00:00:00:07 - 00:00:26:18 

Noah Reed 

Welcome back to the DUTCH podcast, where integrative medicine providers can expand their understanding of functional endocrinology and testing. And everyone, no matter who you are, can learn more about their body’s most complex communication system. I'm Noah Reed, vice president of sales and marketing for the DUTCH Test. In coming up on this week's episode. We're back to our Endocrine Essentials series with the case studies and patterns you'll find when testing with DUTCH. 

 

00:00:27:03 - 00:00:43:14 

Noah Reed 

The goal is to have a better understanding of the different sometimes confusing things you find when testing cortisol. These are questions we get asked every day during clinical consults, and Dr. Kelly Ruef will be making the complex easier for us to understand. Now on to the show. 

 

00:00:43:22 - 00:00:46:14 

Mark Newman 

Thanks, Noah, and thanks, Kelly, for joining us again. 

 

00:00:46:19 - 00:00:48:08 

Kelly Ruef 

Yeah, of course. Thanks for having me back. 

 

00:00:48:15 - 00:01:15:06 

Mark Newman 

Happy to have you. We talked about some complex patterns last time on the androgens, testosterone and DHEA. And what do we do with with all of those patterns we see in our female patients this time? We're going to talk about different type of hormone patterns, and that is related to cortisol. So, one of the things that we do that's that's unique that we sort of pioneered is people have looked at cortisol patterns as far as free cortisol for a long time up and down throughout the day or not. 

 

00:01:15:06 - 00:01:37:21 

Mark Newman 

What does that mean? And then we brought into the story the metabolites. Right. So, looking at free cortisol, adding free cortisone, which is unique. And then these cortisol and cortisone metabolites which is nice because we like to be comprehensive, but then it creates a whole like new list of patterns and things that we need to interpret for our provider. 

 

00:01:37:21 - 00:01:39:20 

Mark Newman 

So, we want to go through some of those with you today. 

 

00:01:40:06 - 00:01:41:02 

Kelly Ruef 

Yes, let's do it. 

 

00:01:41:03 - 00:02:01:17 

Mark Newman 

So, let's start with the easy ones. So why do we care about the metabolites right? Sometimes the metabolites add to the story in a way that's changing what you think of in terms of what's going on with the patient. Sometimes they're confirming what you think Let's start with a person who has high cortisol. So, we look at three cortisol, ty. 

 

00:02:01:20 - 00:02:23:00 

Mark Newman 

We know that's going to be an issue in terms of maybe anxiety or depression or they're stressed or whatever. So, if the free cortisol is elevated and you as a clinician then in our tests are also looking at what we call metabolize cortisol, which is a big concentration like lots of. And when you look at our reports, they're in the hundreds and thousands instead of single and double digits. 

 

00:02:23:03 - 00:02:31:12 

Mark Newman 

What does it mean to you when the free cortisol is elevated, and the metabolites are also elevated? What does that what does that add to the story for you? 

 

00:02:32:00 - 00:02:58:15 

Kelly Ruef 

Yeah, so that just confirms that you've got high cortisol, your adrenals are working overtime. So, the metabolites that they really do add to the picture because when the body's done with cortisol and cortisone, it metabolizes it. And the metabolites, as you said, tend to be very plentiful or tends to be like in the thousands. If you look at the number, metabolize cortisol, it's usually like the 3500. 

 

00:02:58:17 - 00:03:17:18 

Kelly Ruef 

So, there's a lot of metabolites and it can give you an idea of overall production of cortisol from the adrenal gland. So, when you've got high cortisol in the saliva or in the urine in the free form, right. And you have high metabolize cortisol, then, you know, OK, yeah, they're making a lot of cortisol OK. 

 

00:03:17:18 - 00:03:36:11 

Mark Newman 

So, when one is elevated and the metabolites are also elevated, it's confirmatory. So, anything new or interesting when we're on the low side, meaning my three quarters also low. So now I think I don't think you make very much cortisol and then the metabolites are also low. Is that the same story there, that it's just helping you be more confident in that conclusion? 

