373 – Thyroid function & hypothyroidism: how new approaches are transforming care

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey everyone, welcome to "The Drive" podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:11 – 11:08

   How the thyroid produces, stores, & activates hormones like T4 & T3 to finely regulate thyroid activity

   1. PAPeter Attia0:11

      Tony, thank you so much for making the trip up to Austin. Uh.

   2. ABAntonio Bianco0:14

      My pleasure.

   3. PAPeter Attia0:15

      I guess Galveston's not that far, huh?

   4. ABAntonio Bianco0:17

      No, it's a coup- may- it three hours. It was pretty easy last night.

   5. PAPeter Attia0:22

      All right. So you're the dean of the medical school there.

   6. ABAntonio Bianco0:24

      That's right.

   7. PAPeter Attia0:24

      You're running a lab. Um, tell me a little bit about what your research focus is on and maybe even what got you interested in studying the thyroid system.

   8. ABAntonio Bianco0:34

      Uh, well, my research right now is trying to understand what thyroid hormone does. And by understanding what it does in different tissues, we will be able to serve patients that don't have sufficient thyroid hormone, patients with hypothyroidism. So we go at the level of-- at the tissue level, so we-- you know what it does in the-- what does it do in the liver? What does it do in the heart? But then we go into the cell level, and we are currently looking at how thyroid hormone affects the folding of the chromatin, and because how it does it, it regulates gene expression. Basically, that's how T3 or thyroid hormone acts, by regulating different genes. And because the genes are, you know, basically the essence of the, the cell functioning, by regulating the expression of those genes, it changes the way the cell behaves. And that has a, a important consequence for the whole tissue and for the organ and for the body.

   9. PAPeter Attia1:31

      So maybe let's start with the, uh, the stuff that is largely known-

   10. ABAntonio Bianco1:37

       Mm-hmm

   11. PAPeter Attia1:37

       ... about the thyroid.

   12. ABAntonio Bianco1:38

       Mm-hmm.

   13. PAPeter Attia1:38

       Um, so I'll, I'll, I'll say a few things just to get us pointed in the right direction, but, but obviously I want you to sort of correct me and/or take us into a little bit more depth. So I suspect many people know that they have a gland that sits over-

   14. ABAntonio Bianco1:53

       Mm-hmm

   15. PAPeter Attia1:53

       ... the, the voice box called the thyroid gland. Um, that's probably what most people know. Most people also probably know that it produces a hormone.

   16. ABAntonio Bianco2:03

       Mm-hmm.

   17. PAPeter Attia2:04

       Some people might know that that hormone is actually inactive, uh, abbreviated T4-

   18. ABAntonio Bianco2:09

       Right

   19. PAPeter Attia2:09

       ... because it has four iodines on it. And that this, this... Now we're getting maybe [chuckles] past what most people would know, but enzymes in the body take one of those iodines off and make an active form of that hormone that we abbreviate T3.

   20. ABAntonio Bianco2:25

       Right.

   21. PAPeter Attia2:26

       And I suspect that a number of people watching or listening realize that that hormone is very important, and it has properties that regulate energy expenditure, body temperature-

   22. ABAntonio Bianco2:39

       Mm-hmm

   23. PAPeter Attia2:39

       ... mood, sleep, all sorts of things.

   24. ABAntonio Bianco2:41

       Right.

   25. PAPeter Attia2:42

       I think the final thing I'll say that is probably somewhat common knowledge is that it is not entirely uncommon that some people don't seem to make enough of that hormone for one reason or another. We're gonna talk about all of these things-

   26. ABAntonio Bianco2:55

       Right

   27. PAPeter Attia2:55

       ... of course. And that as a result of that, they have to supplement that hormone.

   28. ABAntonio Bianco2:59

       Right.

   29. PAPeter Attia2:59

       And that condition could be referred to as hypothyroidism. And there are many people listening to us, I would ven- venture that there are tens of thousands of people listening to us right now that would identify as having hypothyroidism and that are-

   30. ABAntonio Bianco3:12

       Right
3. 11:08 – 18:07

   How fasting alters thyroid hormones to conserve energy

   1. ABAntonio Bianco11:08

      inactivated.

   2. PAPeter Attia11:09

      So I'm gonna give you a, a true scenario, and I want you to use it as an example to explain to people why that could happen.

   3. ABAntonio Bianco11:16

      Mm-hmm.

   4. PAPeter Attia11:16

      So this is a very extreme case. Now, I used to do a lot of fasting.

   5. ABAntonio Bianco11:20

      Mm-hmm.

   6. PAPeter Attia11:21

      So I would fast for up to seven to 10 days every quarter.

   7. ABAntonio Bianco11:25

      Mm-hmm.

   8. PAPeter Attia11:26

      And I used to check my blood work before and after. So I'll give you my thyroid numbers, typical thyroid numbers-

   9. ABAntonio Bianco11:33

      Mm-hmm

   10. PAPeter Attia11:33

       ... at the beginning before I started fasting and at the end, keeping in mind we haven't explained what TSH is yet-

   11. ABAntonio Bianco11:39

       Mm-hmm

   12. PAPeter Attia11:39

       ... and we'll come back to it, but just to get the T3, T4 part. So before a fast, I might have a TSH of two-

   13. ABAntonio Bianco11:46

       Mm-hmm

   14. PAPeter Attia11:46

       ... a free T3 of .3 and a reverse T3 of 10. After the fast, the TSH would go to seven The free T3 would be .2.

   15. ABAntonio Bianco12:05

       Mm-hmm.

   16. PAPeter Attia12:05

       So it would go down by 50%. The reverse T3 would be 35.

   17. ABAntonio Bianco12:11

       Mm-hmm.

   18. PAPeter Attia12:12

       So what is happening in my body that would lead to those dramatic changes in those thyroid hormones?

   19. ABAntonio Bianco12:19

       So what's happening is that the hypothalamus, which is the center in the brain that regulates the thyroid function, is detecting that you're not eating. How does it detect that? Your insulin levels are low, your leptin levels are coming down, and those are cues to the hypothalamus to say, "Well, wait a minute. There's not a lot of food coming in here." Thyroid hormone accelerates energy expenditure. Thyroid hormone is all about burning energy, burning sugar, burning protein. So the hypothalamus says, "Well, I have to reduce, to take my foot off the gas here so that even though there's less food coming in," in your case, nothing, "we not-- we, we're gonna reduce the rate at which I'm burning the fuel here." And so your TSH, even though it's within the normal range, now is inappropriately normal because your T4 came down. You didn't mention your T4-

   20. PAPeter Attia13:22

       Yep

   21. ABAntonio Bianco13:22

       ... but T4 for certainly would come down.

   22. PAPeter Attia13:24

       For certain come down, and that's why the TSH went up.

   23. ABAntonio Bianco13:27

       Right, but slightly.

   24. PAPeter Attia13:28

       Yep.

   25. ABAntonio Bianco13:29

       You know, i- if you had... Normally, if you have a significant drop in T4, the TSH should go up much more.

   26. PAPeter Attia13:36

       Got it.

