Thyroid: Beyond TSH - The Markers That Actually Predict How You Feel

All right, everyone. Welcome back to Cell To Systems. Episode 16 is all about the thyroid. And holy smokes, I didn't know this, but apparently 5% of all Americans have some sort of thyroid disease. Today, we're going to dig into it and get all the details. So, Craig, you brought this topic up. You wanted to talk about it. Let's go.

Yeah, this is going to be a great topic for today. You know, thyroid is something that we really are addressing regularly inside longevity practices. And we're usually addressing it in somewhat different fashion or substantially different fashion than what patients are accustomed to within their traditional primary care model. A lot of people in the population are dealing with some component of thyroid dysfunction, whether that's, you know, a sluggish thyroid to a thyroid that's hypo-functioning, or whether there's some excess of thyroid hormone that's contributing to a whole other symptomatology. I think we're going to get into all of that today.

What I wanted to first start out by saying is that the thyroid is really driving a lot of metabolic activity in the body—that's its major role, and so it's extremely important. It's an extremely important organ, and I want to provide a little bit of a basis for how thyroid signaling works in the body, the mechanisms and so forth, before we get into it. We're going to be throwing out a lot of terms today like TSH, T4, T3, maybe talking about antibodies, things of that nature, and it's very important to sort of understand the relationship between these different terms and how they work.

So to give a rundown, it all kind of starts with the hypothalamus. The hypothalamus is going to release a hormone called TRH. That's thyrotropin-releasing hormone. This hormone communicates to the pituitary gland, and in response to that, there's a release of a hormone called TSH, or thyroid-stimulating hormone.

Now, once TSH is released and circulating in the bloodstream, what happens is the thyroid gland takes iodine from the bloodstream and combines it with an amino acid called tyrosine. Within the thyroid gland, after this combination occurs, essentially we have the production of what inevitably becomes our thyroid hormones. The major production of thyroid hormone is in the form of T4, or thyroxine, within the thyroid gland, and to a lesser extent—substantially lesser extent—triiodothyronine, which is T3.

Now T4 is then converted into T3 in the thyroid, but also peripherally in the brain, skeletal muscle, the liver, and the gastrointestinal tract. T3 is the molecule that enters the cell that really sort of exerts the beneficial effects of thyroid hormone at the tissue level.

The last point I want to make about this before I sort of kick it off to my colleagues here is that when we think about TSH and the labs that you get monitored when you go to your practitioner, a lot of times we're checking a TSH sort of as the baseline, fundamental "hey, what's going on with the thyroid?" There's an inverse relationship with TSH and our thyroid hormone, such that if thyroid hormone is low, or the activity of the thyroid hormone is being blocked, we're going to have this paradoxical increase in TSH. All right? And that's very important to understand.

So TSH often climbs with a hypo-functioning thyroid gland. It can climb for other reasons and contribute to a hyper-functioning thyroid; that's a whole other story. I don't know if we're going to get into that today. So, it's very important that we understand the relationship. As T3 levels rise, thyroid hormone levels rise, we're going to see a decrease in TSH. As T3 and thyroid hormone levels decrease, we're going to see that compensatory increase in TSH.

Within longevity practices and cellular medicine practices, you know, we pride ourselves because we're looking at thyroid at a much deeper level usually than your average primary care. We're looking at the TSH primarily initially as a fundamental evaluation, but we're also looking at free T4. We're looking at free T3. We're looking at reverse T3. Okay, there are three enzymes—deiodinase enzymes—that are responsible for converting T4 into T3 or into a substance called reverse T3, which is potentially problematic but has a purpose in the body as well. So, anyway, we're going to dive into that today. I just wanted to provide some basis for what's happening in the thyroid and the signaling and the feedback loop. I will either give it back to you, Jock, or punt it to any number of our colleagues who want to. Yeah, go ahead.

So, you talked about a lot of different biomarkers, but most people probably listening to this only know a TSH level. Is that the standard? Are most people going into their medical practitioner's office and they're getting just the TSH level? What are they missing when they just see that level?

Yeah, great question. Very important. So, TSH is commonplace, and it's going to be assessed pretty much across the board when somebody's looking at thyroid. What's being missed is that TSH is going to stimulate thyroid hormone production, and when we're evaluating thyroid hormones, we really need to look at free T4. That's bioavailable T4. And free T3, which is produced from a conversion that happens from T4. We also need to look at that reverse T3 level.

A lot of times, practitioners in the standard industry are looking at TSH and they're looking at a T4 level; they may not be looking at the free value, but they're oftentimes not looking at a free T3, which is critical. That, again, is the hormone that we really need to get into the cell to exert the benefit. There are any number of things that can impede that conversion of T4 into T3: chronic stress, inflammatory signaling, stress that's related to caloric malnutrition and caloric deficiency, and micronutrient deficiencies. So that's where I want to sort of hand it off to you guys and say, what are you seeing most often in your practices? I know that personally in my practice, I'm regularly seeing people that have micronutrient deficiencies.

