(Scroll down to see video transcription.)Dr. Clark is leading a 3-day program titled Mastery of Neurochemistry of Male & Female Hormones on Dec 7-9, 2018 in Cape Canaveral, FL and via internet live-stream. Click the image below to learn more! Video Transcription – Hello, welcome to CITV. Today we’re joined by Dr. David Clark, and we’re doing a video case review. Dr. Clark, how you doing? – I’m excellent. – Awesome. What’s the topic today? What do we have going on? – We’re going be doing a case walkthrough on a 20-year-old female with headaches and looking at how we use neurochemistry to figure out what’s wrong with her. – All right, let’s jump into it. – Let’s do it. All right, so her name’s Angela, not her real name. Let’s just go with her chief complaints, and this is it. This is her chief complaint, you ready? If I can get my little remote dude to work. It’s apparently not gonna work. Just a second, oh. Hold on, there it is. Now we’re working, technical difficulty solved. She has headaches with exertion. Let’s start with that. What do you think? I have to pick on you, because I can’t hear what anybody else is saying. – Yeah, you can’t harass anybody else. So headaches with exertion, you gotta do a cardiovascular exam, and I would actually be worried about blood flow in the head as well during exertion. So you kind of wanna palpate some of the pulses up there and see if there’s any changes. Also, start thinking autonomics, because of blood flow. – Autonomics for sure. You know it’s definitely gotta be. Headaches are just always autonomic, unless there’s some kind of space-occupying lesion, right? She has headaches often when waking, though. So not just when she’s exerting herself, just when she wakes up in the morning. What do you think about that? – Well, still could be autonomic, ’cause you’re dealing with a different blood flow requirement when you’re horizontal at night versus upright, but it takes me away from POTS a little bit, ’cause she’s been there. – It takes you away from it a little bit, right? – Yeah. – Now, I’ll just tell you, classically speaking, from like a metabolic standpoint, when someone has headaches with exertion, headaches when waking, the first thing I think of it’s some kind of hypoglycemia, right, slash, I’m kinda giving away the farm, I guess, but not really, some kind of adrenal gland hypofunction, okay? Because those adrenal glands are supposed to make cortisol. They’re supposed to make adrenaline, and when you have headaches with exertion and headaches when waking, from a metabolic standpoint, the first place you go is, something going on with glucose, possibly adrenal glands. Now, as you just said, from a neurological circuit standpoint, which, I view everybody from that lens too, I go, autonomics, right? What’s going on with her autonomics when she exerts herself? Is it too much sympathetic? Is it not enough sympathetic? You don’t know, but you know there’s some kind of category of some kind of dysfunction with that. So, from a circuit side, we’re thinking autonomic dysfunction, maybe POTS, who knows. From a metabolic side, most suspicious about some kind of adrenal problem. That’s all of her complaints, that’s it. – Oh. – All right, so her history. She’s a junior at Harvard. She’s 20. She’s had two concussions. She had one during her junior year of high school, a pretty good one, and then a second one during her sophomore year of college. So, concussions. Does that change our mind about any of her symptoms? Does it point us in one direction or the other? Not really. I mean, she could certainly have POTS after a concussion. That happens plenty of times. She could certainly have adrenal gland dysfunction because of hypothalamic pituitary adrenal disturbance. That happens all the time with concussions too. So, it doesn’t really, you know, we don’t know yet. Now, generally, she rates the headaches as a three of 10, which you and I might not think it’s that big of a deal, but she basically has them every day, and she’s tired of ’em, and sometimes, she’ll just have them randomly through other parts of the day, not just when she wakes up. Now, interestingly, and I think I put this next, yeah, if she takes a nap in the afternoon, she’ll wake up from it with a headache, which I’ll just go ahead and tell you, that little bit always kinda bugged me, ’cause I thought, what the heck is going on with that? Why would that be? It’s gotta be some of the same mechanisms versus when she goes to sleep and wakes up in the morning. It’s gotta be the same sort of mechanism when she’s going to sleep and waking up, and it’s gotta be autonomic in some way. Like you said, there’s gotta be something that I just don’t know what it was. Now, she’s been diagnosed with POTS, okay? Now, she also, whoops, left that out, last bullet, she’s also already had, before coming to me, two week-long intensive receptor-based rehab treatments with some people who know what they’re doing, okay? So, the circuit side of things was already looked at and dealt with. So now she’s referred to me because maybe there’s some kind of metabolic issue that hasn’t helped, it’s been kind of a sabotage or an obstacle for her getting better, okay? So this is it. It’s not a super complicated history. She has been taking fish oil, when I’m seeing her, vitamin D, resveratrol, turmeric, and magnesium. All that is perfectly reasonable based on her symptoms, right, assuming that she might have some sort of inflammatory problem. You know, magnesium is often good to help downrate NMDA receptors, you know? That’s all fine. It’s not helping. I mean, it’s not really doing the job. Otherwise she would be not seeing me, but you know, that stuff’s fine. I’m not worried about any of that stuff. She’s also taking birth control. Now, I’m gonna put that in here, because we’re talking about hormones, right? Now, this particular birth control is a progestin, and that’s what desogestrel is. That’s a progestin, and ethinyl estradiol, which is obviously a form of estrogen. And there’s the dosages of it. It’s kind of a progesterone-heavy birth control, and here’s how it works. It works by stopping ovulation. Now, I’m not gonna have time to jump into all the normal stuff that goes on with the menstrual cycle, but I can just tell you, that’s how most birth control pills work, is they disrupt ovulation. If I give you more hormones than you normally secrete, then the cycle backs up, and we stop ovulating. If you don’t ovulate, there’s no egg that’s available there to be fertilized during intercourse. So that’s how most birth controls work, and that’s how this one works, all right? Now, in the recent past, she couldn’t go more than a couple of hours without eating, but now she can go about four hours without eating. Now, that right there tells me, yeah, she’s had an adrenal gland problem. She’s had a problem with reactive hypoglycemia, and I’m just gonna say a point about that. I don’t even really like that term, hypoglycemia, because by definition, you’re saying low glucose in the blood. But a lot of people don’t actually have low glucose in the blood. When you check ’em, they’re not actually hypoglycemic on labs. But they are tissue hypoglycemic, if you will, meaning the glucose is there; they’re just not getting it into the cells. It’s the same thing that happens with someone who’s insulin resistant, someone who’s type II diabetic. The glucose is there, it’s just, it can’t get into the cell because they’re resistant to the signal of insulin, and so they don’t transport it. That exact same thing happens with people who are