   27. ABAntonio Bianco13:36

       It's... The TSH is not going up so much because the hypothalamus is telling TSH, "Don't go up." The-- It's-- There's no need because right now we want to slow things down. So your TSH is inappropriately normal, even though the T4 is down, the T3 is down. Why is T3 down? Your thyroid is secreting less thyroid hor- less T4, but also a little bit of T3. It's making less T3 as well. But most importantly, the deiodinase pathway, we just, we just mentioned that, the T4 now is being converted preferentially to reverse T3 and not so much to T3, and that's why reverse T3 goes up. Now, there's another reason for why reverse T3 is up, because reverse T3 has a very short half-life, even shorter than T3, just a few hours. Reverse T3 is cleared through the D1 pathway. You mentioned there are three deiodinases. The D1 is very important in clearing reverse T3 from the circulation. And the interesting thing is that D1 is richly expressed in the liver, very sensitive to insulin and carbohydrates. If you eating a lot of carbohydrates, your D1 in the liver is gonna go up, and the opposite when you don't eat so much. So what's happening is D1 activity is coming down in the liver because you're not eating. Insulin down, carbohydrates down. And because D1 metabolizes reverse T3, reverse T3 builds up in the blood. So not only there's more reverse T3 production, but there's also less reverse T3 metabolism. And so that's why reverse T3 goes up. T3 is down just because it's not being produced so much, and your energy expenditure is going down. So it's common to see individuals that fast that in the first few days they lose significant amount of body weight, but then it reaches a plateau. And a, a lot of people, some studies attribute this plateau to the fact that the thyroid hormone levels are down because you, you are equating the amount of calorie you're intaking with the, with your energy expenditure. You're reducing it.

   28. PAPeter Attia16:02

       And so is that ratio, which some people have talked about, the ratio of reverse... Uh, pardon me, of free T3 to reverse T3, that rising level of that ratio, is that a poor man's proxy of aggregate thyroid activity in the body, or is that just too coarse a manner to look at it? So if I go back to my numbers there, I think I started out at a ratio of .3-

   29. ABAntonio Bianco16:25

       Mm-hmm

   30. PAPeter Attia16:25

       ... or what- you know, w- you could normalize it, but, you know, .3 over 10. Um, so call it 0.03, um, or 3%. And then, you know, I think it goes to 2 over 30. I mean, then it, you know, it's basically falling by 50% and uh, doing the math. Like, it's, it goes down by a sixth or so.
4. 18:07 – 22:59

   Action of the deiodinases: how D1, D2, & D3 enzymes control the activation & inactivation of thyroid hormones

   1. ABAntonio Bianco18:07

      it's useful.

   2. PAPeter Attia18:07

      Now, you mentioned that this was D1.

   3. ABAntonio Bianco18:09

      Yes.

   4. PAPeter Attia18:10

      What do... Tell us about D2 and D3. Where do they reside? What do they do?

   5. ABAntonio Bianco18:14

      Okay. D2 works very similarly to D1. However, D2 is a superb enzyme. D2 is the enzyme. It has... Just so you know, D2 has 1,000-fold more affinity for T4 than D1. D1 is a lousy enzyme, even though D1, uh, you know, it was the first one discovered in the liver and the kidneys, but D2 is so much more efficient. It's, it's like the supercharged enzyme. And so if you ask, uh, okay, the T3 that's produced outside of the thyroid, most T3 is produced outside of the thyroid. Who produces T3 outside of thyroid? Is it D1 or D2? Studies done in the '70s show that is D2 pathway. D2 makes about 80% of the T3 in the, in-- that's made outside of the thyroid gland. D1 makes only 20%. Although w- when we talk about hypothyroidism, there could be a role for D1. I will talk about it.

   6. PAPeter Attia19:20

      So D1 is making both T3 and reverse T3.

   7. ABAntonio Bianco19:24

      Makes a little bit of reverse T3, yes. But the king of reverse T3 is the third deiodinase, is D3.

   8. PAPeter Attia19:32

      Ah.

   9. ABAntonio Bianco19:33

      So D1 and D2, they activate thyroid hormone mostly. D3 only does one thing, inactivates thyroid hormone. DT, D3 kills everything. D3 takes T3 and transforms it into T2, a dead molecule. So where does T3 go? T3 goes to D3, and it's killed completely. D3 is very effective enzyme. It's very... has high affinity for T3. So it also takes T4 and make reverse T3. So D3 inactivates T3 and makes sure T4 doesn't do anything, takes T4 and make reverse T3. So D1 makes reverse T3, but very little because, uh, the affinity of D1 for T4-

   10. PAPeter Attia20:23

       Very low

   11. ABAntonio Bianco20:24

       ... is not that great. Now D-- So when you think about it, D3 and D2 are the most powerful deiodinases. D2 making T3, D3 eliminating, inactivating thyroid hormone.

   12. PAPeter Attia20:37

       Mostly through making D2.

   13. ABAntonio Bianco20:39

       That's correct. It's, it has to be D2.

   14. PAPeter Attia20:41

       So which enzyme makes the most D3? Uh, pardon me, makes the most reverse T3?

   15. ABAntonio Bianco20:46

       D3.

   16. PAPeter Attia20:47

       Okay. So D3 is basically a dead pathway either going... And what determines if it goes down D2, which just takes the hormone out of pocket, versus d- making reverse T3, which actually puts another molecule in the receptor that prevents T3 from getting there? It seems that making reverse T3 is actually more anti-thyroid.

   17. ABAntonio Bianco21:09

       No. So, so reverse T3 doesn't bind to the pocket.

   18. PAPeter Attia21:13

       It does not?

   19. ABAntonio Bianco21:13

       No.

   20. PAPeter Attia21:14

       So what's, so what's the difference in futility of reverse T3 and D2?

   21. ABAntonio Bianco21:22

       Uh, uh, what do you, I mean, I'm not-

   22. PAPeter Attia21:23

       Well, by that I mean, so you have a molecule of T3-

   23. ABAntonio Bianco21:27

       Okay, T3

   24. PAPeter Attia21:27

       ... which has all of this biologic activity.

   25. ABAntonio Bianco21:29

       Okay. Yes.

   26. PAPeter Attia21:30

       What is the difference between turning that into reverse T3 versus turning it into-

   27. ABAntonio Bianco21:35

       Ah

   28. PAPeter Attia21:35

       ... D2?

   29. ABAntonio Bianco21:36

       No, no, no. T2. No.

   30. PAPeter Attia21:38

       Sorry, sorry, T2.
5. 22:59 – 34:12

   The normal function of thyroid hormone & the roles of the hypothalamus, pituitary gland, & deiodinases in maintaining hormonal balance

   1. PAPeter Attia22:59

      So anything else we want to say about the normal function of thyroid hormone before we start to talk about the two extreme states, hyper and hypo?

   2. ABAntonio Bianco23:10

      Well-

   3. PAPeter Attia23:10

      What else do we need to... I guess we, we should probably go back and say a little bit more about the hypothalamus and TSH regulation.

   4. ABAntonio Bianco23:16

      Right. Yeah. No, the hypothalamus is the key to everything here, right? So the hypothalamus produces this hormone that's called TRH or TSH-releasing hormone, and it acts... It's a, it's a small peptide that is released in the blood that abates the hypothalamus and immediately comes into the pituitary gland. The pituitary gland is where TSH is made. So if, if the hypothalamus is somehow destroyed, either by an accident or by a tumor or by surgery, then TSH is not gonna be produced because you need TRH to stimulate TSH, and that's a problem. That's called central hypothyroidism, and we can talk about it later because this is... Many patients claim they have central hypothyroidism, and it's important that we, we talk about it a little bit. So central hypothyroidism is when the pituitary gland is not producing sufficient amounts of TSH. And why TSH is important? Only because it stimulates the thyroid to function. Uh, and this is something I've seen a lot in, in different, uh Uh, patient groups discussing, "Oh, my TSH is this. TSH is doing..." No, TSH doesn't do anything. None of the symptoms of hypothyroidism can be attributed to changes in TSH. It has to work through the thyroid gland. So the TSH stimulates the thyroid to grow, to function, to secrete thyroid hormones.

   5. PAPeter Attia24:44

      So, uh, let me just restate that-

   6. ABAntonio Bianco24:46

      Yeah

   7. PAPeter Attia24:46

      ... so that people are following. Um, when TSH is very, very high... So normal range would be, I'm just saying-

   8. ABAntonio Bianco24:54

      Yeah

   9. PAPeter Attia24:54

      ... let's say normal range in the laboratory is .5 to four, something like that.