They have inflammatory or chronic stress signaling that's really sort of impeding that conversion of T4 into T3, and this is contributing to a lot of hypothyroid symptoms—namely fatigue, brain fog, constipation, cold or temperature intolerance, changes in their blood pressure, changes in their lipid profile, having brittle hair and nails, and things of that nature. So, that's where the workup really begins. What are you guys seeing?

I think this is where it gets kind of confusing because you named so many things anywhere from like cholesterol to brain fog. It almost feels like or sounds like it touches everything, right? I think that's why maybe it could be overemphasized, just because any symptom you can relate to the thyroid hormone. But my question for anybody is, why is it that the standard is just a TSH level? Like, what's the controversy? Is it a price thing? Are these other biomarkers expensive? Is there not enough literature on it yet? Like, why is it that a traditional doctor is only running a TSH level and not these other ones?

Well, I mean, my opinion of it is the TSH—I mean, that's levothyroxine as far as big pharma, that's being regulated with it. And it's, you know, sadly, that's what a lot of patients, if they're coming in with outside labs, they never have the complete thyroid panel that we need to really assess it.

How I kind of describe it is like your thyroid hormone acts like the ignition key for your metabolism. Just like Craig was saying, it helps to help regulate mitochondria function, energy production, body temperature, cognitive performance, and kind of like where my area of interest and passion is: the gut health and the cardiovascular benefits of having an optimal T3 activation going on.

I think, sadly, there's just not a lot—it's overlooked between thyroid health and female hormone health. I mean, so often women will come in thinking they have an estrogen or progesterone issue, but in reality, it's an underlying thyroid issue that's contributing to their symptoms. I mean, the thyroid and female hormones are so deeply interconnected. If the thyroid function is suboptimal, many women will experience anything from younger, irregular periods, worsening PMS symptoms, heavy periods, low progesterone, and then the estrogen dominance, and then fatigue. So many women that come in are already on hormones, or we've started them on testosterone or progesterone somewhat, but then they still remain fatigued despite being on hormone replacement therapy. It's almost always a thyroid that's been missed.

And then like I said, another critical connection is the gut health. In fact, much of the conversion of T4 into active T3 occurs through processes influenced by gut health. So if someone has chronic inflammation, gut dysbiosis, food sensitivities, or poor digestion, likely thyroid hormone activation is going to be suffering, which is going to also lead to decreased gut motility. Then this creates the vicious cycle, with poor thyroid function contributing to the constipation, the bloating, and then the bacterial overgrowth. It blows my mind how much bacteria that we as providers sometimes overlook because of the overgrowth of the bacteria because the thyroid is just not functioning right.

And then, you know, like I said with the heart health, just like Craig was mentioning, I mean, we've all seen it. These women that are post-menopausal, or even pre, that all of a sudden start developing some A-fib. I mean, it's a thyroid-related issue that's just suboptimal, and then their cholesterol starts increasing. But then, where I get excited about it is it's a pretty easy fix. I mean, once you just do a deeper dive and you start addressing it, all of a sudden their gut is starting to improve and then their cholesterol panels are improving.

Yep. Yeah. And one of the things that was so wonderfully said, Christy, and I think it's really important to sort of just reiterate that all of these things, as Christy mentioned, it's a cycle. It's a vicious cycle. So when you start to slow down metabolism, you're starting to slow down peristalsis and gastrointestinal motility. For example, you're contributing to changes in the way that estrogens are eliminated from the body and how they're getting reabsorbed, contributing to an estrogen-dominant pattern.

Well, estrogen dominance is one of the main drivers of like thyroid dysfunction, or it can be a primary driver. I don't want to say it's one of the main ones, but all of these things signal in ways that feed back to each other. It's a loop. Everything is related. And so, the reason I emphasize that is because, as Leonard was mentioning, you have to work with a provider that's going to make the connections between all these body systems.

When you're leaving out key biomarkers, when you're leaving out and not considering the connections between thyroid hormone and adrenal hormones, thyroid hormones and sex hormones, thyroid hormones and cardiovascular risk, thyroid hormones and brain health risk—all these things—you're really just not fitting the pieces of the puzzle together in any meaningful way that's going to benefit the patient. So working with a longevity medicine practice, working with a cellular health provider, is really the best avenue for patients to go down to comprehensively evaluate the picture in its entirety, and thyroid certainly plays a big role in that.

So I have a question, Dr. Free. When you have a patient come in, how frequently are you testing thyroid right out of the gate?