hypoglycemic, okay? – Mmhmm. – It’s just that there’s not really a term that I know of that would describe that. So I’ve kind of started calling it hypoglysomic, right, or some kind of made-up word. Just so you guys know, you have to be careful about the terminology you use, but sometimes, there’s not terminology that exists to describe physiologically what we’re talking about. Now, she’s had some down feelings, a little more depression. She thinks it might be related to hormones. Doesn’t say why, she just thinks it might be related to hormones. All right, so her diet is significant for being gluten-free and dairy-free, because she’s been diagnosed in the past with Irritable Bowel Syndrome. And she’s avoided some what we call higher FODMAPs foods because she feels like they make her feel a bit worse. I think that’s interesting, because Irritable Bowel Syndrome in some people is an actual autoimmune condition, and for me, that kind of lights up my radar a little bit. So she’s gluten-free, dairy-free. That’s cool. There’s not much more I would wanna do with her diet anyway. She’s already avoiding two extremely potentially inflammatory foods. So that’s it. There’s not a lot going on. She’s taking a few things. She’s taking birth control pills. She feels a little down occasionally. She’s on a gluten-free, dairy-free diet already. She might have some IBS. She also drinks coffee, which, for someone that has an adrenal gland problem, that’s the last thing she should be doing, is drinking coffee, ’cause what that’s gonna do is force her adrenal glands to respond metabolically, and that’s not something she should be doing. I can tell you, I told her to stop doing that. – Hmm. – So what’s our impression? What do we think’s going on with her? What’s your idea? What do you think so far? I mean, is there any clear ideas that you have? – Super clear? I don’t see it yet if it’s there. – Yeah, I don’t either. I mean, there’s not much there. So we’re gonna have to do some investigation, right? So, she has an IBS diagnosis. She has a POTS diagnosis. She might have that reactive hypoglycemic thing going on. She wakes up with headaches. That’s pretty good evidence for that. The headache after a nap, I’d never heard that before, but I still think it’s probably related somehow to that adrenal problem. Now, the birth control pills. Does it matter in this case that she’s taking them? What do you think? – There’s nothing that makes me think it would yet, but I need to know a little bit more about her hormone stuff. – Fair enough. – To make that decision. – So where do we start? A lot of places we could start, right? We should test for mercury, right? – I probably wouldn’t start there. – Yeah, where is there an indication that we should test her for mercury, right? But the thing is, some people, and perhaps some of you guys watching, would probably go out to left field and start to shoot for something, and maybe you get lucky with that. But just remember, try to base your testing on what seems to make sense with that case. I know that’s kind of a broken record with me, but I’ve been to the place where you test everything. I’ll do $3,000 worth of tests, and whatever shows up, that’s what’s wrong, and that is gonna get you into trouble, ’cause number one, you spend all their money, and they don’t have any money left for treatment. And number two, just because something’s abnormal on the test doesn’t mean it has anything to do with her headaches, right? There’s no guarantee that if you find mercury, that it has anything to do with her headaches. There’s no guarantee if you find out she has candida that it has anything to do with her headaches. So there’s never a guarantee that what you find abnormal matters. Now, we could do receptor-based rehab, except that’s already been done, right? Somebody already did that. Somebody skilled’s already done that a couple times. So we’re going with metabolic. So, remember, we’ve got four kind of neurochemical priorities, and the number four one is GI and liver. Does she have any overt GI and liver symptoms? No, she does not. She does not have any GI or liver symptoms. Does she have an adrenal or blood sugar? Very likely. Now, that’s definitely a possibility for her. Does she have any red blood cell abnormalities? Well, there’s no way to know. We have to check her red blood cells before we’ll know that. And then number one, does she have any kind of autoimmune problem? Well, we don’t know yet. Now, for me, as I’ve told you guys many times before, that autoimmune question is the number-one question I wanna answer, because very simply, if she has a clinically significant autoimmune problem, there’s a very good chance that it is creating problems with number two, three, and four, and if we just go down here and treat two, three, and four and never go after number one, you don’t get anywhere. You just don’t get anywhere. So what are we gonna do? What tests are appropriate for this case? Well, it depends on a couple of factors, as I was just saying. Number one, what are you gonna get out of it if you do it? I mean, do I need to test everything in the world in order to find out what’s wrong with her? No, so we call it the clinical yield. What information is it going to give you that is usable? It’s like if a person comes into your office, and they have a headache. Do you immediately go run an MRI on ’em? – No. – Probably no. I mean, that’s a little bit ahead of the game, right? Don’t need to do that right yet. Now, there’s also logistics. There’s also the patient’s budget, which I think more people should take into consideration, frankly, because you know, some of these people that are sick, and they’ve already spent a lot of money, right, they don’t necessarily have a lot of money left when they see you. So try to be economical and be humane about it, right? So with her, she has headaches. They most closely resemble reactive hypoglycemia, which would be an adrenal problem. It could be B vitamins. But look, there’s a lot of different possibilities for the etiology of her headaches. I mean, there just are. So we’re gonna have to try to rule some things in, rule some things out. There’s inflammation, but look, she’s already taking turmeric and resveratrol and vitamin D. She’s doing a gluten-free, dairy-free diet. You would think, if it’s an inflammatory etiology, perhaps that would have helped. Could be nutrient deficiencies. Could be, again, B vitamins. Iron deficiency can cause headaches for sure. Could be anemias. Could be hormonal aberrations. Thyroid hormone aberrations can make you have headaches, but there could also be aberrations in hormones such as the sex hormones, estrogen, progesterone. Those can cause headaches, those can cause headaches. The blood chemistry, what are you gonna order on her? Well, we’re gonna a comp metabolic, a lactate dehydrogenase, because that’s kind of the surrogate test to tell us about her tissue glucose, a CBC with diff, lipid panel, homocysteine, hemoglobin A1c, looking at blood sugar, looking at her iron/IBC, her ferritin, vitamin D, B12 and folate, and one of the reasons I’m checking these is she’s taking some of this stuff, and I need to find out if she’s absorbing this stuff that she’s taking, ’cause that can be a clue into part of what’s going on with her as well. We’re gonna look at B12 and folate. We’re gonna look at her high-sensitivity C-reactive protein, which is an inflammatory marker. Don’t make the mistake of thinking to yourself, if the patient’s inflamed, the high-sensitivity CRP will be elevated. If she’s not