   10. ABAntonio Bianco24:58

       Got it. Yes.

   11. PAPeter Attia24:58

       Okay. So if your TSH is unmeasurable-

   12. ABAntonio Bianco25:03

       Mm-hmm

   13. PAPeter Attia25:04

       ... we're gonna talk about what this implies. It means there, you have too much thyroid hormone.

   14. ABAntonio Bianco25:09

       Right.

   15. PAPeter Attia25:10

       But the actual symptoms you have are from too much thyroid, not from too little TSH.

   16. ABAntonio Bianco25:14

       That's correct.

   17. PAPeter Attia25:15

       Conversely, if a patient shows up and their TSH is 75, which you and I have both seen, the symptoms they feel, which are usually pretty significant, are not because of the high TSH-

   18. ABAntonio Bianco25:28

       Correct

   19. PAPeter Attia25:29

       ... it's because the complete lack of thyroid hormone.

   20. ABAntonio Bianco25:31

       That's right.

   21. PAPeter Attia25:32

       Okay. Just wanted to make sure that was clear for the listener.

   22. ABAntonio Bianco25:34

       No, absolutely.

   23. PAPeter Attia25:35

       Let's go back and restate the, the, the, the whole thing. You have a hypothalamus, you have a pituitary, you have a thyroid. The hypothalamus secretes TRH, thyroid-releasing hormone-

   24. ABAntonio Bianco25:46

       Right

   25. PAPeter Attia25:47

       ... to the pituitary. The pituitary secretes TSH, thyroid-stimulating hormone, to the thyroid gland to secrete T4.

   26. ABAntonio Bianco25:56

       That's correct. Absolutely. And, and the, and the what's unique about the thyroid is that its levels in the circulation, if you look at T4 and T3 levels, they change very little over during the day or during the week, even d- during the year. Uh, there's some minimal fluctuation, maybe 10%, 15%.

   27. PAPeter Attia26:19

       Outside of these extreme events like illness or fasting-

   28. ABAntonio Bianco26:21

       Oh, yeah. Oh, yeah

   29. PAPeter Attia26:21

       ... or things like that.

   30. ABAntonio Bianco26:22

       In normal thyroid function.
6. 34:12 – 37:03

   Why understanding thyroid physiology is essential for proper diagnosis & treatment of hypothyroidism

   1. PAPeter Attia34:12

      Yes. Well, we're... For the, for the folks listening now who are wondering, "Why are you guys going into so much physiology?" You s- you have to-

   2. ABAntonio Bianco34:19

      That's right

   3. PAPeter Attia34:19

      ... if you want to understand how to treat this.

   4. ABAntonio Bianco34:22

      That's exactly right.

   5. PAPeter Attia34:23

      You can't... Especially with all of the different schools of thought around treating this, to put it kindly, we must be able to understand this physiology to understand what is a genuine therapy, what is sort of voodoo medicine, and what is potentially harmful.

   6. ABAntonio Bianco34:39

      What, what you just said is so important because, uh, unfortunately, a lot of people that talk about treatment of hypothyroidism, uh, has incomplete understanding of thyroid physiology. And I don't mean to criticize any of my colleagues, uh, in saying that, but it's a fact. And things that you hear, y- it, it... that is just, uh, you know, from a different world. For example, you j- uh, just we talk about T3 so much. T3 is the biologically active hormone. T3 is the one that, uh... Uh, but the s- a strong school of thought says, "Never measure T3. You don't measure T3. Why would you measure T3?" But this is so, uh... It makes absolute no sense be- if you think about all of we just discussed for this half hour, I mean, why would you not measure T3? It's the biologically active hormone. So it is... And, and I attribute this to incomplete understanding of thyroid physiology. That's it. I mean, it's not simple. Uh, and I have to say, I've been studying the thyroid for about forty years, forty-five years. It took me a while to understand. I mean, to m- to, to put together dots, important dots, it took me decades because I was going exactly through, listening to exactly those lines of thoughts. "Oh, my T3, you don't have..." But then you start looking, "But wait a minute. In, in my studies in, in the lab, I look at T3. It's the only thing I look." But then when I go clinical, when I, when I'm taking to, talking to my patient, I don't care about T3. And then my patients start asking me, "Doctor, shouldn't we measure T3?"

   7. PAPeter Attia36:29

      [chuckles]

   8. ABAntonio Bianco36:30

      "Uh, no, don't worry about it. No, no, we just measure T- free T4 and TSH." "But why?" "Don't worry about it." And so this is so, I mean, and, uh, this is so important, and I lived through this And, and that's why I became so focused on helping patients with hypothyroidism because I myself thought I did a disservice to them, to many of my patients, because I was just repeating what I learned, uh, from the people that, that unfortunately did not take into consideration thyroid physiology.

7. 37:03 – 45:40

   Testing for thyroid hormones: understanding free vs. total levels, the limitations of current T3 assays, best practices

   1. PAPeter Attia37:03

      So when we do a blood test on a patient-

   2. ABAntonio Bianco37:06

      Mm-hmm

   3. PAPeter Attia37:06

      ... and we are measuring... Let's say we are measuring four things, TSH, free T3, free T4, reverse T3.

   4. ABAntonio Bianco37:16

      Mm-hmm.

   5. PAPeter Attia37:17

      There are two other things that are typically offered, which is T3 and T4.

   6. ABAntonio Bianco37:22

      Correct.

   7. PAPeter Attia37:22

      Explain to people the difference between the T3, T4 assay and the free T3-

   8. ABAntonio Bianco37:26

      Mm-hmm

   9. PAPeter Attia37:27

      ... free T4 assay, because earlier when I gave you numbers, I didn't even mention the T3. I went straight to the free T3.

   10. ABAntonio Bianco37:32

       Right. So TSH is not affected by what I'm going to explain. So T3 and T4 are affected. So most T3 and T4 in the circulation, when I say most, I mean 99.5% are not in the free form. They're bound to proteins. They're proteins in the blood that love T3 and T4, so they, they bi- they trap T3 and T4. Now, these are large proteins, uh, albumin. Uh, uh, there are other proteins, but th- these are large proteins. Now-

   11. PAPeter Attia38:09

       Is there an equivalent of sex hormone binding globulin?

   12. ABAntonio Bianco38:11

       Yes, it's very similar. They're produced in, in the, in the liver. You know, the most important is thyroxine-binding glob- TBG, for example, is the thyroxine-binding globulin, which binds both T4 and T3. I mean, they like more T4 than they like T3, but for practical purposes, uh, 99 point... You know, this is all bound.

   13. PAPeter Attia38:32

       And once bound to protein, they're not active.

   14. ABAntonio Bianco38:34

       No.

   15. PAPeter Attia38:34

       They have to become unbound.