Almost every single patient. And I think this was a great question, Leonard, that you asked a minute ago. When Jock said it was 5% of the population, I was like, I don't think it's 5%. I think it's like 50%. But that's because I'm testing every single patient, right? And I'm doing more than just a TSH on all my patients.

So, we have to remember we're sort of selection-biased because of the practice that we have. For the majority of basic primary care doctors, a TSH is probably adequate; the additional labs don't add any more than what they would have, and TSH is awesome as a screening tool, but it's not the end-all, be-all once we begin. If I'm treating someone who comes in with fatigue—which is probably my, I would guess, my number one sort of reported symptom besides the biohackers who are trying to optimize their lives—for the sick patients, the majority of them, fatigue is their number one symptom, and so thyroid is part of that panel that I'm looking at.

Because they're reporting a symptom, this isn't just somebody coming in for their annual physical. This is somebody who's coming in either because "I want to know exactly how all my organs are functioning" or "I want to know what the reason for my fatigue is." I'm going to do that deeper dive. So, we have to remember that we are a little bit selection-biased based on the patients that we see.

We also are a little bit selection-biased because the patients, even the biohackers that we're seeing, the high achievers that we're seeing, these guys also are running their hormones out. We're seeing these perimenopausal patients that are running their thyroids, and so they're more likely to have more complex thyroid disease in the first place when we're seeing a normal TSH, which is what we're talking about here.

What is normal for a TSH? For me, I say it's between one and two. That's kind of average, right? Between one and two. I certainly let people go above or below that depending on what else I see in their entire panel. So, I'm going to go then look at their free T3 and free T4, which are, as Craig said, their active hormones. I'm going to say, okay, these should be within a normal range. A free T4 greater than one, somewhere in that range. A free T3 somewhere greater than three; somewhere between three and four and a half is probably a good range to go.

The confounding factor that happens that makes this whole thing weird is what you were trying to talk about earlier, Craig. When the thyroid, the TSH—thyroid-stimulating hormone which stimulates the thyroid—comes back normal, but the free T4 is normal and the reverse T3 is high. That's where we see a lot of our patients. I think that what we're all talking about here is this like higher reverse T3.

So this means that instead of—I'm drawing the picture that I usually draw for my patients in the air [laughter]—that instead of the T4 that gets produced by the thyroid gland, instead of that going to make this active, metabolically functioning hormone that does all the things—the hair, the nails, the skin, the bowel movements, all of those things to make those things function—it instead goes over to this reverse T3, which also binds to receptors on cells but it blocks that active thyroid hormone from binding. So now none of the things you think are going to happen with thyroid hormone actually happen inside the cell.

Reverse T3 for me is really a marker of metabolic function, of mitochondrial function, of cellular stress like oxidative stress. So I use reverse T3 as a "what else is happening inside the cell?" I use it in conjunction with things like OxLDL, like 8-OHdg. I'm looking for how damaged or diseased is this cell or this system, and how much do I need to pay close attention to it.

Then I'm going to sit with the patient because a lot of the times we have to remember that this is actually a marker—you know me, I'm going to talk about autonomic dysfunction—this is a marker of autonomic dysfunction in many, many, many cases. It's stress of one sort or another, because stress is physical or emotional stress.

When I'm drawing the picture, I put "this is going to make reverse T3 because of whatever stressor is happening." The body doesn't know the difference between this stressor and this stressor. It does the same thing with whatever the stress is. If you haven't read Why Zebras Don't Get Ulcers, great book, and that's great for patients and providers.

What I usually will tell people is if your body—this is where we have to be careful as longevity providers—if your body is making a lot of reverse T3, there's a reason. It's trying to protect you from something. So, the first thing we do, and I do this with my patients, is have them put their hands around their shoulder and go, "Thank you, body. You're doing exactly what I asked you to do. This is awesome." I'm going to start telling you—oh, I'm getting chills—I'm going to start telling you to do something different now. So, let's work in that direction.

Then that's what our job is, is to figure out why they have this different thing happening, like you said. Is it related to too much excessive estrogen? Is it related to stressful situations? They need to start meditating. They need to start doing breathing exercises. Frank, is this related to some sort of overtraining, under-nutrition? You know, we see so many women that are elite athletes that are under-nutritioned, overtraining. And so that's kind of where that goes. I love the idea of remembering that reverse T3 is really a metabolic, mitochondrial, oxidative stress marker.