 

00:03:36:18 - 00:03:44:02 

Kelly Ruef 

Yeah, it's just confirming, OK, we got low adrenal output. Maybe this is some sort of chronic picture, chronic stress, chronic inflammation. 

 

00:03:44:09 - 00:04:13:05 

Mark Newman 

And while you're on that, let me let me ask you how do you differentiate between you don't make very much cortisol as a story, which means, hey, you're tired or whatever relative to someone who actually has suppressed cortisol. And I guess I'm thinking of like like true Addison's disease, like what is Addison's disease look like on the low end relative to someone who's just sort of struggling to make adequate cortisol to where they feel good. 

 

00:04:13:19 - 00:04:27:20 

Kelly Ruef 

Yeah. So, Addison's disease you don't see a diurnal pattern. It tends to be just a flatline of free cortisol and free cortisone. And with the metabolize cortisol, it's very, very low, OK? A lot of times it's below 500. 

 

00:04:28:00 - 00:04:57:20 

Mark Newman 

OK, yeah. In my mind I've always had like a thousand because we sort of tend to obsess with round numbers. Yeah. But if you're below a thousand, you know, I'm wondering, and then if you see the free cortisol basically like close to zero, then that's a pretty good confirmation that and we tend to think of Addison's, but do you tend to see patients coming through that look like that more that have Addison's disease actually, or where they're taking some sort of medication that's just suppressing and knocking down their cortisol production? 

 

00:04:58:00 - 00:05:20:06 

Kelly Ruef 

Yeah. So, most of the time they don't have Addison's. Most of the time they're taking prednisone, or they got a hydrocortisone shot. So, we know these glucocorticoids can really suppress adrenal output. And so, a lot of times, yeah, if they're taking prednisone for months on end or even even just like a prednisone pack, they're going to have some adrenal suppression after that. 

00:05:20:11 - 00:05:40:01 

Mark Newman 

And you know what? That actually leads back into the high cortisol story. I think actually I want to stop and make sure that you can help people with this. I'm stressed, I'm inflamed, I make a lot of cortisol. That guy has an adrenal tumor or a pituitary tumor that's making HGH and I'm cranking out cortisol because of that. 

 

00:05:40:01 - 00:06:00:15 

Mark Newman 

So, Cushing's disease, right? Like how do you differentiate between someone who you need to calm them down and deal with stress and cortisol production and differentiate that from someone where you either need to do more work or you need to shut them off to your friend who's an endocrinologist to do a workup for Cushing's. How are you differentiating on the DUTCH test between those scenarios? 

 

00:06:00:19 - 00:06:19:22 

Kelly Ruef 

So, there's a tumor or there's good genes then then you'll lose your diurnal pattern again. So, you'll just have high cortisol throughout the day. A lot of times the nighttime or that bedtime, urine, cortisol or salivary cortisol is more than four times the upper limit. And then if you do an insomnia sample, a lot of times that's elevated too. 

 

00:06:20:00 - 00:06:23:06 

Kelly Ruef 

So, it just never it never suppresses and never comes down. 

 

00:06:23:13 - 00:06:50:18 

Mark Newman 

OK, and I think that four, four times is a nice number. And to be clear with people, when we dig through that, that's from the literature because we haven't tested enough people that have a confirmed tumor or whatever. But if you're looking at bedtime samples and you look at that upper limit and you're four times as high, maybe you're suspicious and then you're looking at the rest of the panel and if it's likewise like way up there at similar levels. 

 

00:06:50:22 - 00:07:13:02 

Mark Newman 

But the interesting thing with that is you you can sneak into the normal range in some of those early morning samples, which is why doing like a morning serum cortisol isn't that differentiating for something like Cushing's. But flat really high bedtime. And then those metabolites also really high is when you should start thinking about Cushing's as opposed to just a high cortisol producer. 

 

00:07:13:06 - 00:07:16:02 

Kelly Ruef 

Yeah, exactly. Then I started thinking, OK, endocrinologist. 

 

00:07:16:06 - 00:07:17:15 

Mark Newman 

Right, right. Time for some help. 

 

00:07:17:19 - 00:07:18:23 

Kelly Ruef 

Here comes my patient. Right. 