   16. ABAntonio Bianco38:35

       Exactly. They can't go into the tissue because they had to go through the membrane, and if they're bound, like, you can't go. It's like going through a door driving a car. You can't, right? So you have to step out of the car to go through a door. That's exactly what thyroid hormone does. So there's a, a tiny little fraction of thyroid hormone that's free, that's outside of this pro- and that is the fraction that gets into the tissues that is biologically active. Now, it would be... You know, they're very similar, measuring total T3 or free T3, total T4 or free T4. However, uh, th- there's a problem. These proteins can change, and estrogen, for example, affects the levels of thyroxine-binding TBG. So th- there are a s- a number of conditions that can affect the total amount of T4 that's bound, but it doesn't affect the free fraction. So then from a diagnostic point of view, we always look at... We like to look at the free fraction because that's telling you how much actually is getting into the tissues, right? It doesn't really matter how much. The, the extreme example is during pregnancy. Uh, because of the high levels of estrogen, TBG goes up, T4, total T4 goes up. The, uh, uh, a T4 during pregnancy can be a normal T... 14, 15, even though the upper limit of normal is about 12. You can tolerate. But the free fraction is normal, so we don't, we don't have to worry about it. It's not a problem. Therefore, uh, doctors like to ask for TSH, free T4, and free T3. Now, free T3 and T3 is still, uh... We, we need to talk about measuring T3. Neither one of the tests are good. Because we never cared about T3, the assays that we developed for T3 and free T3 are not gold standards. Free T4 is a gold standard method. Free T3 and T3 are not. They have a lot of variability. The interassay coefficient is high for these measurements. And so, uh, this is a typical hormone that we need to use mass spec. And there are studies shown that when you use mass spec is that when you have a real number for T3 in the circulation. Now, you can measure free T3 or total T3 for, for mass spec. That, that's either one.

   17. PAPeter Attia41:16

       So sorry, just to be clear, Tony, let me back up. You're saying when you go to LabCorp, Quest, or all of the reputable labs out there and you... and the doctor checks off T4, free T4, it defaults into a CLIA-approved mass spec assay.

   18. ABAntonio Bianco41:31

       No. No, the T4 is a, is an immunoassay.

   19. PAPeter Attia41:34

       T4 is immunoassay.

   20. ABAntonio Bianco41:35

       All... No, all of these assays are immunoassays. I, I just... I may, I misspoke. Uh, I, I did not explain myself clearly. The T3 is an immunoassay. Free T3 is immunoa- all of these are immunoassays. However, the immunoassays for T3 are not good.

   21. PAPeter Attia41:53

       But the immunoassay for T4 is good.

   22. ABAntonio Bianco41:55

       Yes. Yes.

   23. PAPeter Attia41:55

       Now, when I go to LabCorp, is there an opportunity... So I'll give you an example. We do, we never check estrogen, testosterone on an immunoassay.

   24. ABAntonio Bianco42:04

       That's go-

   25. PAPeter Attia42:05

       We throw that assay-

   26. ABAntonio Bianco42:06

       I was just gonna say that

   27. PAPeter Attia42:06

       ... in the garbage-

   28. ABAntonio Bianco42:07

       Exactly

   29. PAPeter Attia42:08

       ... and we specify LC-MS always.

   30. ABAntonio Bianco42:09

       Mass spec. Exactly. That's exactly what we need to do for T3.
8. 45:40 – 48:23

   Genetic & sex-based variability in thyroid hormone regulation & their limited clinical significance

   1. PAPeter Attia45:41

      any other things we wanna talk about? Uh, I'll give you an example. We know that genetics play a significant role in androgens on the male side, right? There are just... And, and we think maybe it has to do with androgen receptor density-

   2. ABAntonio Bianco45:58

      Mm-hmm

   3. PAPeter Attia45:59

      ... and that some people have more androgen receptors, and therefore they need and make more testosterone-

   4. ABAntonio Bianco46:04

      Mm-hmm

   5. PAPeter Attia46:04

      ... than others, et cetera. Do-- H-how much genetic variability and, d- uh, and, and sort of germline ger- uh, variability is there in thyroid hormone?

   6. ABAntonio Bianco46:14

      There's a little bit. I mean, I, I would have said many years ago that there's not much, but more, more recently, folks, especially folks from the Netherlands, have published studies showing that there is some genetical importance influence. But is this clinically relevant? That's that question. Uh, I don't think that we are changing anything based on genetics. I, I don't need to look at your genes to, to say, "Well, this TSH is normal or not." Uh, it's... Just look at the range in TSH, point four to four or five, what you just... It's a broad range, right? So especially-- When you care about this, when you're treating someone, what, what is the T- where should I put this TSH? Is it four okay, or do I have to go to point eight? That's when genetics could help.

   7. PAPeter Attia47:05

      Mm-hmm.

   8. ABAntonio Bianco47:05

      And, but the, the magnitude of the effect is not that great. So it would be interesting to, to, to... And I think today we can do this with electronic medical record that they keep for years the, the, your results. I mean, it, it would be good to know how much my TSH was, uh, uh, b- if I develop hypothyroidism, my previous TSH is where I wanna be. But do we do this? Not so much. Uh, I think that, uh, this is really maybe in some specific cases. So the answer is there is genetic influence. However, I'm not sure that this is going to be clinically relevant at this point.

   9. PAPeter Attia47:48

      And then the final question before we get into pathology-

   10. ABAntonio Bianco47:51

       Mm-hmm

   11. PAPeter Attia47:51

       ... is male-female differences.

   12. ABAntonio Bianco47:53

       Mm-hmm. A little bit. Uh, not, not great differences. Uh, the TSH range in women are broader than male. Male, the, uh, men t-tend to keep a tighter control of the thyroid gland. Uh, you see more variability in terms of the female thyroid function tests. But again, is this clinically relevant? I, I don't believe so.

   13. PAPeter Attia48:17

       Okay. So now let's shift gears.

   14. ABAntonio Bianco48:20

       Mm-hmm.

   15. PAPeter Attia48:20

       And high level,

9. 48:23 – 1:00:10

   Hyperthyroidism: causes, symptoms, diagnosis, & treatment options

   1. PAPeter Attia48:23

      what is the split between hyperfunctioning thyroid and hypofunctioning thyroid? It, it would seem to me as a non-endocrinologist, I would see more hypo than hyper.

   2. ABAntonio Bianco48:36

      Mm-hmm.

   3. PAPeter Attia48:36

      But what's the division between them?

   4. ABAntonio Bianco48:37

      Absolutely. Uh, I think that, uh... Well, the, if you ask the, you know, the prevalence of hypothyroidism in this country is You know, depending on the, the age of the population you're looking, uh, we think there are about 20 million patients with hypothyroidism, so it would be around 4 to 5% of the adult population. Now, hyperthyroidism, you're talking about thousands. You're not talking about millions. Uh, maybe a few hundred thousands, maybe... Uh, it, it's really a much rarer condition than it is hypothyroidism. It is, uh, you know, I would see m- maybe one hyperthyroid or two hyperthyroids, uh, per month at the same time that I will see 40 patients with hypothyroidism. So it's really-

   5. PAPeter Attia49:35

      Yeah

   6. ABAntonio Bianco49:35

      ... a, a-

   7. PAPeter Attia49:36

      Yeah. Specific

   8. ABAntonio Bianco49:36

      ... it's not rare, but it is certainly less common.

   9. PAPeter Attia49:40

      Maybe let's start with hyperthyroidism-

   10. ABAntonio Bianco49:42

       Mm-hmm

   11. PAPeter Attia49:43

       ... to just get it off the table.

   12. ABAntonio Bianco49:44

       Sure.

   13. PAPeter Attia49:44

       Um, 'cause obviously it's not what we're gonna spend the bulk of our time on. Um, what are the common causes for hyperthyroidism?