I have a question on that. That was a great explanation, by the way. Probably the best one I've ever heard on reverse T3. But one of the things that confuses me here is your guys' thought process on how you can identify if that reverse T3 is because really there is truly a thyroid dysfunction, or if it's some outside factor around caloric restriction—especially patients on GLP-1s that are caloric restricting so much—or if they're in like a very stressful environment. How can you tell if, okay, "I'm going to think about this marker right now as thyroid dysfunction" versus "this might be some situational thing that's happening," and then you can kind of overcorrect? Because I think the other side of the spectrum is kind of the controversy with it, where they're saying, "Hey, we might be overprescribing thyroid medications if we're not like thinking about these things." How do you guys make those decisions?

I think that, you know, when I see an elevated reverse T3, my initial reaction is always that this is extrinsic to the thyroid. It's either due to some sort of stress signaling that's happening elsewhere in the body—again, as Dr. Free mentioned, mitochondrial dysfunction, oxidative stress, micronutrient deficiencies. So, I always start looking elsewhere when I see an elevated reverse T3. I'm not thinking, okay, you know, there's some intrinsic thyroid issue happening here, because a lot of times what we see is that the reverse T3 will sort of be elevated in isolation despite, as Doctor mentioned, a normal TSH, a relatively normal T4, and potentially even a normal T3—albeit it could be at the lower third or sort of towards the bottom of the reference range where we would otherwise want it to be optimal. But any other traditional provider—not to throw shade at traditional providers—but they may say, okay, this level of T3 is within the normal reference range, right?

So, anytime I'm seeing a reverse T3—long answer to your question—I'm always looking at those external factors first, trying to correct those. The approach, I mean, if you're really going to like throw—you certainly don't want to throw like more T4 at that and think you're going to fix it. Using a short-acting T3 replacement, you know, you can potentially use that in that scenario to try and break through, as Doctor was mentioning, the blockade on the receptor there. But, you know, that is certainly not my first go-to. I mean, I'm trying to correct the other underlying factors first. A lot of times it comes down to overtraining, under-nutrition, micronutrient deficiency, chronic stress signaling, you know, which encompasses so many different things. We could go on and on about what those are, but yeah.

And that's sometimes a trigger for me to order a nutrient panel, right? Like if I see that they're making plenty of T4, their thyroid is probably functioning fine. It's not a thyroid problem. Now I'm looking at, is this liver? Is it kidneys? Is there a nutrient deficiency? And like you're mentioning about the weight loss medications, obviously, they're taking all kinds of weight loss things. So there's lots of concern there about nutrient deficiency. That's a great place to start.

There are a couple of really great combo things that have just a little bit of iodine, a little bit of zinc, a little selenium, a little magnesium, you know, all the nutrients that typically are required for making thyroid hormone, especially if they're making plenty of T4 but they're not making T3. Sometimes it's related—you know, you always have to think liver and kidney. So, I'm looking at an AST and ALT. I'm trying to make sure those are in the kind of 20 range for women, 25 range for men. That seems kind of low based on your lab values; your lab values are going to be significantly higher than that. But that's based on the research that there should be women around 20 and AST around 20, and men around 25.

If that's not the case, then I'm going to look at liver detox, like I might do a tox panel and see: Is there BPA? Are there herbicides and pesticides? I mean, I can't tell you how much we're seeing of that right now. I think it's because it's summertime and people are outside, and there's a lot of herbicides and pesticides, and traveling a lot. You're getting a ton of exposure to that right now. But you have to watch that; the first place I go is a nutrient panel.

Yeah. Yep. And a lot of times, you know, when people sort of just start throwing things saying, "Hey, I'm going to chase this number by giving a pharmaceutical," we make the problem worse. The next time the patient comes back into the office having done a panel of labs, they say, "Ah, nothing's improved. I've been taking the pill. I've been compliant, taking it every day, avoiding food and calories when I take it," and their numbers look worse, and they feel just as bad or worse. So, you really have to be careful when using pharmaceuticals with thyroid, I think.

And, you know, that's also the timing of when you have the blood drawn. That's really critical. So if they're on thyroid hormone—and we can back up and talk about that too—if they're taking thyroid hormone, this is a whole other conversation because my first thought is not a nutrient panel. My first thought is, are we overtreating them? Right? So then you have to think about having their blood drawn: Are they currently on thyroid hormone? Are they currently on T3 thyroid hormone or anything with T3?

You guys can talk about—I'd love to hear Frank talk about Armour and the stuff you have going on with that right now. But if they have anything with T3 in it, you need to have them fasting first thing in the morning. They can't have taken anything with biotin in it for 3 days prior to the visit. And I usually make them wait 4 hours. I make them take their morning dose, wait four hours fasting, and then get their blood work drawn. So, it's a little bit complicated if they're on T3, and then if they're taking anything with biotin. A lot of hair and nail formulas will have biotin in them.