 

00:07:19:11 - 00:07:38:16 

Mark Newman 

OK, so those are kind of like the softball ones, right? Like the cortisol is high, the metabolites are high. This all makes sense. So, let's talk about the ones that end up resulting in people on the phone with you, which is when those tell a different story. So, we talk about the metabolites as being the best marker for overall production of cortisol. 

 

00:07:38:20 - 00:07:55:03 

Mark Newman 

And then the free cortisol tells us our stress response and that diurnal pattern of free cortisol. So, let's start with the free cortisol is low or relatively low and the metabolites are much, much higher. So now what are you thinking about in terms of what that means for a patient? 

 

00:07:55:12 - 00:08:20:18 

Kelly Ruef 

Yeah, so this is where providers have more difficulty. It gets a little more confusing. It's not as clear right right. But a lot of times when someone has low free cortisol but higher metabolize cortisol, right? Then you you often see that with obesity blood sugar issues, stress, inflammation, it could mean that they're metabolizing and clearing out their cortisol quickly. 

 

00:08:21:06 - 00:08:59:19 

Kelly Ruef 

And you can see that with hypothyroidism, for example. But if you go back to talking about people who are really overweight, it turns out that that fat tissue actually takes cortisol from circulation. So, the fat tissue kind of steals cortisol from circulation to use it for its own metabolic needs and then metabolizes it. So, a lot of times you'll see low free cortisol in circulation in the urine or the saliva, but high metabolites because the fat tissue is still using that cortisol and metabolizing it and there was a recent study, I think it was 20, 19 or 2020 where they showed that as your waist to hip ratio went up. 

 

00:09:00:08 - 00:09:05:11 

Kelly Ruef 

So, as you gain more and more weight, your free cortisol tends to drop. 

 

00:09:06:16 - 00:09:29:11 

Mark Newman 

OK, so, so if we're getting heavier, people are free, cortisol might drop a little bit which is really contrary to what a lot of people have said. Just in terms of general thinking about the relationship between cortisol and the weight gain and fat mass and that sort of thing. But then the metabolites themselves, the metabolites of that free cortisol, which again is a little lower, those climb really high in those cases. 

 

00:09:29:15 - 00:09:41:19 

Kelly Ruef 

Yes. Yeah, and it's it's it's unfortunate because like the fat tissue is getting a lot of exposure to cortisol, but since the free cortisol in circulation is so low, like that's what all the other tissues are getting that's what your brain is feeling. 

00:09:42:23 - 00:10:00:20 

Mark Newman 

Right? So, your brain's being told they don't have enough cortisol and, and you continue to produce it, but it continues to get siphoned off. Yeah. By OK, so you said overweight. What what were some of the other causes of this picture of clearing the cortisol such that there's a lot of metabolites and not very much free cortisol, obesity and. 

 

00:10:00:22 - 00:10:02:16 

Kelly Ruef 

Obesity, blood sugar issues, blood. 

 

00:10:02:16 - 00:10:03:03 

Mark Newman 

Sugar. 

 

00:10:03:06 - 00:10:21:02 

Kelly Ruef 

Inflammation, hypothyroidism. The way I remember it is you wouldn't want high cortisol and high thyroid hormones. You'd be so anxious your your bone health would be out the window. So gotcha. So usually with hypothyroidism you have a lower free cortisol. 

 

00:10:21:13 - 00:10:36:20 

Mark Newman 

Right? So OK, so it's cranking up the clearance of cortisol. If you have too much thyroid, which you see in people with something like graves and maybe more commonly in someone who's just overdoing it a little bit on the thyroid medication when they start off as hypothyroid. 

 

00:10:36:23 - 00:10:57:00 

Kelly Ruef 

Yeah, exactly. And the research, even shows with hypothyroidism, you tend to have like women tend to have higher androgens. And it makes sense because when metabolize cortisol goes up, you tend to see overall adrenal output going up and the adrenals and women especially make a lot of androgens. So, you tend to see androgens go up too. 