   14. ABAntonio Bianco49:52

       Uh, you have two major causes. One, uh, is an autoimmune disease called Graves' disease. It is when the body produces an antibody that binds to the thyroid gland, and it binds the same place where TSH binds. So the thyroid thinks that, "Oh, there's a lot of TSH, so let me start working." So it's an antibody that stimulates the thyroid. The, the thyroid doesn't know the difference between this antibody and the TSH. So the whole thyroid gland grows homogeneously, producing a lot of thyroid hormone. So you have a hyperfunctioning. So the, it produces a lot and secretes a lot, so you have high levels of T4 and high levels of T3 in the circulation. And all the... Now, all of a sudden, all the tissues are exposed to an excess of thyroid hormone. They were used to a situation in those hormones that never change. They're super stable, and now they have two or threefold higher levels of thyroid hormone. So you will see patients complaining of heart, heart palpitation. That's, that, that's the number one symptom. Patient, for any exercise, anything, the heart will just pound very heavily. Uh, weakness is also seen in hyperthyroid patients. Jittery, patients are really agitated. They might have difficulty sleeping. They're very, uh, triggered by anything. They're very, uh, responsive. The reflexes are very rapid, very fast. So, and they lose weight. So typically, a patient that, uh, has hyperthyroidism will lose significant amount of weight. And, you know, it's interesting. You frequently make the diagnosis as you shake hands with the patient. You're gonna see that hand that's warm, uh, very soft, and, uh, wet because they're sweating. They're producing a lot of heat. Remember, thyroid hormone stimulates energy expenditure, so they're burning calories. And you c- you can just take their hand and you see that they're, that uncontrolled hyperthyroidism is going on. So that's one type of hyperthyroidism.

   15. PAPeter Attia52:01

       And, and just to make the diagnosis, to confirm it, you're gonna draw blood. You're gonna see that their TSH is basically-

   16. ABAntonio Bianco52:08

       Suppressed

   17. PAPeter Attia52:08

       ... zero.

   18. ABAntonio Bianco52:08

       Zero, exactly.

   19. PAPeter Attia52:09

       Because the brain is saying, "There's too much thyroid hormone."

   20. ABAntonio Bianco52:11

       That's exactly right.

   21. PAPeter Attia52:12

       "Let's turn this off." You're gonna draw for the antibody?

   22. ABAntonio Bianco52:16

       Yes. You, you should. Yes.

   23. PAPeter Attia52:18

       Yep.

   24. ABAntonio Bianco52:18

       You will try to measure antibodies to confirm because it could be another type of hyperthyroidism. That's how you're gonna distinguish. But you're gonna measure free T4 and T3, and you're gonna see both elevated. Free T4, free T3 or total T3, you're gonna see everything elevated. And the antibody positivity, and it's called TRAb, or there are different forms of antibodies, methods that you can measure. But that closes diagnosis of Graves' disease. Now-

   25. PAPeter Attia52:48

       And the treatment for that?

   26. ABAntonio Bianco52:50

       A treatment is you're gonna give a drug that inhibits the thyroid gland. That's the number one, is the medical treatment. There, there are drugs. There are basically two types of drug. We try to use one type of drug that inhibits the enzyme that puts the iodine into the hormone. So there's no way that gland is gonna produce thyroid hormone because it's inhibiting that in- that step that's critical. So you're gonna reduce the production of thyroid hormone. Uh, there are other forms of treatment as well. Uh, there's surgical treatment. Patients can be, uh, use the drug for a couple of months, bring down the thyroid hormone levels, and then go into surgery to remove, either remove the whole thyroid or three-quarters of the thyroid because you're gonna, uh, you know, s- reduce the amount of mass of gland that's producing thyroid hormone. And the third form of treatment is radiation, uh-

   27. PAPeter Attia53:47

       Radioactive iodine

   28. ABAntonio Bianco53:48

       ... radioactive iodine. Uh, you just take a dose of radioactive iodine, and that will just kill. Because it concentrates only on the thyroid, that will kill the thyroid gland. So it's intere-

   29. PAPeter Attia54:00

       What are the pros and cons of complete surgical removal versus-

   30. ABAntonio Bianco54:03

       Right
10. 1:00:10 – 1:09:34

    Hypothyroidism: diagnosis & autoimmune causes of hypothyroidism

    1. PAPeter Attia1:00:10

       So now let's talk about hypothyroidism, which is obviously far more common.

    2. ABAntonio Bianco1:00:17

       Mm-hmm.

    3. PAPeter Attia1:00:17

       This is the, the, you know, the so-called bread and butter of the-

    4. ABAntonio Bianco1:00:20

       Yep

    5. PAPeter Attia1:00:20

       ... endocrinologist. But there's also many etiologies, including some for which there's no identifiable cause, right?

    6. ABAntonio Bianco1:00:28

       Right.

    7. PAPeter Attia1:00:29

       So walk through the... Let's start with the horses and go to the zebras, right? What are the common, most common things that lead a patient to show up verse... Actually, let me take a step back. I wanna reframe it this way. How often is the diagnosis of hypothyroidism made from symptoms where a patient presents to their primary care doctor and says, "I feel bad for the following reasons, versus on an annual screening test-

    8. ABAntonio Bianco1:00:59

       Mm-hmm

    9. PAPeter Attia1:00:59

       ... something shows up, usually a very elevated TSH, that then, uh, warrants further investigation. What's the breakdown between those two scenarios?

    10. ABAntonio Bianco1:01:08

        Well, that, that an- the answer evolved over time, right? It used to be when I started, uh, doing medicine, you know, seeing patients decades ago, you would actually diagnose or make the hypothesis, "Oh, this patient might have hypothyroidism because of the symptoms." Today, I mean, I cannot tell you the last time I, I made the diagnosis of hypothyroidism just because everyone, uh, it, it's so easy to-

    11. PAPeter Attia1:01:34

        Everyone's showing up with labs

    12. ABAntonio Bianco1:01:35

        ... TSH le- TSH is used as a routine test. It's so good, the test, that you pick up everything. So even before it starts, has clinical manifestations of hypothyroidism, you already have a TSH seven, eight, and you start to investigate. So it's rare to see patients that come, uh, with symptoms of hypothyroidism and the diag- and to make the diagnosis. In most cases today, we have an elevated, a finding of elevated TSH. Now, it is possible that if you go to a underserved population that don't have primary care physician, they don't go for annual checkups, those patients might dev- might develop hypothyroidism and present clinically, uh, to their patients, to their doctors. Now, the most cause, the bread and butter hypothyroidism is an autoimmune disease. Again, antibodies that are produced by the patient's body against the thyroid. The patient cannot, does not recognize the thyroid as self and wants to destroy it. So the, the immune system will target the thyroid gland, will destroy that gland. That's called, uh, uh, Hashimoto's disease or an autoimmune disease of the thyroid gland. There's some level of cellular infiltration as well. You're gonna find lots of lymphocytes, uh, destroying the thyroid as well. Uh, and as a result, the size of the thyroid reduces. Uh, it becomes atrophic. Uh, it can reduce by half or even more than that, and because it's destroyed, the production is no longer there, and the levels of thyroid hormone in the circulation will reduce. It's exactly the opposite of hyperthyroidism, will come down, and the tissues now will be missing thyroid hormone. Where is the hormone that comes here, and they don't have that. The interesting thing about hypothyroidism is that when a patient has heart failure, we make the diagno- we try to treat the heart, right? We give drugs to make the heart pump more blood, you know, reduce, uh, peripheral resistance. We wanna help that heart to work. We, we don't do that for the thyroid. We just forget about the thyroid. We don't say, "Oh, let's give an au- immune de- treatment. Let's..." No, no, no. It became so easy to think, "Let's replace the hormone and let the thyroid die." So that the treatment of hypothyroidism is through replacement therapy, it's called. So we think, "Let's just give the body the hormone that the thyroid was producing."

    13. PAPeter Attia1:04:21

        And the implication of that, Tony, which is unstated but must be correct, is that the same autoimmune condition that is ravaging the thyroid is doing nothing else anywhere else in the body that is counterproductive. In other words, to believe that replacing the hormone that is being lost through the immune system's attack on the thyroid gland, you have to believe that nothing else is being injured.

    14. ABAntonio Bianco1:04:49

        Right, but that's not actually correct.

    15. PAPeter Attia1:04:51

        It's not.

    16. ABAntonio Bianco1:04:52

        No.

    17. PAPeter Attia1:04:52

        Interesting.