Yeah. You know, and I remember Frank saying this all the time. You guys are hitting on a couple points where, you know, you're optimizing all these other things. You're improving their metabolic health. They're exercising. And then I know Frank would talk about this all the time, running into situations where he had to make, you know, have phone calls with physicians to de-escalate some of their medications—even things like statins, diabetes medications, and this thyroid medication can be another one. Do you guys run into that situation where as they're getting healthier now, they're potentially having side effects because they're just responding so much better because they have much better cellular response?

Yeah, we just had that happen the other day. I had a gal come in that we've been working really hard on her gut health for other reasons. She had her thyroid removed years ago and we've been working on her gut health, and she came in like panicked and losing her hair. I go, "Let's just check your thyroid." And it was because she had gotten her gut where she was actually absorbing all the thyroid hormone we were giving her. She's down from 150 to 137, which is really a great—I'm super excited about this move. And she's like, "What's happening? Why is this going?" I was like, "Because you're getting healthy. Yay." [laughter] Yeah.

And I actually use that as a marker for myself. Like, if I'm not improving someone's dose, if I'm not, you know, say within a year or a little more, not lowering that dose, then I'm missing something. And you know, myself, I'll kind of always go back—and not always, but you'll usually find the answer in the gut or the liver.

Or the liver.

I think we can do a series on thyroid alone. And Craig, I think it was a great idea to talk about thyroid. Just a side note real quick, I started my business, pharmacy business, on thyroid. Just a quick note, when I first started compounding, they had an issue with a product, but by then it was called Nature-Throid. Nature-Throid was a product that a lot of people used to love, right? It was a desiccated thyroid or a USP micronized commercially available product, and then overnight it went away. People started having conversations about the fact that it was probably a play by, you know, our big pharma friends to get these people to go away.

And so a lot of doctors were looking for alternative products, and that's when compounding started to provide more options for people that used to be on Nature-Throid to get access to a desiccated thyroid on the compounding side. So I used to do a lot of customers coming in, and I always—if you remember, I used to say, "Oh my gosh, the thyroid customers are the worst." And it was a joke, obviously. Why? Because they have so many things happening, it's unbelievable. They either are controlled or they're not. If they're controlled, everything is great. If they're not controlled, everything else downstream is horrible. You know, either they're tired, it's brain fog, you know, it's just—it was so difficult to deal with them. But at the same time, it opened my eyes to how important thyroid is.

So, I know Suzanne was saying she thinks 50%. I think so. I think 50% for sure is affected by thyroid disorder in some shape or form. I think, you know, when we use TSH as our main biomarker, that's failing the patients. And I remember when I first talked about reverse T3, people were like, "What are you talking about?" right? Even physicians right around me or PCPs didn't even know what reverse thyroid was, you know? It was always the first thing I always asked people, I was like, "Hey, what's a reverse T3?" and then "What are you talking about, reverse T3? I don't even know, what is that?" You know, I'm talking about regular doctors asking me what it is. But it was always the thing like, "Whoa, what is that all about? What's going on with this number?" and it usually helped them solve a lot of their problems back then.

Anyway, 2025 last year, I think they sent a letter that just kind of shook the whole industry around unapproved marketed drugs. Okay, so let's go back to the fact that no desiccated thyroid commercially available products sold in the United States right now are actually approved for it, which is crazy. We call them NDT.

So, they sent a letter saying that the FDA has a long-standing category called unapproved marketed drugs. So, they don't want to change the policy, however, they might change a few guidances towards the continuing enforcement and discretion around ending, okay, these new unapproved marketed drug products. So they sent some memos out there to the manufacturers to let them know that the FDA wasn't clear about unapproved drugs for a long time, and they're trying to find an alternative or a path to getting a lot of those unapproved marketed drugs a path, right, to actually get it approved.

You know, so when they did that, that changed the whole thing. That means that several companies now have to have an active IND, but those things take about two to five years for completion, right, from the beginning to the end. So you have a few companies out there that actually have an active IND. When you have an active IND, that means that as an API manufacturer or as a wholesaler, then you can't get access to that API anymore—which, API stands for active pharmaceutical ingredient.

So, what does it mean for the physician and prescriber? Really, nothing has changed if you're a compounder or somebody that likes to compound—and we can talk about why compounding makes the most sense for a lot of people. Well, if you're a compounder, then you've got a problem because your wholesaler can't get access to that very well. USP, we call it, yeah, USP desiccated thyroid anymore to make your compound, right? Because we used to make it, we still make it for physicians that are looking for a desiccated thyroid that comes from, you know, from a different source.