 

00:10:57:01 - 00:11:24:05 

Mark Newman 

Oh, that's interesting. I'm making more cortisol as a consequence. I'm making more DHEA, which then trickles down to testosterone and the other androgens. And um, that's, that's an interesting connection. Yeah. So, if we take that pattern and, and invert it and we have low metabolites, which imply low production, yet the free cortisol is not also low, maybe it's normal, maybe it's high, but it's this picture of not getting rid of your cortisol, not metabolizing your cortisol. 

 

00:11:24:20 - 00:11:28:05 

Mark Newman 

What sort of patients in clinical pictures tend to look like that? 

 

00:11:28:14 - 00:11:39:21 

Kelly Ruef 

Yeah. So, with that you tend to see it with hypothyroidism, and you tend to see it with things that slow down metabolism rate. So, hypothyroidism we know low thyroid slows down metabolism. Right. 

 

00:11:39:21 - 00:11:40:11 

Mark Newman 

That makes sense. 

 

00:11:40:20 - 00:12:09:02 

Kelly Ruef 

But also, low calorie intake, even anorexia. I look at how much patients are exercising relative to the calories that they're taking in. Besides that, we've got sluggish liver clearance and poor mitochondrial function because you need that ATP need that energy for metabolism. And I even think about medications like finasteride because finasteride we know is a five alpha blocker and those five alpha enzymes are involved in cortisol clearance. 

 

00:12:09:05 - 00:12:12:23 

Kelly Ruef 

So, I wonder about these medications and their effect on cortisol clearance. 

 

00:12:13:02 - 00:12:36:05 

Mark Newman 

You don't know how much you see that in the literature, but I do know we had 11 case so you don't want to build too much of a case on an anecdote, but a gentleman who had really, really high free cortisol, a lot of anxiety and things related to that but then his metabolites were super low. And so, then when you flip back to the androgen page, you see this just hard core five beta metabolism of the androgens. 

 

00:12:36:12 - 00:12:58:14 

Mark Newman 

But those drugs are not that selective, right? You have, I think two different types of five alpha reductase enzyme. Maybe there are more than that, but those, those drugs block five alpha, well they also block five beta two is to a lesser degree. So, it seemed like for that particular gentleman that that the medications were just hammering that enzyme or enzymes. 

 

00:12:59:03 - 00:13:09:16 

Mark Newman 

So, there's cortisol just couldn't clear and get out of the way even though it wasn't making very much it really high cortisone it seemed like for him the causal thing was was potentially that the medication. Oh yeah. 

 

00:13:09:16 - 00:13:10:22 

Kelly Ruef 

That's interesting. Yeah. 

 

00:13:11:11 - 00:13:34:01 

Mark Newman 

OK, so we've talked about what some of these different patterns look like in terms of cortisol metabolites. Part of the confusion I think that people have oftentimes is we're measuring when we say metabolize cortisol, it's tetrahydrate cortisol, tetra, hydrocortisone. They're they're not that interesting in and of themselves. They don't have clinical impact, but they're sort of like the bucket at the end of the day that catches all of the cortisol that you make. 

 

00:13:34:01 - 00:13:52:06 

Mark Newman 

And we can infer some things from those. Cortisol is the active form. Cortisone is the inactive form, but it's also a metabolite. So that gets really confusing. I think sometimes in terms of the lingo. So, can you explain for us what like what cortisone is and how it relates to cortisol? 

 

00:13:52:12 - 00:14:16:13 

Kelly Ruef 

Yeah, definitely. So, as you said, free cortisol is the active form. Free cortisone is the inactive form. And for some reason dodgeball comes to mind. And I just think of Ben Stiller and Vince Vaughn on the sideline but basically cortisone is like the guys on the sidelines in dodgeball, and cortisol is the active form. It's the guys that are actually in the game playing. 

 

00:14:17:06 - 00:14:38:23 

Kelly Ruef 

And so, cortisone, what's unique about cortisone is even though it's inactive, it can become active. So those players on the sidelines can go into the game and start playing, right? And so, cortisone can be activated to cortisol in the tissues and it's a great way for the body to regulate active cortisol levels in the tissues. 

 

00:14:40:01 - 00:14:49:20 

Noah Reed 

So, on the left chest, we have this little fan that tells us you're either preferring cortisol or cortisone. What story is that telling? If I'm preferring one over the other? 

