIs and CT scans, to involve either neurosurgeons that do pituitary operations or endocrine surgeons that do adrenal operations is also an important part of the evaluation because everybody has a little more expertise than someone else when it comes to reading films and the judgment and compiling all the data and arriving at a diagnosis. And then, you know, we're 40 miles up the road from Stanford. I send patients to them. They send patients to me for evaluations periodically, just to have another set of eyes on the patient's situation, especially if it's not clear or if we've disagreed with a referring physician or even disagreed with the patient's own sense about what's going on.

Sometimes patients come with very strong opinions about whether they have a disease or not, sometimes based on Google searches or interactions with others on social media, and if there's ever a disagreement, a second opinion is the best thing to do. I mean, I don't think that any of the people that I work with have egos that don't allow them to send patients for second opinions. Certainly some have egos that would be harmed by that, and they would never send a patient for another opinion. But I think in this day and age, that's less of a problem than it used to be. And patients with Cushing’s are some of the most difficult cases to diagnose because of the subtleties and vagaries of the disease in the presentation. So I think a team approach is essential in this arena.

Blevins:

Pathak: I'd love to sort of, as we get to the end of our time together, we spent a lot of time on what Cushing’s syndrome can look like, why diagnosis can be a journey. Can you give us some information about what the treatment journey looks like?

Blevins: Well, the treatment journey depends on the underlying condition. It usually starts with, if you have pituitary disease, a surgical procedure to try to resect your tumor. If that can be done successfully, then it's long-term follow-up to assess for recovery of pituitary adrenal function and also whether or not there's a recurrence.

If you have adrenal disease, that's a more straightforward, more likely to be successful procedure, depending on whether one or both adrenals need to be removed. There's different follow-up and treatments afterwards. And if you have ectopic ACTH or it doesn't appear it's pituitary-oriented ACTH secretion, the biggest part of the journey upfront is to find the tumor and then try to prescribe surgery to remove it, and if it can't be removed, to treat with medications. Those people with pituitary disease who can't be cured, who have recurrences are also usually treated with medications, sometimes surgery.

You know, but the treatment is very specific to the underlying condition, and it can be one step or multi-step, but most patients do require lifetime follow-up to assess for recurrent disease, and if they have had their adrenals removed, to sort of manage their adrenal insufficiency.

Pathak: That's really helpful. I'd love to cede the floor to you in our last few moments together to really talk to our listener who maybe thinks that this is a discussion they wanna have with their provider. What are the most practical next steps on their checklist? What would you encourage listeners to do?

Blevins: I would encourage listeners to devise and write down briefly—don't take five or 10 pages. Maybe keep things to one-page doc. If you keep things to one page, most of the time physicians are willing to read that with you or in front of you. But write down your symptoms and write down that you learned about this condition and that you want to be tested and suggest a few tests and see if they will work with you to do those things.

Unfortunately, a lot of physicians are busy and dismissive and they've never seen a case, so they may not be interested. But I think this era of physicians are more interested than in the past, but you still might have some resistance. In that case, see an endocrinologist. I think endocrinologists are used to doing these investigations to see whether someone has Cushing’s disease or syndrome, and if the tests are positive, work with your doctor to try to find out why, and then if that physician's not comfortable treating, to gain a referral to an academic medical center that has expertise in either pituitary and/or adrenal disorders that cause hypercortisolism.

Pathak: That's really, really helpful, and I wanna thank you so much for your time.

Blevins: You're very welcome. It was nice to join you.

Pathak: I'd like to share three key takeaways from my conversation with Dr Blevins. First, Cushing’s syndrome isn't just elevated cortisol from high stress. Cushing’s syndrome is a complex and often under-recognized condition. Delays in diagnosis are common, not because patients are wrong, but because presentations vary and testing can require persistence.

Red flags can include weight gain around your belly and thinner arms and legs, muscle weakness, easy bruising, stretch marks, and facial changes, plus silent complications like high blood pressure, diabetes, osteoporosis, high cholesterol, and sometimes even increased blood clot risk. The clinical clue is pattern and pace, meaning multiple changes that seem to come together.

Second, diagnosis is a process that requires appropriate testing and careful interpretation. Cushing’s can look different from person to person, and classic physical signs aren't always present. Dr Blevins highlights the need for appropriate tests, often including an endocrinologist with pituitary and adrenal expertise. The workup can be slow because results can be borderline. Symptoms can vary widely, and imaging and follow-up tests take time, but persistence is essential.

Finally, Dr Blevins emphasized that informed self-advocacy matters. Patients who document their symptoms, ask for appropriate testing, seek second opinions when needed, and work collaboratively with both primary care physicians and specialists are more likely to reach an accurate diagnosis. Shared decision-making grounded in patient education, transparency, and trust is essential for navigating both the uncertainty and the length of the diagnostic journey.

For listeners, the practical move is to bring a one-page symptom summary, request appropriate tests, and if results or suspicion persist, seek endocrinologists and sometimes a second opinion at a pituitary or adrenal center.

If this conversation brought up feelings of frustration or doubt because you felt dismissed or unheard in the past, know this: Needing answers, asking questions, or seeking another opinion is not a failure. It's an important part of caring for your health. To find out more information about Dr Lewis Blevins and Cushing’s syndrome, make sure to check out our show notes.

Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you are interested in or questions for future guests, please send me a note at [email protected]. This is Dr Neha Pathak for the WebMD Health Discovered Podcast.