If I have a Jewish customer that's kosher, he wants a bovine source; well, we'll go get the bovine source. If we have someone that wants a different sustained-release version of it because they want more T3 throughout the day, well, we'll do a sustained-release version of it. You know, if we have somebody that wants a different ratio—because we can start talking about ratios, on T4 to T3 it's 80:20 usually. But, you know, if they want a different ratio, we can talk about ratios and then, okay, well, we're going to bump this one a little bit different, we're going to use a different source, get a higher T3 ratio to T4. You know, there's a lot more complexity and nuance customization through compounding that a lot of physicians love to use. And that's the big problem right now, is that a lot of physicians now don't know if this is going to be available for them, right.

Definitely that's an interesting area too to touch on with regard to the ratios and whatnot. And I think it's important for listeners just to understand maybe sort of broadly what the difference is between something like a Synthroid or a levothyroxine, which is just synthetic T4 relying on the body's intrinsic ability to convert that into T3, versus a product like NP Thyroid or Armour Thyroid where you're getting, again, most often in like a 4:1 ratio of T4 to T3. The T4 is like a longer-acting, sustained-release sort of formula, versus the T3 which is going to be more of an immediate release usually when the patient takes it. So there's different things out there.

Just to switch gears for a second, I think it's really also important for patients to understand what is the most common cause of hypothyroid. Sure, there's hyperthyroidism, we see it a lot, or it's relatively common, I guess, but nowhere near as common as like hypothyroid states. The most common cause of hypothyroidism is what's called Hashimoto's, which is an autoimmune condition.

And again, linking this back to everything influencing each other, why do we get autoimmunity? If we look at hormones, declining hormones—progesterone has incredible immune-balancing, immune-regulating properties. As progesterone starts to decline for women in their latter 30s as they're moving on into perimenopause, they're losing a big portion of their immune signaling right there. What do we know about autoimmunity? Well, it's way more commonplace amongst women and prevalent amongst women.

So, this is a major thing to contend with, and I start to see this—I mean, I'm sure you guys too—increasing antibodies, women starting to complain about these symptoms that ultimately turn out to be a Hashimoto's-type picture throughout perimenopause on through their later years in menopause and such.

How do you diagnose that, Craig?

Yep. So, we're looking at antibody levels: thyroid peroxidase (TPO) and thyroglobulin antibody. We're looking at the level of which these antibodies have risen in the serum, in the blood. What an antibody is, is it's an immune protein that is designed to contend with or deal with a foreign invader or a pathogen. But when the immune system becomes dysregulated for one reason or another, those immune proteins—by way of molecular mimicry or any number of other things that can happen inside the cell—can be directed in an adversarial fashion against our own tissues.

So when they start to attack the thyroid gland and you see that thyroid peroxidase—the cutoff is around like 30 or 34, but we often see them elevated into the hundreds, like several hundred, they can really start climbing, and the same is true with thyroglobulin within a different reference range—these levels start to climb. That right there is your first clue, I think, from a biomarker standpoint, that there's autoimmune signaling happening.

Ultimately, what that's going to contribute to is a decrement in thyroid function. As the thyroid tissue is destroyed, as it's attacked, becomes inflamed, then we're going to have all of the other biomarkers—the TSH, the T4, the T3—sort of fall into an abnormal pattern as well.

We're trending all these things over time, and this is an area where I really like to work with patients, because then we're starting to look at things like, how do we implement at least an elimination diet, but more stringently an autoimmune paleo diet? Well, there's an interesting peptide out there that we know—one of the ways that it works, at least in its research, is on antibodies specifically for celiac disease, and we know there's a strong correlation. In fact, there's some suggestion in the literature that it's actually malpractice if you find thyroid antibodies and you aren't looking for celiac antibodies as well.

I usually will throw in there an ANA while I'm at it just because I want to know, and because I know that long COVID is associated with elevated ANA. So, I'm sort of throwing all these things in there if I'm looking at fatigue as a new symptom in the last couple of years. I'm thinking this long COVID, you know.

It's funny because Hashimoto's is, for me, I remember it was 90% of the people literally walking into my pharmacy back then begging for Nature-Throid to save their lives and their marriage back then. It's yeah, because it's like the most undiagnosed thing, and it affects everything else because it always travels with something else. It travels with PCOS for a woman. It travels with type two diabetes or pre-diabetes. There's always—they start there and then they end with PCOS, they end with something else, right? And then they go back and trace it back to, oh, if we had looked at Hashimoto's back then, then maybe those things were not going to happen, you know? But yeah, Hashimoto's is a big deal. I mean, I think, Craig, you probably have a really busy practice just dealing with that alone, right?

Well, I mean, for the patients that do have it, it's something to contend with. I'm sort of always coming back to the diet, I'm coming back to the gut. When we talk about tight junctions, really we're talking about that junction in between colonocytes and enterocytes where there can ultimately be precipitation of leaky gut, right? And the translocation of these bacterial byproducts and other toxins that sort of leak out of the gastrointestinal tract—which is the number one interface with the outside world outside of our skin for each individual.