inflamed, it won’t be elevated. That is not gonna serve you. That’s very much too simplistic. And we’re gonna look at her thyroid panel with antibodies. There’s what I think is a thyroid panel, because if she’s hypothyroid or has some different varieties of thyroid malfunction, that can cause her headaches, absolutely, and there’s no way to know about it unless you test it. You’ve gotta check it to see, and I’m interested in Hashimoto’s, because I’ll be honest, these days, it’s almost like who doesn’t have Hashimoto’s, ’cause it’s the most common, the most common organ-specific autoimmune condition, is Hashimoto’s, and head injuries are incredibly inflammatory, and they love to turn on problems with autoimmune conditions. So again, that blood work’s gonna give me some windows into blood sugar/tissue sugar, relevant nutrients, anemias, thyroid, and some inflammatory markers. All right, now, I wanna look at her hormones, all right? I’m gonna do DUTCH testing. You can do whatever you want. I like to use DUTCH testing, sometimes combined with some blood testing. DUTCH testing is an acronym, and this is one of the things we’ll be talking about in detail. In fact, this whole thing that I’m telling you guys, we’re gonna talk about this in a lot of detail in the class that’s coming up in December. So DUTCH testing stands for dried urine testing for comprehensive hormones, and by doing that, I get to look at the following markers. I get to look at androgens, which are what these guys are, DHEA, testosterone, these guys. All of those are androgens. I get to look at the three estrogens. I get to look at progesterone metabolites, which tell you about progesterone, and if I do the adrenal part of it, I can look at free cortisol, cortisone, and something that’s really important that you might not have heard of before, metabolized cortisol, because I’m gonna tell you guys, I have done many, many, many, many adrenal salivary profiles, and yeah, they are reliable to measure free cortisol. That’s not the issue. The issue is, is free cortisol really what matters? I’m gonna tell you, no, it is not the only thing that matters, and running a free salivary cortisol test as your indicator of adrenal function will disappoint you, because it is not the whole story. Metabolized cortisol, I’ll talk about this later when we get to the class in December, that is a much more helpful marker, because it really reflects what’s going on, really, not just the free value. All right, that being said, this just happens to be what her DUTCH results look like. And I don’t want us to analyze these right now. I just wanna show you, this is kind of graphically what those DUTCH results look like. So if you’ll see right here, pregnenolone is kind of the mother hormone, and it can go down this left-hand pathway and become progesterone and ultimately cortisol and aldosterone, or it can go down this right-hand pathway and become androgens first, and then from androgens, we get estrogens. Now, a lotta people don’t know that. You get estrogens from androgens, and that actually is really important when we start talking about conditions like PCOS or polycystic ovarian syndrome, and again, that’s one of the things we’ll be talking about in the class. That’s just kind of visually what it looks like, and we’ll talk about what those mean with her in just a sec. So, does she have an autoimmune problem? We haven’t answered that question. We’re gonna do some blood chemistry. We’re gonna do some DUTCH to look at some hormones, but does she have an autoimmune problem? We don’t know that, really. There’s a couple different ways we could figure that out, and I’ve talked about this before. You know, you could know the specific antibody that’s involved if she’s got it, or you could know that she has some autoimmune problem in general, and there’s disadvantages and advantages to both of those. So antibody testing is something you could do, but look, it’s specific, but it’s pretty expensive. I mean, like, I don’t know what antibody would you check for in this girl. I don’t know. You could check for any hundreds of things. A lot of people have fallen in love with the Cyrex Array 5 test, and that’s fine. It’s a great test, no problem. But just because they don’t have something on that panel doesn’t mean that they don’t have an autoimmune problem. Is that enough double negatives? So what that means is that test is 24 different antigens or antibodies, but that’s not everything. That’s why I say it’s not encyclopedic. So, you’ve gotta realize going in, that’s 24 things. That’s not all the things that a person can have. So, you just gotta not oversell that test to yourself, and certainly don’t oversell it to your patient. It does have its place, though. Now, you could do something called a clinical challenge, which is what we did with this girl, and a clinical challenge is interesting, because my computer’s frozen. Why is it freezing when I get down to the bottom of every one of these slides? All right. This is like, the most ridiculous thing ever. Here we go. All right, so with the clinical challenge, it is cheap, it only costs about 20 bucks to do it, but it’s not specific. It’s gonna give us a general indication that the person has an autoimmune problem. It doesn’t tell us the name of it. But, from a treatment standpoint, that’s not all that important in a lot of ways, to know exactly the name of it, because all these different autoimmune conditions get different names, but biochemically, they’re all very similar, so from a treatment standpoint, I just gotta really know, does she have an autoimmune problem? So, we can have her ingest, take, for a couple of days, some Th1, some T Helper 1 cytokine stimulators, and see how she reacts. Does it make her worse? Does it make her better? Then we can have her take some T Helper 2 cytokine stimulators and think, hey, does that help, or does that make it worse? Now, there are, you guys please don’t go out and do this on your own, ’cause if you don’t know what this is and I haven’t taught it to you, don’t go do this. There’s real specific rules you have to follow, and in her case, I felt like we could do it. I was very upfront with her, full disclosure about what I’m really looking for, is does it make her feel worse, but please don’t go do it on your own if you haven’t really taken a class where I’ve explained it to you, because there’s some situations where you would never do this, okay? Now, we did that with her. She had an unclear reaction to it, right? Like, neither one of ’em really made her feel worse, but maybe she was worse with T Helper 1. So, you know, I can’t really get excited about her reaction to that. All I can really do is say, hmm, I wonder if she is even capable of having a reaction to that. So how do we figure that out? Well, if her white blood cell count is normal, I’m gonna show you that in a second, and she has no reaction to the immune system challenge, it’s a pretty good indication that there’s not really an autoimmune issue at play. Does that makes sense? ‘Cause what we’re doing is we’re taking the bee hive, and we’re like shaking the bee hive up and saying, hey, is there any bees gonna come out and sting us if we do this? Well, if her white blood cell count is normal, which is the bee hive, and she has no reaction to us shaking it, you know, her immune system probably doesn’t play that big of a factor. Now, if her white blood cell count happened to be less than five, that means the bee hive is not really strong enough to have a reaction anyway. So, she didn’t really have much of