Spit Happens: The Truth About Cortisol Testing

Picture three women. One is spitting into four little tubes throughout the day, mailing them off to a lab, hoping to finally get answers about her "adrenal fatigue." Another has been on a steroid inhaler for years, or just got a cortisone shot in her knee, and has never once had her adrenal glands checked — even though statistically, she has roughly a coin-flip's odds of an abnormal result if anyone bothered to look. And a third, in her late forties, is being told her exhaustion and brain fog are adrenal fatigue, when what she actually needs is a conversation about perimenopause.

Same hormone. Same small gland sitting on top of each kidney. Three completely different ways we get this wrong — and in this episode, Dr. Patil-Sisodia untangles all three.

She starts with the myth: why multi-sample "adrenal fatigue" saliva and urine kits run on real, legitimate lab technology in service of a diagnosis that doesn't medically exist — and why that combination is exactly what makes them so convincing. Then comes the plot twist she didn't expect to be making: that same multi-sample saliva format is actually a gold-standard tool, just for something else entirely — screening for Cushing's syndrome, when cortisol runs too high instead of too low. From there, she walks through the tests that genuinely work for Cushing's, the pseudo-Cushing's patterns (depression, alcohol use, obesity, PCOS/PMOS, illness, and more) that can mimic it on paper, and the condition she says gets missed more than any other: steroid-related adrenal insufficiency, which affects about half of long-term steroid users — inhalers, creams, sprays, and injections included — while fewer than 1% are ever tested for it.

The episode closes on something close to home for this show's listeners: how easily perimenopause gets relabeled as adrenal fatigue, what that mislabeling actually costs women, and three simple questions you can run any cortisol test through before you trust it.

Time Stamps:

[00:00]  Medicine Gets Cortisol Wrong — the three-part setup: wrong tests, wrong people, and the people who need testing but never get it.

[01:07]  Adrenal Fatigue Myth — why multi-sample saliva/urine kits use real lab technology to chase a diagnosis with no recognized normal range.

[03:08]  Real Use for Saliva — the plot twist: late-night saliva testing is legitimate gold-standard science, just for a different question.

[06:19]  Cushing Syndrome Basics — the three tests that actually work: late-night saliva, 24-hour urine cortisol, and overnight dexamethasone suppression.

[07:34]  Pseudo Cushing Pitfalls — how depression, heavy alcohol use, obesity, poorly controlled diabetes, PCOS/PMOS, illness, pain, eating disorders, and intense exercise can mimic Cushing's without being it.

[09:19]  Steroid Induced Adrenal Suppression — the condition affecting roughly half of long-term steroid users (inhalers, creams, sprays, injections, possibly Depo-Provera) while under 1% get tested.

[12:57]  Menopause Misdiagnosed — why perimenopause symptoms get scooped up under the adrenal fatigue umbrella, and what the research does and doesn't show.

[17:06]  Testing Adrenal Insufficiency — the real diagnostic pathway: tapering first, the 8–9 a.m. blood draw, and how to read the result range.

[18:55]  Cosyntropin Test Myths — the standard 250-microgram test versus the unvalidated low-dose version some sources still promote.

[21:06]  Recovery and Reassurance — why an abnormal cortisol number is far more common than a true adrenal crisis, and why recovery can take months to over a year.

[22:21]  Three Questions for Testing — what to ask before trusting any cortisol test: proven diagnosis, meaningful timing, gold-standard validation.

[24:19]  Final Takeaways and Outro.

Key Takeaways

• "Adrenal fatigue" and "chronic stress" are not recognized medical diagnoses — there is no validated normal range for the multi-sample panels marketed to diagnose them.
• The same multi-sample saliva testing format is legitimate gold-standard science — when it's used correctly, at the right time of night, repeated 2–3 nights, to screen for Cushing's syndrome.
• About half of people on long-term steroids (any form — pills, inhalers, creams, sprays, injections) have some degree of adrenal insufficiency. Fewer than 1% are ever tested.
• Perimenopause symptoms (fatigue, brain fog, anxiety, low libido) overlap heavily with the symptoms marketed as "adrenal fatigue" — and that overlap can delay real menopause care.
• Before trusting a cortisol test: ask what it's proven to diagnose, whether the timing matches the question, and whether it's been validated against the gold standard.

Resources & Links

• Follow Dr. Patil-Sisodia: @drpatilsisodia on Instagram and TikTok
• Send fan mail / episode questions via Buzzsprout
• Catch up on the related myth-busting episode referenced in this one (adrenal fatigue supplements)

Thanks for listening. Find more info about Clearly Hormonal on the website or Instagram.