So those things should be maintained where they are, and as they start to translocate into the bloodstream, we have increased risk for more inflammatory signaling, plaque development within the coronary arteries and the cerebral arteries. So we want those junctions to be tight, and then what can we do to bolster that? I mean, cutting out things like grains and legumes, and limiting or entirely doing away with dairy and certain nuts and seeds. An autoimmune diet is very stringent, but when people follow it in a regimented fashion, they do very, very well.

So I'm always coming back to that with my Hashimoto's patients. It's like, okay, we tracked your antibody levels, they were coming down substantially, and then all of a sudden something happened. A lot of times, I would say a majority of times, we can trace it back to dietary indiscretion—fell off the wagon a bit. It happens for all of us, so no fault to them, but once they get back on track, things start to improve again. So the gut—looking at the gut, it's just so crucial.

You know, one of the autonomic nervous system girls here again, welcome. One of the biggest reasons for tight junction disruption is sympathetic dominance. We all have to be aware that our cortisol affecting that tight junction can really make a difference. And so, helping them figure out in their lives how to make that happen. But something that can be really stressful is not eating gluten. I mean, that would be really hard for me. I love gluten. Yeah.

So, what I try to tell my patients is, "Please just do 2 weeks off of gluten. All I need for you to do is not forever. I need two weeks, and then on the 15th day, I want you to eat all the gluten you can." Like, a bagel for breakfast, a big fat gluten sandwich for lunch, pasta for dinner—like, no gluten-free stuff, all heavy pasta stuff on the 15th day. Because then they see, and then they're like, "Okay." Right. And they see it.

Exactly. It's so hard to get them to that point because I can't tell you how many people I've seen in that scenario where I know it's gluten, but they can't put two or three days together, you know? I see people go through it—it's kind of like a phase where they attempt to do the gluten-free and they struggle more and more, and then finally somewhere down the road, years later, they do exactly what you said and they put a couple weeks together where they go gluten-free and then they eat it again, and they go, "Oh my god, this is what it was the whole time."

There's no—I just wish I could accelerate that for some people, because I have even family members right now where I'm like, "You know, it's like you haven't really gone gluten-free for a couple weeks, and the second that you do it, you're going to know, but you're going through the same process." So, but that's a great way of doing it. You're kind of forcing a forced function there. Day 15, get after it.

So, just what Dr. Free said. I mean, mine's 3 weeks, so I guess she's nicer than me. [laughter] But you know, to that point, they feel so much better that they might do it one day, but then they see the correlation. And then the other is, these young female athletes—their ACL injuries and just all these ligament injury recoveries are so much faster. If they're fighting an injury, if they will go gluten-free, their healing process is tenfold faster. And then, seeing that, they're more likely to stay also with the gluten-free. And I'm also big on potentially dairy, if that's an inflammatory reaction for them.

I'll tell you what, dairy will definitely have a reaction. I had some ice cream last night before I went to bed after not having it for a while and holy smokes—nightmares all night. That was the craziest experience ever. Um, yeah. No, that's that's wild. I mean, I think like, how many people can actually stay off of gluten for that long and actually do it? Like you said, Leonard, I think that's amazing.

Well, the one thing I wanted to bring it back to is like, we've talked a lot about stuff that's probably over the head certainly of mine and a lot of other listeners who may be just sort of wondering like, "Hey, how do I know if I have a thyroid problem? What should I be doing if I'm a patient that's coming in now, I've gone to see my primary care provider, I'm still feeling sluggish or exhausted, whatever it might be, and having all these symptoms, but they say everything's normal. What's my next move?"

I think looking for a practitioner who's going to evaluate the full picture. When it comes to thyroid labs, basically anybody who walks in my door who is curious or has some symptoms, we're doing a TSH, we're doing free T4, free T3, reverse T3, and then those two thyroid antibodies—thyroid peroxidase and thyroglobulin. Maybe it's overkill, but really in my practice, I use all of those as sort of my screening tool. I'm never like just getting a TSH and then seeing what comes back and going from there. It's just like sort of shooting in the dark at first, instead of getting the full picture.

If thyroid antibodies are elevated, then looking at the ANA, as Dr. Free mentioned, and some other things. But alongside that, right, you need to be evaluating everything else that's going to contribute. So for me, that's micronutrients, that's looking at other indicators of cell stress that could be painting the picture as to why the thyroid levels are abnormal and why the patient feels the way they do. Any good clinician is going to advocate to run these tests because it's relatively common. I mean, pretty across the board, we're seeing a lot of patients who have thyroid dysfunction in the wake of all sorts of biotoxins, environmental concerns, and post-COVID chronic fatigue, yada yada yada. So anybody who's, I think, worth their salt as a clinician can help a patient navigate that process.