a reaction. I’m gonna go look at her blood work in a second and see where her white blood cell count was to see, hey, could she even really have a reaction? So what did we find out? Well, her white blood cell count was 4.7, which is a little bit lower than five. So that could be why she didn’t really have much of a very clear reaction to it, right? Now, the question is, why does her white blood cell count look like that? Well, it could be just normal for her. That may not actually be a problem or signal anything wrong. It can also, your white blood cell count can go down a little bit if you have a chronic autoimmune problem, because the cytokine soup that you get from that likes to suppress your bone marrow a little bit. So that’s a possibility as well. So, you know, I’m kind of hemming and hawing in my mind right now, going I don’t know. I mean, maybe she might have an immune system component, but I’m kind of 50-50 on it, right? Nothing super strong. Now, her lymphocyte percentage was a little bit high, and everyone looks at that and says, oh my God, she has a viral problem. Maybe, you know, that’s a possibility. Lymphocytes being a little bit elevated but nothing else being abnormal in terms of her differentials, I wouldn’t get too excited about that. I mean, you could say that this right here, those two guys right there indicate a viral problem. That’s kind of a stretch. Maybe she had a cold, you know? So it doesn’t mean we have to go, now we gotta treat her for a virus, right? I don’t think that’s very reasonable in this case, based on those results. Her BUN’s a little bit low. Her anion gap’s a little bit high, which means she’s a little bit acidic. Her carbon dioxide’s a little bit lower than I like to see, which means she’s probably a little acidic. Her B12, I don’t like that value. Now, again, B12, the blood test, is not a great test for B12 levels. Number one, it’s just not that great. You can use a methylmalonic acid to give you a better indication of what her B12 levels really are, but I will tell you that the literature says that, excuse me for a sec, the literature says that if your B12 is less than about 500 or 550, you could probably benefit anyway from taking B12, and of course there’s another problem with B12 if your B12 is high, but you’re not taking B12, which I’ll talk about at some other point. You with me so far? – Yes, sir. – All right, cool. And her D is 63. That’s a pretty good level for D. I’m okay with that. You know, she’s been taking vitamin D. She’s absorbing it; sounds good. Her LDH is a little bit low. Now, LDH is that enzyme that we use as a surrogate that kind of tells us about someone’s tissue glucose status, and kind of the marker, the cutoff I use is 140, and if their LDH is less than 140, probably dealing with someone that has that tissue reactive hypoglycemia thing, especially if they have symptoms that correlate with it as well. And again, the source of that is usually an adrenal gland hypofunction. Ferritin 95. That’s definitely not low. It is almost getting into the suspiciously high range, because ferritin is an acute phase reactant, meaning ferritin will elevate if you’re inflamed. Not all the time, but very often, it can inflame. I mean, it can elevate from inflammation. TSH, that’s fine. T4 17, that’s high. Her T3 182, that’s high, real high. Her T3 uptake is low, 20% is low. Reverse T3, 31, that’s high. So, something is going on with her thyroid panel. I can just tell you, something is weird here, because I don’t know if you, lemme ask you. Well, lemme see. I don’t remember what I’ve done here. Excuse me, her free T3 is fine, and her free T4, excuse me. Her free T3 is fine, yeah. Her free T3 and free T4 are fine, nothing wrong with those. But her total T4 is goofy, her total T3 is goofy, the T3 uptake is goofy, the reverse T3 is goofy. I’m just gonna tell you, that doesn’t many any sense, because if her T4. – Yeah, I can’t distinguish the pattern. – You can’t, ’cause there isn’t one. That is not a pattern. That doesn’t mean, don’t you dare tell me that’s a conversion problem, ’cause it’s not. That is a weird, weird pattern, because if her T4 was that high, her TSH should be low, and it’s not, okay? And plus, the free value isn’t high, right? Now, I will tell you this. This guy right here, this T3 uptake, may be why these guys don’t look higher, ’cause if you don’t remember, and I may talk about this on the next slide, in fact, lemme just see if I do. So her TPO antibodies were not high, kind of middle of the range. Probably doesn’t have Hashimoto’s, but maybe. So yeah, so let’s break these down. So, T3 uptake has nothing to do with actual T3 levels. It is an inverse indicator of thyroxin binding globulins, which are transport proteins, okay? So, don’t confuse this with thyroglobulin, because that exists inside the thyroid gland. I know they sound similar, and the abbreviations are similar. So TBG, which is what that is, that is like a taxi cab that the hormones have to get in to be transported around the body, okay? Now, here’s the thing. If your T3 uptake is low, that means your thyroxin binding globulin, or the taxi cab, are high, okay? Now, her T3 uptake is really low. 20% is really low, which means she’s got a lot of taxi cabs. Now, I will tell you that there’s a couple of things that will make your thyroxin binding globulins elevate. You know what they are, Freddy? – I do not. – Well, the biggest thing that’ll do it is estrogen. So, estrogen or excessive estrogen or exposure to estrogen will elevate your binding globulin levels. It’s just a totally known fact that’ll happen. Inability, and thus, here’s where my little clinical experience comes in, in my opinion, inability to eliminate estrogens will cause those estrogen levels to increase and thus your binding globulins to elevate. So I can tell you, when I see a T3 uptake of 20, I go, wait a minute, there’s something going on with estrogen levels or estrogen elimination via the liver, okay? But that T4 and T3 level up there, that doesn’t make any sense. The reverse T3 being high, here, since the free T3 isn’t high, and low, it’s probably just a cytokine load, causing her reverse T3 to look like that. That’s all that means, okay? So what do you make of that? Well, it’s hard to understand what’s going on, but I’m gonna tell you what I make of it. There is probably assay interference going on. Like, she’s taking something that is interfering with the labs’ ability to accurately assess her hormones. We call that assay interference. So guess what we’re gonna do? We’re gonna rerun that test, because I need to see, if we run this again and that exact same pattern shows up, I’m just gonna say the problem is most likely Hashimoto’s, ’cause Hashimoto’s is the only thing I can think of that would make some levels high and other levels not. Perhaps there’s some other kind of weird thing I don’t know about, but we’re gonna rerun those, and don’t be afraid to do that. Don’t be afraid to cal the lab and say, these results are really weird. Do you guys know what would cause this, and sometimes they’ll say, oh, yeah, here’s what could cause that. Just so happens that in this particular case, we’re gonna retest the thyroid panel. Now, at the time that we got her blood results back, we were still waiting on her DUTCH panel. Because of cycle timing, you have to collect that at a certain time of the month. You can’t just do it whenever you want, especially in a cycling female. – Mmhmm. – And lemme just stop there. The thing that can interfere, ’cause I don’t know if I have a slide on it, the