Transcript

0:01

Welcome to Clearly Hormonal, the podcast where we stop googling our symptoms at midnight and actually start understanding what's going on in our bodies. I'm Dr. Komal Patil-Sisodia, an endocrinologist, internist, obesity medicine specialist, and a Menopause Society certified practitioner, which is really just a whole lot of words to say hormones are kind of my jam. I've spent 17 years watching women try to navigate their hormonal health without ever having been taught the language for what's happening in their own bodies, and then meeting clinicians who want nothing more than to help them figure it out, but are up against 10-minute appointments and a system that just wasn't built for it. This podcast is my answer to that gap. We'll cover menopause, metabolism, hormones, and everything in between with real evidence, not trends, and without the overwhelm. A quick disclaimer. I'm a physician, but this is education, not personalized medical advice. Take what resonates and discuss it with your own healthcare team. Now, let's get into it and talk about what's clearly hormonal and what's not.

Dr. Komal Patil-Sisodia 1:04

Here's one of the things that I find a bit funny and frustrating about medicine in general and about today's topic. We're testing the wrong people with the wrong tests, and at the same time, we're not testing the right people at all. So picture this, somewhere right now, someone is spitting into four little tubes throughout the day, mailing them off to a lab, hoping to finally get answers about their, quote, "adrenal fatigue," which is not a real diagnosis. And meanwhile, someone else who's been on a steroid inhaler for years or just got a cortisone shot in their knee or their back has never once had their adrenal glands checked, even though statistically about half of the people in exactly the same situation would test abnormal if anyone bothered to look. And somewhere else, a woman in her late forties is being told that her exhaustion, her brain fog, her anxiety are adrenal fatigue, when really what she needs is a conversation about perimenopause. Same hormone, same little gland sitting on top of your kidneys, and three completely different ways we get this wrong. So let's untangle it together. First, I wanna talk about the myth of adrenal fatigue and the cortisol curve. And let's talk about this directly. The Dutch test and those multi-sample saliva or urine kits that promise to map out your cortisol rhythm throughout the day, they're marketed for adrenal fatigue, which again, we talked about in the last episode and is not an actual medical diagnosis in chronic stress. And here's what's tricky. These tests are expensive, they make claims about something that doesn't exist, but they use real legitimate lab technology, the same precise machinery that hospitals use for actual hormone testing. The equipment is trustworthy, and that's exactly why it's so convincing. It's a good machine, but the wrong question. And here's the main problem. There's no agreed upon normal range for these panels when it comes to diagnosing a real adrenal problem like adrenal insufficiency or Cushing syndrome. There's none. And that's not a small gap in the research. It's something the major medical guidelines will say outright. Adrenal fatigue and chronic stress aren't recognized medical diagnoses that have cortisol testing behind them. There's no test for them because medically speaking, they're not a defined condition. Your cortisol is naturally low in the afternoon and the evening, and that's completely normal. So measuring it at multiple points all day and reading meaning into the shape of that curve isn't how doctors actually evaluate your adrenal glands And here's one thing I want you to take away from that. This was never really about spit testing versus blood or one sample versus four. It's about whether a specific test taken at a specific time has actually been proven to answer a specific medical question. So let's keep that in mind because it's going to matter a lot in the next segment, because this is where the answer gets more interesting. Next, I want to talk about the plot twist, which is that multi-sample spit testing is real, but it's just for a different question than what these other tests are claiming to answer So here's the plot twist. Multi-sample spit testing is actually real, but it's just for a different question. Adrenal fatigue and chronic stress are not going to be answered by this multiple sample spit testing. Here's where I think it gets interesting and where I want to correct myself slightly from an earlier episode. Testing your saliva multiple times isn't automatically fake science. In fact, collecting a late night saliva sample two or three nights in a row is one of the gold standard tests we use for screening for Cushing's syndrome, which is where your body makes too much cortisol. This test catches the right diagnosis about ninety-six percent of the time and correctly clears people who don't have it about ninety-three percent of the time. And that's genuinely strong performance for a screening test. Here's the key difference. This isn't a curve across a whole day. It's the exact same time that these samples are checked for Cushing's syndrome, usually for people who have a normal sleep/wake cycle around eleven PM. And we repeat it two or three nights in a row because cortisol can bounce around a lot from one night to the next, and one sample alone might mislead you. And for people who are night shift workers, eleven PM doesn't even work, right? We want to time this right before they're going to bed because generally cortisol is the lowest before you go to bed. And so if you're a night shift worker and you're getting home at seven AM or eight AM and you're going to bed around nine or ten AM, we will do this testing an hour before you go to bed instead of eleven PM because at that point you're up working and the test wouldn't have the same value. So when you check it and the method by which