00:14:50:06 - 00:15:22:04 

Kelly Ruef 

Yeah, that's a really good question too. A lot of people look at the graphs, so they look at the urinary free cortisol and cortisone graphs or the saliva graphs when they're looking at the balance between cortisol and cortisone, it's systemically, but we don't want to do that. We just have to keep in mind that when we're looking at the free cortisol and free cortisone in the urine and the saliva, we're looking through the window of the kidneys and the salivary glands and there's an enzyme that lives in the kidneys, in the salivary glands that can affect the balance of free cortisol and free cortisone. 

 

00:15:22:22 - 00:15:48:07 

Kelly Ruef 

What we want to do when we want to see the systemic balance, we want to look at the metabolites. So, we know that when the body's done with free active cortisol, it metabolizes it to chef. And when the body's done with inactive cortisone, it metabolizes it to THC and cortisone. And THC both end with an E, so it's easy to remember, but you want to look at that fan gauge on the DUTCH test. 

 

00:15:48:07 - 00:16:03:18 

Kelly Ruef 

So, if they're there, be engaged, just push in more towards the T f, the cortisol all metabolites, then we know systemically they probably have more in the form of cortisol in the active form when it was metabolized and vice versa. 

 

00:16:04:00 - 00:16:27:11 

Mark Newman 

One of the annoying things about biochemistry and cortisol is everywhere we go hunt for cortisol in the place that gives us that sample. There is metabolism from the active cortisol to cortisone, not in the other direction, right? So, we see that there is a diagonal pattern of cortisol and also a diurnal pattern of cortisone. And that's because both of them are in those concentrations. 

 

00:16:27:11 - 00:16:49:11 

Mark Newman 

But it's also because in the saliva gland, cortisol gets pushed to cortisone before it comes out in your saliva. And well then let's let's go look at urine. Well, in the kidney it's the same thing, the kidneys trying to keep cortisol off that aldosterone receptor, so it doesn't raise your blood pressure too much. So, in that before it spills into the urine, some of that cortisol gets converted, converted to cortisone. 

 

00:16:49:16 - 00:17:13:06 

Mark Newman 

And so, we see them both. But the consequence of that is because there's this localized conversion when you want to ask the question, OK, is is Noah's cortisol or cortisone, which one’s sort of winning that big tug of war? You don't want to look at cortisol and cortisone as the primary way of asking that question. You look at the metabolites, so do I flood more tetrahydrate cortisone or do I flood more tetrahydrate cortisol? 

 

00:17:13:09 - 00:17:36:23 

Mark Newman 

So, we look at the ratio of those and if it's tilted in one direction, it implies that in your systemic overall tug of war, it's favoring active or favoring inactive. And the use of the cortisone itself is just to confirm that up and down pattern because you will see. So, because mostly you go to a different lab and you get tested, all they give you is cortisol and most of the time that tells you the story, right? 

 

00:17:36:23 - 00:17:56:11 

Mark Newman 

And then you see these oddball cases every once in a while, where cortisol, let's say, has is low, normal, this nice little picture. And then you look over at cortisone and it's out of range high and you say, well, what does that mean? Well, it means in that particular tissue that a lot of that cortisone that you're staring at like seconds before it went into your sample used to be cortisol. 

 

00:17:56:16 - 00:18:14:23 

Mark Newman 

So, I think of it as like a shadow of cortisol. It's like the shadow of the shadow is telling a very different story. You kind of need to pull your interpretation in that direction. And, you know, we wish it was this easy paint by numbers stuff, but you know, in most of the time they align really well. And in that case, it's just confirmatory. 

 

00:18:15:03 - 00:18:31:01 

Mark Newman 

But when they tell a little bit of a different story, that's when you get on the phone with Kelly and say, Kelly, help me with this. You know, what does this mean? So, so the cortisone and cortisol tell an interesting story, but they do also bring some complexity to to the case as well. 

 

00:18:31:07 - 00:18:52:10 

Kelly Ruef 

Yeah, they do. But a lot of times I'm like, well, I'm so happy that we measured the cortisone because we would have missed all this cortisol. We only looked at the free cortisol, we would have missed all of that free cortisol that got deactivated in the salivary glands in the urine and went to cortisone. So yeah, having that additional free cortisone graph can really help. 