    18. ABAntonio Bianco1:04:52

        We, uh, we evolved.

    19. PAPeter Attia1:04:54

        Okay.

    20. ABAntonio Bianco1:04:54

        Exactly. We- we're thinking like that, but then you start thinking, "Well, wait a minute." I'll give you an example. A perfectly healthy woman with a healthy thyroid becomes pregnant, and as a screening, we're gonna detect the antibo- the TPO antibody, the one that destroys the thyroid, and, uh, finding, okay, she has positive antibodies, T- TPO positive, even though her thyroid is normal, but she's pregnant and she has positive TPO. We know that if you have positive anti P- TPO and you're pregnant, your chances of having a miscarriage increase. Your chances of-

    21. PAPeter Attia1:05:36

        How much?

    22. ABAntonio Bianco1:05:38

        Hmm. I, I, I would, I think that a different series w- will have different numbers, but it's not insignificant, okay? I, I will have to get back to you on the, on how much is increased, but, and there's also increased chance of prematurity just because the TPO posi- antibody is positive.

    23. PAPeter Attia1:05:58

        Even without rise in TSH?

    24. ABAntonio Bianco1:06:00

        Without hypothyroidism. Exactly. So that in itself is a demonstration that-

    25. PAPeter Attia1:06:06

        Something else is going on

    26. ABAntonio Bianco1:06:07

        ... either the TPO is doing something on its own or, uh, its, uh, i- its presence is associated with something else that we don't know. So it happens that autoimmune diseases, they, they might come together with other autoimmune diseases.

    27. PAPeter Attia1:06:25

        And, and of course, in that situation, when you state it that way, it seems far more likely that it's the second of those two scenarios. The very same immune system that is now attacking the thyroid, which we can detect through the TPO, is also attacking the fetus.

    28. ABAntonio Bianco1:06:42

        Exactly. It's doing something else, or the-

    29. PAPeter Attia1:06:44

        Because the fetus is foreign

    30. ABAntonio Bianco1:06:45

        ... or the placenta-
11. 1:09:34 – 1:20:58

    More on hypothyroidism: diagnostic biomarkers, antibody patterns, & non-autoimmune presentations

    1. PAPeter Attia1:09:34

       to have that insane curiosity.

    2. ABAntonio Bianco1:09:35

       I have to tell you, it took me twenty years to get there, but it did happen to me as well. Uh, and, you know, I can tell the story why I became interested in hypothyroidism. It's exactly because I had a patient that told me, "I'm, I'm a teacher. I lost my job because I became hypothyroid." And I said, "Why?" "Well," but I, I looked at the TSH was normal, free T4 was normal. "So you're..." "Uh, no," she said, "I cannot teach anymore. I became-- I had brain fog. I became unfocused. I don't have that energy. I quit." I said, you know... I said what I told all my patients that presented with that scenario, "You may, you may need to do therapy, psychotherapy." And she start crying, and she goes home unhappy. Two weeks later, I saw another teacher that came and told me, "I lost my job because I became hypothyroid." And I, I said, "No, this cannot be coincidence." So they both had high-functioning jobs. They have to, you know, taking care of kids, high school kids, math teachers, or... So, and the hypothyroidism, uh, it, it made it not possible for them to continue with their jobs. I went to my lab, and I changed what I was doing. I refocused my research.

    3. PAPeter Attia1:10:55

       But that's amazing because I don't think you could be faulted for saying, "Wait a minute. They have a normal TSH. They have normal free T3, free T4. All their biometric stuff is normal. There could be many reasons why they're having a hard time focusing." What gave you the confidence to drop what you were doing and go and pursue that? I mean, that's a bold step.

    4. ABAntonio Bianco1:11:18

       Well, they both were-- that both was triggered by hypothyroidism. They were functioning perfectly normal before they had hypothyroidism, and one of them had surgery. She said, "The day I had surgery, I left the hospital taking levothyroxine. I could not... My brain did not work anymore."

    5. PAPeter Attia1:11:37

       Oh, I see, I see. So there was a fundamental change in her.

    6. ABAntonio Bianco1:11:39

       Absolutely.

    7. PAPeter Attia1:11:39

       Okay, got it, got it.

    8. ABAntonio Bianco1:11:40

       And so they both had this change.

    9. PAPeter Attia1:11:42

       I see.

    10. ABAntonio Bianco1:11:42

        So the only thing that changed was-

    11. PAPeter Attia1:11:44

        Was they both had their thyroids removed-

    12. ABAntonio Bianco1:11:45

        And they were-- Right, and they were-

    13. PAPeter Attia1:11:46

        But it wasn't being replaced correctly

    14. ABAntonio Bianco1:11:47

        ... they were other well, otherwise healthy-

    15. PAPeter Attia1:11:50

        Yep. Got it

    16. ABAntonio Bianco1:11:51

        ... young, uh, you know, middle-aged women. So really, uh, for me, uh, what you described with your mentor, exactly the same thing happened. I refocused my research, uh, you know, carefully because I knew I was going into an, a controversial area and, uh, trying to understand what was happening with those patients.

    17. PAPeter Attia1:12:13

        Going back to hypothyroidism, um, just from a semantic perspective, autoimmune thyroiditis involves anything that is hyperthyroid, or can that be hypo as well? Does the, does the term-- So Hashimoto's is an autoimmune-

    18. ABAntonio Bianco1:12:31

        Hypothyroid. The Hashimoto's is the prototypical hypothyroidism.

    19. PAPeter Attia1:12:35

        Are there non-Hashimoto's autoimmune conditions that decrease thyroid as well?

    20. ABAntonio Bianco1:12:40

        Yes. We don't have a name for them.

    21. PAPeter Attia1:12:41

        Okay, got it.

    22. ABAntonio Bianco1:12:42

        However, there's all sorts of, uh, you know, different, uh, uh, for example, uh- A subacute thyroiditis. Uh, we don't know exactly how it happens. Patient develop a huge inflammation of the thyroid with very painful... And you make the diagnosis, you tr- you try to feel the thyroid gland, you're moving towards the patient, the patient is moving [chuckles] far away from you because the neck is so painful. And you, you basically don't need to put your hands there-

    23. PAPeter Attia1:13:10

        You don't need to touch them

    24. ABAntonio Bianco1:13:11

        ... because you already know the diagnosis. So that is clearly there's some, some autoimmunity going on or inflammation or- of the thyroid, and that destroys the thyroid very rapidly in most cases. But there are multiple forms. W- uh, the only one we have a name for is Hashimoto's because it, it identified the TPO antibody. There are other forms of antibodies.

    25. PAPeter Attia1:13:34

        Yeah. What are the other antibodies that we typically look at here besides, uh, TPO?

    26. ABAntonio Bianco1:13:39

        TPO is the most important one. There's another one that's antithyroglobulin-

    27. PAPeter Attia1:13:42

        Mm-hmm

    28. ABAntonio Bianco1:13:43

        ... which is also, uh, specific. Thyroglobulin is a protein that's only produced in the thyroid, and TPO also, it's against the peroxidase that's only produced in the thyroid. So these two antibodies are very specific. The antithyroglobulin is less important. Um, it's, it, it's not... It can be increased in Graves' disease, for example. The TPO is generally-

    29. PAPeter Attia1:14:06

        TPO is the main one

    30. ABAntonio Bianco1:14:07

        ... it's more... Yes.
12. 1:20:58 – 1:35:35

    Thyroid hormone replacement therapy

    1. PAPeter Attia1:20:59

       let's now talk about the thyroid replacement strategies.

    2. ABAntonio Bianco1:21:04

       Mm-hmm.