you check it actually really matters based on the question that you're trying to answer. And this is what we do for Cushing's syndrome. So let's compare the two. The adrenal fatigue kits will take one sample at several different times of day, and there's no proven benchmark to compare it to. The Cushing's test will take several samples at the exact same meaningful time of night or day if you're a night worker, and it's backed by real research, so we're actually answering a real medical question. And here's what I want you to take away. Taking several samples doesn't automatically make a test invalid, and taking one sample at several different times of day doesn't automatically make it valid either. What matters is the timing of the test and the question being asked, not how many tubes you spit into. And sometimes people are misled to believe that the more testing they do throughout a day is going to get them a better answer, and that's not necessarily the case. So let's talk about the other side of the coin, when cortisol is running too high. We have talked a lot about, in the last episode and in this episode, what we do when cortisol is too low. Let's flip it around. Cushing syndrome is what happens when your body makes too much cortisol, and it gets missed or misread surprisingly often too, but just in the opposite direction. And here's three tests that actually work for testing Cushing syndrome. The first is gonna be the late night saliva sample that we talked about, eleven PM repeated two to three nights in a row. Or if you're a night shift worker, whatever time is an hour before you go to bed, two or three days in a row. Second is a twenty-four-hour urine collection that measures your total cortisol production that comes out in your urine for that twenty-four-hour period. And third is a simple overnight pill test where you take a small dose of a steroid called dexamethasone, and you see how your body responds. Any one of these or a combination is the right place to start if your doctor suspects Cushing syndrome The tricky overlap can be when stress looks like Cushing syndrome but isn't. Here's the catch. All three of these tests can come back looking abnormal even when somebody doesn't have Cushing syndrome, and doctors will call this pseudo-Cushing. Basically, your body is making more cortisol because of real stress on the system, not because of a tumor or a true hormone disorder. And the list of things that can cause this is going to sound familiar to a lot of you listening. First on the list, depression. Up to eighty percent of people with major depression have some disruption to their cortisol patterns. Number two, heavy alcohol use. Number three, obesity and poorly controlled diabetes. Number four, PCOS, now known as PMOS or polyendocrine metabolic ovarian syndrome. Physical stress on the body like being hospitalized, recovering from surgery, being in pain, and then eating disorders and very intense exercise. In true pseudo-Cushings, the numbers will only be mildly elevated, while real Cushing syndrome shows much bigger elevations. But there can be a genuine overlap in the middle, which is why doctors have a couple more specialized tests in their back pocket for truly confusing scenarios. So here's what I want to do to reassure you, is that if you have a late night salivary test done and it's normal, or a normal dexamethasone suppression test, which is that normal overnight pill test, that's generally reassuring news. In plain terms, if any test comes back normal, it is very, very unlikely that you have Cushing syndrome, even if you happen to be dealing with stress, depression, or another condition that can kinda nudge your cortisol up a bit. Next, let's talk about the condition that everyone's missing, and this is steroid-related adrenal insufficiency. And I want you to remember this part the most because what happens is much more common than we think, and the numbers for how frequent this can be are a bit shocking. The stat is that about half of people on long-term steroid medication or ones who stopped one recently have some degree of adrenal insufficiency, meaning their adrenal glands aren't making enough cortisol on their own anymore. But less than one percent of people in that situation have actually ever been tested for it. Half. That means almost nobody gets checked. And this isn't just about people taking prednisone pills for a chronic illness. Any form of steroid can quietly shut down your adrenal gland's own natural production, including steroid pills, steroid inhalers, yes, these are the ones that people take for asthma or COPD, steroid creams if people are using them long-term and have to apply them to large parts of their body, steroid nasal sprays that we so commonly use for allergies. I know I buy a multi-pack every time allergy season rolls around. And then steroid injections, which is the cortisone shot that you get in your knee or your shoulder. All of those can affect how your adrenal glands function and make them a little lazy. It kind of like puts them to sleep. Here's another one that I find really, really interesting, and I had only ever read about this in textbooks until I actually saw a case of this. So a common form of birth control is Depo-Provera, which are injections that you get every ninety days to suppress your ovulation and help with contraception Depo-Provera can suppress your adrenal axis, and I've had one person develop adrenal insufficiency after getting Depo-Provera shots every three months for two decades. And they presented to the emergency room with adrenal insufficiency. We couldn't exactly figure out what it was. And because Depo doesn't always make it onto the med list, it was one of those things that I didn't even know that the patient was getting until we talked about it two years into her diagnosis, and then the light bulb went off in my brain, and I just thought, "Oh my God, I totally missed this." But now we are in a position where we are figuring out a solution to help