 

00:18:52:10 - 00:18:53:09 

Kelly Ruef 

Just add to the picture. 

 

00:18:53:18 - 00:19:10:17 

Mark Newman 

One of the other I think patterns that's interesting is what you do with somebody who the free cortisol is not high, it's like stupid high, right? And then you look at the cortisone and you think, oh my gosh, they have Cushing's disease or whatever. And then you look over at the cortisone and you see a relatively normal pattern. 

 

00:19:10:20 - 00:19:24:15 

Mark Newman 

So, what do you typically tend to think of when you see and of course I'm sort of setting you up for four for this one, but when you see those stupid high cortisol and then a relatively new normal cortisone, what does that tend to imply for our patients? Or what's the first question you're going to ask? 

 

00:19:24:21 - 00:19:31:11 

Kelly Ruef 

OK, so the first question you ought to ask is, is this contamination is this hydrocortisone cream contamination for. 

 

00:19:31:11 - 00:19:42:02 

Mark Newman 

Hydrocortisone mean and this gets confusing is cortisol. Yes, right. Cortisone hydrocortisone. Sometimes people think, oh, its cortisone hydrocortisone is cortisol, actually cortisol. 

00:19:42:02 - 00:20:04:11 

Kelly Ruef 

OK, so if you put hydrocortisone cream on a rash and then you touch your touch sample paper, it's going to affect the free cortisol. But the beauty of it is it doesn't affect the free cortisone because that hydrocortisone cream would have to get into your body to be then deactivated to cortisone to show up on the the cortisone graph. 

 

00:20:05:05 - 00:20:18:18 

Kelly Ruef 

So, if the cortisol, the free cortisol is really high or there's no diurnal pattern, it looks wonky, but the cortisone still has that diurnal pattern. Then we look at the cortisone to get the data, to get the information we want. 

 

00:20:19:01 - 00:20:46:17 

Mark Newman 

And the nice thing about that is if you can actually confirm, be confident that it's contamination and not some really weird crazy tumor in metabolism pattern if you can confirm that, it's that they're using hydrocortisone. There are actually papers that show that looking at cortisone itself is a good surrogate for your diurnal pattern of cortisol. So that's that's why we spend the extra money to get mass spectrometers so that we don't just get cortisol, we get we get cortisone. 

 

00:20:46:17 - 00:20:57:22 

Mark Newman 

And again, a lot of times it just confirms the story you're already looking at. But occasionally it sort of comes in there and saves the day. And contamination with hydrocortisone is one of those situations oh yeah. 

 

00:20:57:22 - 00:21:03:14 

Kelly Ruef 

I'm always look at the cortisone graph. I feel like it adds a lot of value to the test for a lot of people. 

 

00:21:04:01 - 00:21:19:13 

Mark Newman 

And then the caution with that is just not overinterpreting that right of not allowing that in your mind to represent that patient's overall cortisol cortisone balance for that. As you mentioned, we defer to the metabolites and the message that they that they the the story that they paint. 

 

00:21:19:21 - 00:21:32:10 

Kelly Ruef 

Exactly, exactly. I keep it simple. I say, do you want to know the balance of cortisol and cortisone in your urine or your saliva? Then look at the graph. If you want to know the balance of cortisol and cortisone systemically in your body, look at the metabolites. 

 

00:21:32:18 - 00:21:54:18 

Mark Newman 

That's a really nice way to say it. And in doing so, you've you've brought us through from up and down patterns of cortisol, cortisone, metabolites, like there's a lot there. So, tell us just for you, as you see one set of results and you're going to sort of work your way through that. I tend to think of it in terms of like a hierarchy of information and what it tells you. 

 

00:21:54:20 - 00:22:05:11 

Mark Newman 

Like how do you like literally work your way through the adrenal portion of a DUTCH complete or a DUTCH plus, like how are you mentally digesting that? 