thing that for sure can interfere with thyroid testing is biotin, and it just so happens, after I quizzed her some more, she didn’t tell me she had been taking a big ol’ amount of biotin. She didn’t put it on her intake form, and biotin, in large amounts, can interfere with several different of those markers, how they assay it in the lab, and there’s some good papers on that. And so, that’s the first thing I thought, is I wonder if she’s taking a lot of biotin she didn’t tell me about, and she was. So, okay, we’re gonna stop taking the biotin, and we’re gonna recheck this in a couple of weeks, right? Still waiting on the DUTCH panel. Now, she and her mom really wanted me to do something for her, right? They really didn’t wanna wait until I got the DUTCH panel. So I went ahead and put her on some adrenal cortex/glucose utilization support, and it’s a formula I use a lot for people that I think have tissue hypoglycemic or have that adrenal hypofunction. I use an adaptogen formula, and I’m not giving you the names ’cause it doesn’t really matter. We can give you the name some other time. I’ll talk about it in the seminar some, but just understand the concept, right? We think she’s got an adrenal problem. Let’s do something for that, right? And so I kind of go at it from two ways. I go at it from giving the gland what it needs to actually make cortisol, and then the glucose utilization, there’s certain minerals like chromium and vanadium that help with transporting glucose into tissues, right? You just don’t use ’em at the same dose as you would with someone who’s insulin resistant, okay? The adaptogens, if you guys don’t know what those are, adaptogens are plants that have adaptogenic function, meaning if the HPA axis is running a little bit low, weirdly enough, adaptogens can shift ’em back to normal, and if the HPA axis is running a little high, adaptogens can shift ’em back to normal. They do that through the hypothalamus and via cytokine modulation. That is how they do it. They don’t really directly, the active constituents in adaptogens don’t really do anything to the adrenal gland. They do it to the command system that is sending signals to the adrenal gland. And we’ll talk about that. Adrenal stuff, we’ll talk about that a lot in the seminar in December. I put her on a pretty healthy dose of EPA from fish oil because it’s anti-inflammatory. I let her continue taking liquid turmeric and liquid resveratrol ’cause it’s anti-inflammatory. I’m kinda hedging my bet on that a little bit, you know, kind of saying, well, she’s got some inflammation. Those are pretty much the best things I can do for it, and that EPA, by the way, is not only good for inflammatory support; it’s also important for receptor function. Receptors in phospholipid membranes in the body, if you don’t have the right fatty acid composition, they don’t work. So fatty acids are very, very important. I’d use topical glutathione. Again, I’m kind of taking a little hedge against an inflammatory autoimmune problem, and I decided to go ahead and give her some intestinal barrier support. So what I did basically is I kind of said, this is kind of a placeholder treatment plan, until I get those DUTCH results back, right? And of course she was already on a gluten-free diet, dairy-free with lower FODMAPs foods. Now, here’s the results for the thyroid. Now, the TSH, still normal, down a little bit, no big deal. The T4, still high, but down. The T3, that’s still kinda funky high. The T3 uptake is still lab low, but not quite as low as it had been, and the reverse T3 is now normal. So it dropped 10 points. So her free T4 is still okay. Her free T3 is a little bit lower, no big deal. Her TPO antibodies went up a couple of ticks. So I still think this is probably assay interference. I think that she was taking a lot of biotin, and I think it has not cleared her system, and so the results look a little bit different, but not completely. I mean, they’re still pretty abnormal. This is still an issue, this T3 uptake. This still makes me suspicious that we’ve got excessive estrogen going on. So, what would do that? Assay interference, and possibly Hashimoto’s, but it’s more likely assay interference. So, so before we get these DUTCH results back and we look at ’em, so, when you’re looking at hormone quantities, so you can’t look at receptors directly, right? So with any type of hormone situation, whether it’s thyroid hormone or estrogen or progesterone or whatever it is, there is no way to directly lab test what the receptors are dealing with. We just don’t have the capability of doing that. So, we’re always having to look at downstream, look at enzyme function, look at hormone quantities, and then look at their symptoms. Symptoms are very, very important. We should never discount what the patient is telling us about how they feel, especially if we know how to interpret what their symptoms mean. So, with hormones, we’re looking at quantities, but we’re just gonna have to make some assumptions about what the person’s actually doing with those hormones. So I’ll tell you what I mean in just a sec. So, this is just a general concept. I’m not gonna go through all this, but all these places that you see, you can have a problem with any of those. You can have a problem with the hypothalamus, pituitary, with making the hormone, with transporting the hormone, with converting the hormone, with eliminating the hormone. Hormones have half-lives. They’re not supposed to hang around forever, and you will see problems if the liver does not excrete these, okay? If hormones are not excreted, and they’re primarily excreted through the feces, you’re gonna have problems, because what happens is those hormones become available to go back into circulation. This is a problem, if you have one there. You can have a problem with receptor binding, with proteomic responses. You can have a problem with feedback. These are all places you can have problems, and if we had time, I would go through each one of these with you, but at the seminar in December, we’re going through all of that, so you can understand where the problem, where in a patient the breakdown could be so you don’t get lost. All right, here’s all these animations, okay, great. You guys understand that. Now, here’s her DUTCH results. Let’s just start here at the estrogens. So, her total estrogen, that little purple thing is in the post-menopausal range, okay? Her progesterone is definitely below where it oughta be, and it’s almost in the post-menopausal range. Her testosterone is actually above where it’s supposed to be. Now, that’s just a quick little glance at it. Now, you may be thinking to yourself, I don’t understand why that looks like that, all right? I don’t understand why that looks like that. – That is correct. – Now, if you look here, DHEA production index is high. I mean, that’s pretty much double what the reference range is. She’s at 6,000, and 3,000 is where it kind of tops out as being okay. Her free cortisol looks high. Oh my God, it’s high cortisol, that’s the problem, except her metabolized cortisol is actually low. Now, when you see metabolized cortisol low and free cortisol high, there is something going on between your thyroid and adrenal glands, okay? There’s something going on there. One of those is a problem. It’s either the adrenal glands are a problem, or it’s the thyroid gland that’s the problem or both. Now, you may not be able to dig deep into that right now, but just trust me, that’s what’s going on. Now, lemme just show you in a slightly different way. So