And for me, when I have patients come in saying, "I was told my thyroid labs are normal," I always just say, "Well, normal simply just means a statistical average." And that's not what we're going after. Just like Dr. Free—I mean, so many providers probably think we're crazy that we want a TSH between 1 and 2, but we tell them why we want it between 1 and 2, although 3 to 4 is still considered quote-unquote normal.

And then, just explain that to them. It doesn't always have to be a pharmaceutical. I mean, I do believe that sometimes, especially in the hormone clinics, thyroid maybe is a little overprescribed, but I can tell you, like, just being simple with your zinc, your selenium, your iodine—nutraceuticals can get you a long way taking care of those micronutrients, and then just focusing on the food. I mean, making sure that the patients understand that a whole food diet can keep that TSH in that optimal range that we're looking for, instead of just being a statistical average.

So, Christy, just really quickly, if you're eating a whole food diet, it's pretty clean, and then on top of that, you're taking some sort of mineral supplement—like a daily, I take a capful of this stuff every day, it's a liquid—I should be good, right?

I mean, you need to look at your numbers, because for some people that's not—I mean, it's like we've all reiterated, you can't just—you've got to look at the numbers and you've got to track the numbers through time. I mean, you've got to trend them out.

So, we go back to like the—there's a company that actually offers this massive panel of, like, you get every single thing you can possibly ever think of. They draw so many—I've had it done—they draw so many vials, I think they had to start a new vein for me. Is that what somebody should do when they first show up to a practice?

It depends on which practice you're coming to, and it depends on what your symptoms are, and every single patient's going to be a little bit different. I've actually several times tried to create a panel that I could just do for everyone, and I just can't do it because everybody I want a little bit different. Everything that comes up when I listen to you talk, when you're sharing things, I think when it comes to the thyroid, you have to remember that the thyroid is a marker of metabolic safety, and that when your thyroid changes, when your function changes, your provider needs to be asking what's happening in the body.

That just reminds me of Leonard's Instagram video where he was—it was one of those things where they were asking you for the quick-fire, rapid response, and everything was like sort of, "It depends," or "Why? The question is why." So good.

Yeah. Sue's point sort of echoes that in my mind, and that, you know, it's going to be dependent upon the situation.

Yeah. Those are always so hard. Those questions are always so hard, especially on Q&As and panels. When somebody asks you a question, "What do I do with my patient that's doing this?" it's like, well, how do we know? We don't know anything about your patient. You know, we don't know the history, the conversations you've had, the labs they have, what they've told you. It's really hard to come up with protocols, and that's why it's so important to go see a physician. I know we talk about this all the time. But yeah, that question always gets me. So, we don't want to use the protocol approach to the thyroid thing, right? From the guy in the gym, we don't want to use that. No, that's not the way to go. That's not a protocol situation.

All right. Well, hey, obviously I think Frank's right. I think there's a lot more here. I know I'll listen to this probably 10 times to just try to keep up with you guys, but it was phenomenal. Any last thoughts from anyone that wants to cover anything before we go?

Just say don't overlook thyroid. You know, advocate for getting worked up, especially if you're having symptoms, or if you are sort of in that midlife phase where you just want to know that everything's working as optimally as it could be—advocate for a full panel. And you know, something like one of those panels that you were talking about, not always a bad idea. Maybe not always necessary, but not always a bad idea. It's data in your back pocket. You know, it's information to sort of take with you and use it for what you will.

Yeah. One thing I would say about though, the question I have with regards to that is: You get that panel, but you take it to a provider who thinks that the ranges are different than what you guys are talking about, how valuable is that lab panel to somebody who's not looking at it the way that you are?

Well, you've got to come to Sue or Christy or myself. Man, I don't know how you guys are going to see all these patients.

I think it depends on whether you're trying to be optimal or you're trying to be normal.

Well, you know, it's funny, you always say biohacker, right? So, the biohackers, but are those just optimizers, the patients that you see? Because I think of the biohackers—like last night, I sent to Leonard and Frank last night, there's a guy who claims to be the original biohacker claiming that creatine doesn't get absorbed into the system unless it's heated in his coffee that he sells. Yeah, exactly. That is more—well, I'm not going to get into it because whatever. Whatever, dude.

So hey, this has been a great episode as always. You guys are the best. I learned so much, and I'm sure everyone who is also watching it—I just sit here and just say to myself, "Wow." Amazing, amazing information. So, thank you so much. And for those of you that are listening, please come back. The next episode, 17, is going to be absolutely awesome. Please remember to like, share, and subscribe. And as Craig said, think about your thyroid. We'll catch you on the next one.