 

00:22:06:00 - 00:22:33:13 

Kelly Ruef 

Yeah, that's a good question. So, the first thing I do is I look at the metabolize cortisol and the total androgen output, total adrenal androgen output or the total DHEA. A lot of times the metabolize cortisol, of course, will tell you overall adrenal output of cortisol. And it can tell you how hard the adrenals are working. Right. And if you see a high metabolize cortisol and a high DHEA, then, you know, OK, the adrenals are probably just working overtime, right? 

 

00:22:33:20 - 00:22:53:11 

Kelly Ruef 

So that can give me an idea of overall total production. And then after that, I look down at the graphs at the free cortisol and the free cortisone. And the first thing I ask is, is there a diurnal pattern or is it flatlined? Is it flatlined? But really, you know, really, really low like Addison's or when people use prednisone or other glucocorticoids or is it kind of flatlined? 

 

00:22:53:11 - 00:23:17:11 

Kelly Ruef 

But really, really high, like perhaps with Cushing's disease, which is not always flatline but doesn't have that terrible pattern. So, if they have a diurnal pattern, you know, that's great. And then I kind of look at, well, is it within range or is it a high diurnal pattern? Is it a low diurnal pattern? So that can give you a little more information about the active cortisol in circulation, like what are the tissues feeling? 

 

00:23:17:22 - 00:23:47:16 

Kelly Ruef 

And the third thing I do is I look at the kind of the balance or the ratio between metabolize cortisol and the total free cortisol, the total free cortisone. And usually, you want those dials to kind of line up point in the same direction and both be within range. Then, you know, you don't have any metabolism issues. But like we said earlier, if we have a high metabolize cortisol in a low total free cortisol, then we might be clearing our cortisol out quickly. 

 

00:23:48:05 - 00:24:10:23 

Kelly Ruef 

And the same is true with the opposite, you know, low metabolize cortisol, high total free cortisol. We might not be metabolizing our cortisol out well enough, you know, might be kind of sluggish. And then of course, after that, I look at the dial to see the tag and have preference, which tells you systemically, is there more cortisol in the active form or in the inactive form? 

 

00:24:11:04 - 00:24:35:22 

Mark Newman 

So early on, your kind of looking at if you think of in terms of like a tug of war, the free cortisol and the metabolites of cortisol. And if those tell the same story, then you have sort of a simplified job of sort of telling this patient story. And then if they tell different stories, then you either have a story of increase or like sped up cortisol clearance, like rapid cortisol clearance or sluggish cortisol clearance. 

 

00:24:35:22 - 00:24:48:11 

Mark Newman 

And then you just have some additional questions to ask about what's driving the upregulated or down regulated processing of cortisol. So that seems like a pretty intuitive way to go through that. I like that. 

 

00:24:48:18 - 00:24:50:12 

Kelly Ruef 

Yeah. Yeah. Works well. 

  

00:24:51:06 - 00:25:09:02 

Mark Newman 

Well, we know that one of the challenges that our providers have when they onboard with us is just that the test is comprehensive, and that's a lot to wrap your head around. So really appreciate you coming and taking this complex topic of cortisol and the patterns that we see and distilling that down for for our providers so they can make sense of that. 

 

00:25:09:02 - 00:25:16:04 

Mark Newman 

And we know if they don’t, they can always get on the phone with you and your team and you guys do a great job. So, thank you for coming and explaining that to us. 

 

00:25:16:04 - 00:25:18:05 

Kelly Ruef 

Yeah, you're welcome. My pleasure. Thanks for having me. 

 

00:25:18:05 - 00:25:18:18 

Mark Newman 

Thanks, Kelly. 

00:25:19:05 - 00:25:44:12 

Noah Reed 

Kelly, thanks so much for joining us again on the podcast. I know this conversation will help a lot of our providers and thank you to all of our listeners. Your support has been amazing and we're so thankful for liking subscribing and sharing that you're listening on social media. If you're not already following us on Instagram, our handle is at DUTCH Test, and we'd love for you to tag us and to post and share something that you've learned so far from the podcast. 

 

00:25:44:15 - 00:25:56:13 

Noah Reed 

So, stay tuned for next week's episode where we continue our endocrine Essentials theme and speak with Dr. Alison Smith about oxidative stress. I'm Noah Reed, until next time.