this is just kind of a table view. So, look, her pregnenolone, her progesterone metabolites are below pre-menopausal range, by a lot. All of her androgens are above range. Her estrogens, E1, E2, and E3, are below pre-menopausal range. What do you think about that? – Couldn’t tell you. – Well, it’s exactly what you would see for someone taking birth control pills. – Oh, interesting. – Because she’s not ovulating, and if she’s not ovulating, you’re not gonna see estrogens. This is exactly, those low progesterone and low estrogen is exactly what you would see if she’s taking birth control, which she is. What’s not normal is this stuff. These androgens being high, that is not normal. That is not normal, and so that, we’re gonna have to dig a little deeper. Now, I knew that her estrogen and progesterone were gonna be low because of the birth control she was taking, but we still wanna run it and see, are they doing what we expect them to do, right? Well, those androgens being high is totally not expected. Those are really high. So let’s go a little bit further here. Now, with these cortisol results, I’m gonna skip over these a little bit, but just show you that looking at cortisol and cortisone is more valuable than just looking at free cortisol, okay? Just trust me on this for now. It’s more valuable than that, because this person has a metabolized cortisol, which is really your best index for overall production, is low. So, as I was telling you a second ago, there’s something going on with her adrenal glands and/or her thyroid gland. We already saw those thyroid numbers were really weird. Those were really, really strange, so strange, I don’t really know what’s doing it, unless it’s assay interference from biotin. All right, now these are some steroid pathways, and what I’m just gonna show you guys is how we start to utilize knowledge about enzymes in working up a case. Some of this may just be totally word salad for you, but just kinda get the concept. So, there’s her results. – Mmhmm. – So if her DHEA is above range, let’s just start up here. It’s up here, right? So, if that’s already high, that means that her pregnenolone must be getting shunted over here a lot. So this enzyme right here must be pretty active. Now, androsterone, etiocholanolone, testosterone, let’s look at these guys down here. All right, so what I’ve highlighted is these different enzymes that are involved in this patient’s results. Now, her DHEA is high, and so we would expect some of the downstream things to be high as well. It just so happens that right here in this pathway, this enzyme and this enzyme, 17-beta hydroxysteroid dehydrogenase, are the same enzyme, and look here, androstenedione and testosterone, 3-beta-hydroxysteroid dehydrogenase. So, it could be that what’s going on with her is that she’s got an upregulation of those two enzymes. Now, granted, her DHEA is already high. So it could be that what she’s having is just increased production of DHEA. Now, lemme just tell you, what is the name of the, I’ll ask you, what’s the name of the condition where a woman has increased androgens? – Does it begin with an H? – No, it’s called, well, that’s hirsutism. Polycystic ovarian syndrome is what with we’re talking about. – Oh, PCOS? – Yeah, so the first thing I’m thinking is, wait a minute, you know, she might actually have PCOS, right, which is a condition we’re gonna talk a bunch about in December. And so, what I’m gonna do is I’m going to send her out for an ultrasound and find out if she’s got cystic ovaries or not. – Mmhmm. – Now, here comes the stuff that may be a little hard to understand. In the guy, okay, there are some bacteria, there’s a lot of different kinds that can do this. They can make an enzyme called beta glucoronidase, and this is very important, because hormones are detoxified and biotransformed largely through glucuronidation, which is part of your liver biotransformation pathways. What can happen is you can have hormones be put into the GI tract, and then if you’ve got an overgrowth of bacteria that produce beta glucuronidase, what they do is they cleave that glucuronic acid off the hormone, and the hormone is now free again and can get reabsorbed through enteric and hepatic circulation, and now, you can have hormone overload. You follow me on that? – Yeah. – That’s something that can happen. It’s for sure something that can happen. Now, what happens, as I just said, it deconjugates hormones and puts ’em back into play. So, that can not only happen with beta glucuronidase; this can occur with hydroxysteroid dehydrogenase. You can have bacteria that essentially put those hormones back into play, okay? Now, that can happen with Beta HSD-3 and 17. Now, there is a substance, I’m gonna just kinda give it to you now. There’s a substance called calcium D glucarate, which inhibits the beta glucuronidase, okay? And if you do a little reading, you’ll see where some people use calcium D glucarate to do hormone detoxification to improve hormone elimination, to improve liver function. Well, I use it for that as well. So in this case, we got a patient who’s got really high androgens, and that’s weird. She shouldn’t have high androgen, and it just so happens that the enzymes involved in those are hydroxysteroid dehydrogenase enzyme, and it could be that what’s happening is is as, it could be that she has a DI dysbiosis of some kind, I know I’m kinda getting to left field here, that is causing her to resupply or recirculate these hormones. Now, that can also happen, that whole gut thing that I’m talking about, that same thing can happen if your liver isn’t working very well. So, hormones have to be eliminated, right, and they’re eliminated through phase one and phase two detoxification, but if your liver velocity slows down, then just like a sewer system, those hormones back up, and they can recirculate and exert their effects all over again. That is something that I clinically know can happen. I’ll be totally honest with you. I haven’t found any research to support that, but I can tell you just from clinical experience, that has to be what’s happening in some people, because when we treat their liver or give them liver support, sometimes their hormone, actually, not sometimes. Very often, those hormone symptoms go away. And even objectively, high hormone levels go away, so that’s gotta be what’s happening in some people. So knowing that I already know that, with this patient, I’m thinking, well, that might be what’s going on with her. So what we did is we tried some anti-inflammatory stuff. That didn’t help. Tried some adrenal/blood sugar support. That really didn’t help. The hormones are abnormal, and I don’t know for sure if that HSD thing is going on with her gut, but I gave it a shot, because it’s worked before. So here’s what happened. In late September of last year, she stopped that protocol with the turmeric and the resveratrol and the adrenal stuff, ’cause it wasn’t really helping, it wasn’t doing anything. So call a spade a spade. There is no shame in saying, well, that didn’t work. You gotta know what’s next though, right? – Sure. – That didn’t work. Okay, great, what’s next? What do we do? Do we give up, do some more tests? Tests for what? So, in early October, she started that broad liver support, which was to improve phase one and phase two elimination, to improve how fast her liver was working. Now, that’s just a guess on my part, guys. It’s just clinical judgment from experience. That’s one of the things I’m gonna be sharing with you, is I’ve got some things that I can for sure