    3. PAPeter Attia1:21:04

       Um, I guess before we leave that, I do wanna kind of close the door on something, which is, what-- are there any clinical trials that are going on examining the use of steroids to try to eradicate what's happening in Hashimoto's first, as a first and foremost attempt, even during that honeymoon phase before the thyroid gets destroyed? Or is that not being looked at and it's still primarily accepted that we're just going to replace the thyroid hormone?

    4. ABAntonio Bianco1:21:36

       I think so. I mean, I, I don't know. I'm not aware of anything, and I had never heard that this has been tried.

    5. PAPeter Attia1:21:41

       Okay. So let's now talk about therapy. Um, there are two, I believe, two FDA-approved therapies for, uh, thyro- exogenous replacement of the thyroid hormone.

    6. ABAntonio Bianco1:21:56

       Mm-hmm.

    7. PAPeter Attia1:21:57

       There is an FDA-approved molecule for T4 and an FDA-approved molecule for T3.

    8. ABAntonio Bianco1:22:03

       Correct.

    9. PAPeter Attia1:22:04

       Um, the branded name for the T4 is Synthroid. Uh, but of-

    10. ABAntonio Bianco1:22:11

        One of them

    11. PAPeter Attia1:22:12

        ... one, one of them. There are many brands?

    12. ABAntonio Bianco1:22:13

        Yes.

    13. PAPeter Attia1:22:14

        Yeah. Okay, got it. I thought the rest were all sort of generic, but-

    14. ABAntonio Bianco1:22:17

        Mm

    15. PAPeter Attia1:22:17

        ... point is there are... So there are many formulations that are T4, many formulations that are T3.

    16. ABAntonio Bianco1:22:22

        Correct.

    17. PAPeter Attia1:22:23

        Um, and is it safe to say that today more physicians that would stick with only FDA-approved treatments would favor T4 monotherapy and that T3 has somewhat fallen out of favor? Or what is the current state of that?

    18. ABAntonio Bianco1:22:44

        T3 was never considered as standard of care for treatment of hypothyroidism. Uh, T4 is the standard of care. Levothyroxine is the standard of care. T3 has been approved, uh, first because it was discovered in 1952. Someone patent and they got, uh... They didn't know exactly when they treat it.

    19. PAPeter Attia1:23:03

        Mm.

    20. ABAntonio Bianco1:23:04

        So they, they work with the FDA and, uh, got approval. And it's mostly used, or used to be used, in patients that had thyroid cancer and that, uh, we didn't have, uh, TS- exogenous TSH to stimulate the thyroid gland. So we would withdraw levothyroxine, and during a couple of weeks, we would put patients on liothyronine, on T3, uh, just as part of the, the t- the-

    21. PAPeter Attia1:23:33

        The bridge

    22. ABAntonio Bianco1:23:33

        ... the diagnostic... Exactly. To hypothyroidism, you would look for cancer, uh, spread through the body. As, as treatment of hypothyroidism only, uh, no guidelines recommend use of, uh, liothyronine or T3, uh, a-as a standalone. Although I have to say, I've seen significant number of patients that have convinced their doctors that they can only take T3 as a treatment for hypothyroidism. And it's-- maybe I have seen, uh, in a number of years, maybe 10 patients, maybe 20 patients, that they come and they said, "This is what I take. I take T3, and my body doesn't take T4, doesn't accept T4, and this is how I feel, and please help me maintain this." And so they exist. We don't know why they feel like that, uh, but it's extremely rare that someone will be treated with T3 monotherapy. It's certainly not recommended to do that.

    23. PAPeter Attia1:24:38

        And part of the challenge with T3 monotherapy is that T3 has a short half-life-

    24. ABAntonio Bianco1:24:45

        That's correct

    25. PAPeter Attia1:24:46

        ... and therefore, um, when you take it, it really shows up. You get a real burst of energy and all of the both positive and negative side effects of T3.

    26. ABAntonio Bianco1:24:56

        Correct.

    27. PAPeter Attia1:24:57

        And then, of course, you're chasing it, and you have to figure out how to give it At regular enough doses, but then of course you can't be giving it too late in the day because then-

    28. ABAntonio Bianco1:25:05

        Right

    29. PAPeter Attia1:25:05

        ... it will impact sleep. Whereas to your point, T4 has a very long half-life.

    30. ABAntonio Bianco1:25:10

        That's correct.
13. 1:35:35 – 1:43:25

    More on thyroid replacement strategies: exploring the evidence gaps, mortality signals, effects on lipids

    1. PAPeter Attia1:35:35

       one because it, it raises a question, right? Which is, is this two and, two and a half fold increase in mortality-

    2. ABAntonio Bianco1:35:45

       Mm-hmm

    3. PAPeter Attia1:35:45

       ... because of Synthroid? Is it do... Is it, does it have some off-target effect? Presumably-

    4. ABAntonio Bianco1:35:54

       Mm-hmm

    5. PAPeter Attia1:35:54

       ... it drives up sympathetic tone that leads to-

    6. ABAntonio Bianco1:35:57

       Mm-hmm

    7. PAPeter Attia1:35:57

       ... more adverse cardiac outcomes or something of that nature.

    8. ABAntonio Bianco1:35:59

       Mm-hmm.

    9. PAPeter Attia1:36:00

       Or is it that if you have hypothyroidism, you are very likely-

    10. ABAntonio Bianco1:36:05

        That's exactly right. Yes

    11. PAPeter Attia1:36:05

        ... to have something else that is driving up your mortality? And by the way, if left untreated, i- i.e. if you were not taking the thyroid replacement, the mortality difference could be 5X.

    12. ABAntonio Bianco1:36:17

        Oh, ab- absolutely.

    13. PAPeter Attia1:36:17

        The causality is everything-

    14. ABAntonio Bianco1:36:19

        Oh, no

    15. PAPeter Attia1:36:19

        ... in this question.

    16. ABAntonio Bianco1:36:19

        Absolutely. Yes. So let's address that. It's for sure there are other comorbidities to the hypothyroidism that are causing, that, that are contributing to the increased mortality, other autoimmune diseases that we're not even diagnosing-

    17. PAPeter Attia1:36:34

        Mm

    18. ABAntonio Bianco1:36:34

        ... but, and patients have. Absolutely. I agree with that. Now, I don't think levothyroxine is doing anything bad. I think that it's restoring euthyroidism in a incomplete fashion, because what are these patients dying of in this study?

    19. PAPeter Attia1:36:52

        Yeah.

    20. ABAntonio Bianco1:36:52

        We know that they die of cardiometabolic diseases. They have increased cholesterol. Uh, so the number one co-medication that is prescribed with levothyroxine is-

    21. PAPeter Attia1:37:03

        Statin

    22. ABAntonio Bianco1:37:03

        ... statin. So we are not restoring... As you know, cholesterol goes up in patients with hypothyroidism.

    23. PAPeter Attia1:37:10

        Yep.

    24. ABAntonio Bianco1:37:10

        But does it go back to normal after, uh, the TSH has been normalized? Answer, no. We have to give statin to ensure that the cholesterol remains. So that tells you that the liver, in my... That's, again, I don't have a proof of that because I cannot do a biopsy. In a rat, yes, the liver remains hypothyroid in a T- in a rat with normal TSH treated with levothyroxine.

    25. PAPeter Attia1:37:35

        Let, let me make sure I'm restating this because that's a very important point.

    26. ABAntonio Bianco1:37:38

        Right.

    27. PAPeter Attia1:37:38

        And we actually didn't... You and I didn't discuss this earlier, but we, we sort of took it for granted. It's worth pointing out that in the hypothyroid state, the liver cannot clear LDL effectively.

    28. ABAntonio Bianco1:37:50

        Correct.