get this person off of their Depo injections and hopefully be able to taper them off their steroids. So there can be several different things that we hand out pretty commonly that can cause this adrenal suppression. So who should actually get checked? Doctors recommend paying closer attention if any of this sounds like you. If you're tapering off a steroid that you were recently given or recently stopped one after being on a high dose for a long period of time, if you're using more than one type of steroid at a time, so cream plus a spray or cream plus pills, if you're using a steroid inhaler or a cream at a high dose or for more than a year, if you've had a steroid injection within the last two months, and then if you're taking certain antifungal or antiviral medications that can make steroids stick around in your system more. If any of that sounds like you or someone you love, it's worth a real conversation with your doctor and not just a panel you order online And lastly, I want to talk about what happens when menopause gets mislabeled as adrenal fatigue, and I see this so commonly. This is another way this whole conversation gets derailed, and it matters to a lot of women who are listening to this show specifically. Adrenal fatigue isn't just an unproven test, it's not a real diagnosis. I can't say that enough. The major endocrine medical associations have said this outright. It's a label that isn't recognized by the doctors who specialize in hormones, and there's a real downside to it that's worth sitting with. Adrenal support supplements, and I talked about this in the last episode, will sometimes contain undisclosed thyroid or steroid hormones, and treating someone for their adrenal fatigue can actually end up hiding a real diagnosis under it, including menopause. And here's why the mix-up happens. It comes down to symptoms simply overlapping. Brain fog, fatigue, anxiety, difficulty sleeping, mood changes, lower sex drive. These are all very common menopause symptoms, but they're also incredibly non-specific. A huge study that looked at over one hundred and forty-five thousand symptom reports found that fatigue, headaches, anxiety, and brain fog show up at every stage of a woman's reproductive life, not just menopause. In one large study, the only symptoms that reliably pointed specifically to the menopause transition were hot flashes and vaginal dryness. Everything else, the low energy, the anxiety, the body aches, the memory issues, show up plenty before and after the transition and can be related to entirely different medical conditions And here's the problem, those exact same vague symptoms are the ones that get scooped up under the adrenal fatigue umbrella by people who are pushing that as a diagnosis. So a woman in perimenopause describing fatigue and brain fog may walk away with an adrenal fatigue label instead of actually having a conversation about hormone therapy that could help her. But here's the thing, nobody has actually studied how often menopause gets mistaken for adrenal fatigue. That specific number doesn't exist in the research. I actually tried to look it up. What we do know for certain is why it happens, which are the overlapping vague symptoms plus a made-up label with no real diagnostic test behind it. So let's keep things straight. Real adrenal insufficiency, where your adrenal glands genuinely aren't working, is actually quite rare. We are talking a tiny fraction of a percent of people, and it tends to come with its own distinct clues. Skin darkening in places like the creases of your palms or the mucosa inside of your cheeks, feeling dizzy when you stand up, craving salty foods, losing weight without trying. And abnormal sodium levels on blood work. That is a pretty different picture from a woman in her late forties dealing with fatigue and brain fog. And the stakes here are real. Menopause symptoms are already wildly under-treated as it is. Adding an unproven detour through adrenal fatigue before someone gets into real evidence-based conversation about menopause is not a harmless delay. It's time that that woman could have actually spent feeling better So let's talk about how to actually get a diagnosis of adrenal insufficiency the right way. First and foremost, if you are on a steroid, you need to taper down to a low steady dose before we can actually accurately test you And when I'm talking low dose, I'm talking something close to what your body would naturally make on its own. Testing too early when you're on a high dose gives you an inaccurate picture. Second, a morning blood draw between eight and nine AM, at least a full day after your last steroid dose. And here's something really important. Doctors will think about the results as kind of a scale, not a strict cutoff of either you're fine or you're not fine. A higher cortisol number, usually over 10, suggests that your adrenal glands have recovered and the steroids can be stopped safely. A number between five to 10 is genuinely unclear. And a number between five to 10 is unclear. And generally what I will tell my patients to do is stay on your lower dose of steroid and we'll retest again in a few weeks or months. And then if there is a low number, like less than five, it makes me worry about true adrenal insufficiency. If it's less than three, that's almost diagnostic in my mind, and we need to do some additional testing The third thing to know is that doctors will specifically recommend against jumping straight into more involved testing for everyone who's tapering off of steroids. It's really saved for situations where the morning blood test comes back unclear or there's still real concern. And there's a quick myth to bust here too. And here's another quick myth to bust. When I am worried about adrenal insufficiency, I will do what's called a cosyntropin stimulation test. There is a lower dose version of that stimulation test that gets talked about again and again, but it's not actually recommended, and it doesn't work better than the