give you all kinds of references for, and then there’s some stuff that I don’t have references for. I can just tell you that it’s worked, and here’s probably why it’s worked, but I don’t have research to back that up. That’s still valid, in my opinion. But, when she starts the broad liver support, it makes her headaches worse. Well, crap. So late October, she stops her birth control pills. She kept asking me whether she should stop it, you know, and just because of some liability reasons, I was like, I can’t really tell you to stop it, but I think if you wanna stop it, that would probably be okay, because birth control pills have a real interesting effect on some people. They tend to consume methyl donors, because methyl donors, methylation in the liver through COMT is one of the ways that your body eliminates hormones, and for some people, taking birth control pills overwhelms those methylation pathways, and they get high hormone symptoms, all right? So she stopped the birth control pills in late October. Early November, she starts calcium D glucarate, ’cause look, I gave her this broad liver stuff. That was too much, didn’t work. So I said, you know what, let’s go down lower. Let’s just try calcium D glucarate. And as you can see, once she’s using that for a week or two, the morning headaches are gone. – Interesting. – They’re gone. So I said, okay, this has gotta be part of what’s, this is scientific observation, right? This has got to be part of what’s going on, these hormone elimination pathways, gotta be. In December, we recheck her thyroid panel, because it had been abnormal those couple times. In December, it’s totally normal, right? So either we did something that helped that, or it was assay interference, like I said earlier, and it just took a long time to get all that biotin out of her system so it wasn’t interfering with the thyroid test. I don’t know which one it was. I mean, I really don’t know. But at least we know her thyroid, we don’t have to worry about that, right? Thyroid’s not the issue, and her morning headaches are gone using the calcium D glucarate. That is all good stuff for us. Now in January, she starts a diet, where Monday, Tuesday, she’s having grain, fruit, protein, and fruit. Wednesday, Thursday of the diet, she’s doing protein in veggies, and then Friday, Saturday, Sunday, she’s adding in fats to those things. Now, she’s having no alcohol and no caffeine with that diet, and just so you know, that diet would help increase her microbial diversity. ‘Cause I’m still holding on in my mind to this thing about, maybe she does have a GI dysbiosis, and she’s having that beta glucuronidase/hydroxysteroid dehydrogenase thing happening, and that diet right there would increase her microbial diversity. You know, maybe this helped, I don’t know. February, March, this is a year and a half ago, February and March, she’s taking nothing, no supplements. April, she feels normal, no headaches. Now, the further away she got from stopping the birth control, birth control pills, the more her symptoms lessened and lessened, until about five months off birth control and taking no supplements, she had no headaches. So what do you think? – I mean, it seems like birth control was obviously doing something for her. – Yeah, I mean, do we know definitively exactly why and how? No. All I know is the birth control pills, for some people, they don’t react well. It does not react well, and in her, it was causing some kind of dysautonomia, right? There was a lot of different things we could posit about why it did what it did, but in terms of treating her, what we found out is that when we tried some of the things, it didn’t work, so we stopped doing ’em. We tried something else. And we used the test data to give us a clue about what’s going on. Those androgens being high and those couple of enzymes being involved starts making us think, there’s something going on with hormone elimination, maybe, right? And then when we looked at her blood work, that T3 uptake was low. That already told you there’s something going on with estrogens, and in my opinion, just a little nugget I’m gonna give you guys, if you see a T3 uptake that low, your first thought oughta be, where is this estrogen coming from, or why can’t this person get rid of it? Either she’s taking it or she’s taking it and can’t get rid of it, or she just can’t get rid of it, which is why, from my previous experience, I wanted to try some liver support. Liver support didn’t work, and she had a bad reaction, for some reason. I don’t know why, right? And when I’m talking about broad liver support, there was like methyl donors were in there, milk thistle, all the kinds of standard stuff you guys would use. Didn’t work, it made her worse. So we had to stop it. So I thought, well, I’m not gonna abandon that completely. Calcium D glucarate is something that can improve elimination of hormones, and it can do it through a couple different mechanisms. She started to do well with that, and then, she started to do so well that we just said, hey, stop taking it, and then the farther she got off of the birth control, no more headaches. So, I have to come to the conclusion that it was the birth control pills that was probably the factor, maybe other things going on as well, but probably the main thing that was causing her to not be able to get rid of the headaches. It’s like, sometimes you just gotta figure out what it is and get rid of it, right? – What this makes you realize is like, you have to know so many various things about the woman’s cycle, and are the hormones clearing. There’s just a lot of data points you gotta know about, let alone what they’re taking for birth control, what type of effect it’s gonna have. Are you gonna be breaking down the different types of birth controls and the effects they have in the December event? – Yep, and that’s the exact point I was gonna make, what you just said, is you gotta know a lotta stuff. I mean, you really do have to know a lot of stuff, but that’s okay. If you’re looking for a cookie cutter thing, go someplace else, I suppose, ’cause I mean, you could have given her, I mean, you could chase that stuff that she had forever. I’m not saying I did the best job. I did the best job I could at the time, and next time something like it shows up, I should do a better job. But you really do. You’ve gotta know all this different physiology in order to know what should even be on your radar, right? And sometimes experience comes with that, but that’s one of the advantages of taking a seminar, because I’m gonna share with you my experience. I’m gonna kind of speed up your clinical progress when it comes to these kind of cases. And yeah, we’re gonna have to go through those different kind of birth control pills, and just realize now that most of them work be inhibiting ovulation. That’s how most of those guys work, and a lot of people don’t do well with them, because it overwhelms their ability to biotransform and get rid of ’em, and it consumes a lot of their methyl donors, ’cause that’s primarily how you get rid of most of this, through methylation, and as well with glucuronidation. So, the takeaways are, you gotta know your stuff. Do testing that makes sense for that case. Use four priorities to prioritize your treatment. So what did we do with her, right? We said, okay, does she have an autoimmune problem? Eh, you know, not real clear, but you know what, we tried some anti-inflammatory treatment and it didn’t help, so she probably doesn’t have a real significant autoimmune problem. We still answered the question, but we answered the question with treatment, as my other students will know from the other classes we’ve done, right? Did she have a red blood cell problem? No. Did she have a blood sugar/adrenal problem? Well, it kind of looked like it, but when we treated her for it, it didn’t help. And she may still actually have an adrenal gland problem. It’s just not related to her headaches, right? And did she have any GI or liver? Well, liver problem, not really, necessarily. Like, there’s not a way to really assess that. Her liver enzymes weren’t elevated, but most of the time, they aren’t in these people that I’m talking about that need to have liver support. Most of them, they’re not elevated. So, we had to just go with what made sense. We checked her hormones. That put us on the lookout for what’s going on with her GI and her elimination, and then we just did some stuff and see if it was gonna work. But if it didn’t work, I knew what was next. So the thing is, you’ve always gotta know, what’s next? And the way you know what’s next is knowing your physiology. So if you look at that lady’s thyroid panel, and now, if you ever see something that’s totally, like, if you’ve taken my thyroid class and you’re like, man, those results don’t match up, those don’t make any sense, you think to yourself, maybe it’s assay interference, and if you’re kind of lost, call the lab up and say, hey, do you think this could be assay interference? They’ll go, I don’t know, let’s check it. A lot of times, they’ll just rerun it for you at no cost, because they want good quality control. So yeah, you’ve always gotta know what’s next. And what’s next is this slide. You need to know which nutrients and herbs and supplements cause the desired changes in physiology. You gotta know that stuff, and you integrate brain-based treatment when appropriate and indicated, but she’d already had it. She’d already gotten what she was gonna get out of that, and it didn’t get rid of her headaches. But this was able to do that, so I’m very fortunate and feel lucky that we were able to make that happen. So, you guys probably won’t see all the technical difficulties that we had during this. My computer was being very strange. There may be a lot of cuts that Freddy has to make in here to make it look pretty, but my computer just was not cooperating. So, what are we gonna do in this class? Well, in December, the class we keep alluding to is the Mastery of Neurochemistry of Male and Female Hormones, and Freddy will say a couple things about this in a second. But I’m just gonna tell you that you’re gonna have one heck of a flipped classroom. I’m gonna give you a bunch of stuff. We’re gonna go through all the physiology that’s relevant to male and female hormone problems. Now, what I wanna mention is we’re gonna kind of lean more heavily on the brain sort of aspects of this. So yeah, I could give you a whole class on how to treat infertility, but that’s not really what I’m gonna get into, and that’s just a little bit outside the scope of what I think we need to do. So we’ll be talking about female hormone problems like endometriosis and PCOS, but what do they mean to you clinically, right? Does it have an effect on their brain function? What kind of symptoms do they cause beyond just gynecological, hormonal problems? We’re talking obviously about male hormone problems, like low T, and does someone really have low T, and how do you find out, and obviously, androgens and estrogens play big roles in neurodegenerative prevention. So those are all the kinds of things we’re gonna be talking about. But I’m also gonna be hitting adrenal physiology, because just as a little preview, adrenal physiology is really important when you’re talking about female hormones, especially when they hit menopause. The adrenal glands become really, really important to understand. So, those are just a little sampling of the things we’ll be talking about, but all of it is gonna be actionable, right? It’s all gonna be applicable, meaning I’m not just gonna say, hey, this is a problem. We’re gonna go through cases and make sure you understand and make sure you grapple with the information so that when you leave the seminar, you actually know what to do, and of course as Freddy will tell you, you’re gonna get one year of on-demand access that you can go back and watch parts over and over again, so you’re not gonna miss anything. The way they’ve got it set up, guys, is, I mean, they’re not charging you anything extra for that. They could, and it’d be worth it, but they’re not doing that. So, when you have online, on-demand access, you don’t miss anything, right? You can be in the class, take notes if you want. You can absorb, but you’re not gonna miss anything, which I think is super valuable. I wish they’d had that 10, 15 years ago when I was still taking a lot of classes. What’d I miss? – No, you did great, and what you’re saying in regards to making the education actionable I think is one of the reasons that you have such a large following here at the Carrick Institute and why you’ve been a PBS Educator of the Year as well. We keep hearing again that you’ve given things to do right away with the material, and you break down complex topics, and this one, to me, you know, like I said, I have a masters in nutrition, but the hormone stuff has always got me, especially when it comes to female hormones. So I’m excited to attend the class and hear from you and make that complicated information digestible and then teach me what to do from it, and you covered everything else great. The class is in December, and I think it’s one of the last few opportunities to attend via livestream. – It is the last one. – If that is something that you need to do for your neurology hours, so you get to learn some neurology, some neuroscience, and some neurochemistry and hormones. So it’s a pretty good one. You probably don’t wanna miss it. – ‘Cause we’re talking about the brain, by the way. I want you guys to know that. We will be talking about the brain’s influence on this stuff and how these things influence the brain. It’s not gonna be a class just on how you make a woman have a period again, right? I mean, yeah, that’s cool, but we really have to kind of keep it focused more on like, if someone comes to you with headaches, what are you gonna do? Well, you’re gonna know. Once you take the class, you’re gonna be able to go through and say, well, if she has PCOS and headaches, that puts me over here, right? If she has headaches and she has no period, that puts me over here. So we’re gonna integrate that into looking at it still from many primarily neurological symptom, neurological presentation model. But anyway, I just wanted to make sure we were clear on that. But we’re talking about the brain, for sure. – Yeah. So this class should really only matter to you if your patients have brains. – Yeah, if they have brains and sex organs, this should matter. – Yeah. We’ve got it covered in one class, right? Dr. Clark, thank you very much for taking time out of your busy day to do the case review. I know the students around the world who tune in to these love ’em, and then, we’ll see you down in December, and we can’t wait to have you. – All right, see y’all, have a good one.
Welcome to episode #3 of CI TV! In this episode, Dr. Clark walks you through his clinical thinking process of a 20-year-old female who is suffering from headaches. Female hormones are the focus on this particular case review. Would you have come to the same conclusion? Watch below to find out!