standard version. It isn't even something labs can reliably get their hands on. So again, you wanna make sure that you are actually getting a medically validated test instead of something somebody made up to try and prove a diagnosis that may or may not exist. And here's something that I want to reassure everybody with. Having an abnormal cortisol number is actually a lot more common than having a dangerous true adrenal crisis. Even in the people who test abnormal, the risk of a real emergency is not super high. And one quick myth to bust here, too. There's actually a low dose version of the cosyntropin stimulation test that we use when somebody's fasting morning cortisol numbers are a mid-range or are actually low. Usually we will give 250 micrograms of cosyntropin as an injection and then measure how the cortisol rises in somebody's bloodstream. If it pops up over 18, I think the newer lab assays have it cut off over 15, you don't have adrenal insufficiency. But there's an older test that people talk about called the one microgram cosyntropin stimulation test. And interestingly, it has not been shown to be as accurate as the 250 microgram cosyntropin test, and it's not recommended by the different endocrine societies. It's important to note that you need to have the right tests done, and sometimes people are not always doing that. So be aware of what you're being asked to have performed. Most medical centers have the 250 microgram cosyntropin stimulation test. I know that's getting into the weeds a little bit, but I just want you to know that that other one is out there and people are touting it as just as good, but it's not. And I want you all to understand something, which is that having an abnormal cortisol number is actually a lot more common than having a true dangerous adrenal crisis, especially if you've been on steroids for a while. The odds of you going into an emergency is pretty low, and testing exists to help your doctor know whether it's safe for you to come off of those steroids, and it's not a hurdle you have to clear before you're allowed to keep tapering. Depending on how long you've been on steroids, your body may need additional time to recover, and this can take anywhere from a few months to over a year. I have people who've been on steroids for years, and it's taken me years to taper them off of it. This is not a process you want to go through quickly because you'll feel pretty terrible. It's pretty normal for it to take a long time because the adrenal glands can take a bit to wake up once they haven't had to work quite as hard Recovery can take anywhere from a few months to over a year for your adrenal glands to wake up after being on steroids for a long period of time. That's completely normal, not a sign that something's gone wrong. Let's pull this episode together into something you can actually use, whether you're a patient that's being offered a test or you're just trying to make sense of an ad you saw online, or you're just trying to make sense of an ad you saw online. Here are three questions that I think it's important for you to ask any time you're considering cortisol testing. Number one, what specific condition is the test actually proven to find? Not stress, not adrenal fatigue in general, but a real named medical diagnosis like adrenal insufficiency or Cushing syndrome. Number two, is the timing meaningful for your body? For example, for adrenal insufficiency, because cortisol levels are highest in the morning, you want that morning testing. If your cortisol is low first thing in the morning and you have a normal sleep-wake cycle, you may have adrenal insufficiency. On the flip side, if you have Cushing syndrome, where your adrenal glands are making too much cortisol, the late-night testing on several different nights is gonna be very useful to help you figure out whether you have Cushing syndrome. If you are being offered tests that you do throughout the day, to me, that's a warning sign and not a selling point. That test is probably not diagnosing a true medical diagnosis. And then number three, has this exact test been compared against the gold standard way doctors actually diagnose this medical condition, right? So if you're trying to diagnose adrenal insufficiency or Cushing syndrome, are you being offered a gold standard test or are you being offered something alternative that hasn't been proven? Good lab equipment doesn't automatically mean that it's being used in the right way, so you really need to be aware of what you're being offered in terms of testing. If you run any cortisol test you're offered through these three questions, you'll almost always be able to tell whether you're looking at real proven medicine or a wellness product that's just borrowing the language of science. Here's what I want you to take away from today's episode, and I really want this to stick. This was never about saliva being a bad test or blood tests being good, or one sample being better than four or vice versa. Good testing simply means matching the right sample, the right timing, and the right method to the real medical-- to a real medical question. That kind of precision in data protects people in more ways than one. It keeps us from over-testing and over-diagnosing with kits that were never actually proven to work. It saves you money. It makes sure people who really do have steroid-related adrenal problems or Cushing syndrome or adrenal insufficiency don't slip through the cracks, and it stops a made-up label like adrenal fatigue from standing in the way of women getting real honest answers about perimenopause and menopause. If this episode changed how you think about a test you've already had or one you've been wondering about, I'd love to hear about it. Please feel free to reach out to me with questions either through fan mail on Buzzsprout or find me on my socials @drpatilsisodia on both Instagram and TikTok. Thanks so much for listening to Clearly Hormonal, and I'll see you all on the next episode.