    29. PAPeter Attia1:37:51

        So even though this isn't on the top five list of things that doctors worry about or patients worry about, when you are hypothyroid, you are going to have an elevated LDL cholesterol and ApoB-

    30. ABAntonio Bianco1:38:02

        Correct
14. 1:43:25 – 1:52:11

    Hypothyroidism basics: causes, antibody implications (including pregnancy), & how to make the diagnosis before choosing therapy

    1. PAPeter Attia1:43:25

       of this pendulum, right?

    2. ABAntonio Bianco1:43:26

       Yep.

    3. PAPeter Attia1:43:26

       Which is there's another school of thought in this, in this idea of what, what I guess sometimes gets referred to as functional medicine. Uh, it's a term I don't actually understand-

    4. ABAntonio Bianco1:43:36

       Mm-hmm

    5. PAPeter Attia1:43:36

       ... because I don't know what the alternative is, which might be dysfunctional-

    6. ABAntonio Bianco1:43:39

       Yeah

    7. PAPeter Attia1:43:40

       ... medicine. But, um- In the, in the sort of schools of functional medicine, it does seem that when I talk to individuals of this stripe, very often everybody has hypothyroidism and, um, I'm being a little facetious, but not really.

    8. ABAntonio Bianco1:43:56

       Yep, yep.

    9. PAPeter Attia1:43:57

       So, so help me understand that point of view, which is one could listen to what you're saying and s- and say, "Wow, you've really made the case for how we can't miss this diagnosis."

    10. ABAntonio Bianco1:44:07

        Mm-hmm.

    11. PAPeter Attia1:44:08

        Um, we, we should just m- make sure that every single person doesn't have hypothyroidism, even if they're biochemically normal-

    12. ABAntonio Bianco1:44:18

        Mm-hmm

    13. PAPeter Attia1:44:18

        ... and even if their symptoms are kind of vague and could belong to something else.

    14. ABAntonio Bianco1:44:22

        Mm-hmm.

    15. PAPeter Attia1:44:23

        So how do we, how do we make sense of the other side of this?

    16. ABAntonio Bianco1:44:27

        Okay. Let's-- Now we're talking about diagnosis. It's very important because what's, what's true for diagnosis, it's not true for treatment when we assess the thyroid function. So when you are assessing the thyroid function for, in doing diagnosis, you, you... Normally we measure TSH and free T4. Again, TSH is extremely sensitive, free T4 is sensitive, and T3, there's no role in the diagnosis of hypothyroidism because T3 is going to be normal. I can guarantee you that. Uh, T-- Unless the patient does not have a thyroid or is an overt case of hypothyroidism, in, in a TSH 10, TSH, T3 is gonna be normal because the, the system evolved to defend itself against iodine deficiency. So when it's ch- when the system is challenged, it, it does everything possible to maintain T3 normal. So, uh, elevates TSH, free T4 comes down. In the beginning of hypothyroidism, T3 is normal. It's the same thing that happens when we d- deprive someone from iodine. The beginning TSH starts to go up, T4s go down, T3 is normal. So T3 has no role in di- diagnosis of hypothyroidism. Free T4 and TSH do. Now, patients will come with a normal free T4, a normal TSH, and say, "I'm hypothyroid because I feel tired. I have all the symptoms. I looked it up. I have all the symptoms of hypothyroidism. I, I-- My body temperature is low. I gain weight. My hair is falling. I'm very tired. My periods are altered. I don't have energy to do anything." These are all symptoms of hypothyroidism. And then you say, "Well, but your thyroid function, I'm looking here, is perfectly normal." "I have secondary hypothyroidism. My TSH doesn't go up. That's what I have." Now, secondary hypothyroidism-

    17. PAPeter Attia1:46:39

        Secondary thy- hypothyroidism-

    18. ABAntonio Bianco1:46:41

        ... is when the pituitary gland cannot produce-

    19. PAPeter Attia1:46:43

        Cannot respond to-

    20. ABAntonio Bianco1:46:44

        That's right

    21. PAPeter Attia1:46:44

        ... TRH

    22. ABAntonio Bianco1:46:45

        ... or the hypothalamus or the TSH-

    23. PAPeter Attia1:46:46

        Yep

    24. ABAntonio Bianco1:46:46

        ... is not working. So, uh, it, it, it's a real entity, clinical entity, the secondary hypothyroidism. Very rare. It's not common. It's very rare. Less than 1% of the cases of hypothyroidism have, uh, are secondary hypothyroidism. And, but the important thing is the free T4 in these patients must be below normal because otherwise you don't have hypothyroidism. You know, to, to have secondary hypothyroidism, you have hypo- you need to have hypothyroidism, which is the hallmark of hypothyroidism. There's a free T4 that's below normal with a TSH that doesn't go up. Okay. If you have a low T4 or low free T4 and a T- a normal TSH, okay, forget about TSH. Probably you do have secondary hypothyroidism, and I would wanna do some imaging studies of your pituitary gland or hypothalamus to make sure everything is okay, you don't have a tumor or anything like that. But, but you do have to have a free T4 that's below normal. Uh, patients... But most patients-

    25. PAPeter Attia1:47:55

        So sorry, the one distinguishing feature for secondary hypothyroidism, they're gonna have a normal TSH, they're gonna have normal antibodies-

    26. ABAntonio Bianco1:48:02

        Yes

    27. PAPeter Attia1:48:02

        ... they're gonna have symptoms, but they need to have low free T4.

    28. ABAntonio Bianco1:48:05

        That's correct. Absolutely. Because otherwise, your thyroid is working well. If you have a normal free T4, you have a normal thyroid, uh, from a functional point of view. Now, how about the symptoms? What's the weight that we put on-

    29. PAPeter Attia1:48:20

        Yeah

    30. ABAntonio Bianco1:48:20

        ... uh, all these symptoms? Do they-- D- don't they count for anything? Unfortunately, all symptoms of hypothyroidism are not pathognomonic, meaning they're not specific for hypothyroid. They can be caused by anything, by other disease, by comorbidities, anemia, iron deficiency, um, obesity. Menopausal syndrome is the number one confounding factor of... You cannot distinguish menopausal symptoms s- uh, of from hypothyroidism. It's really so much that, you know, in, in my clinic, I always ask for TSH and FSH for these kinds of patients because I wanna know how is the ovary working, because the symptoms are not distinguishable. Many patients measure the temperature. There's a lot of, uh... It's very popular, uh, uh, functional medicine doctors will recommend measuring temperature in the morning. Uh, it, it is true that patients with hypothyroidism have lower temperature. What's not true is if you have a slightly lower tempera- you don't have hy- it doesn't mean you have hypothyroidism. So all these clinical indicators, uh, much to the frustration of many patients, are really not relevant when it, when they compare with TSH and free T4. You really need to rely on TSH and free T4. Because studies that relied on, on, on those symptoms just show that you cannot distinguish. That they have done double-blinded studies just based on symptoms. You cannot tell who has hypothyroid and who doesn't.
15. 1:52:11 – 2:05:26

    Thyroid medication: compounded controlled-release T3, brand name versus generic, & what Antonio prescribes to newly diagnosed hypothyroid patients

    1. PAPeter Attia1:52:11

       So the one therapeutic option we still have not addressed, which is an extension of what we've talked about, is the compounding of control release T3.

    2. ABAntonio Bianco1:52:21

       Mm-hmm.

    3. PAPeter Attia1:52:22

       So what, what is the, um... And, and, and again, there's a... You're opening another can of worms here when we get into compounding because you have compounding pharmacies that are very reputable and do very good work-

    4. ABAntonio Bianco1:52:33

       Correct

    5. PAPeter Attia1:52:33

       ... and have FDA certificates-

    6. ABAntonio Bianco1:52:34

       That's exactly right

    7. PAPeter Attia1:52:35

       ... for everything they put in.

    8. ABAntonio Bianco1:52:35

       Yeah, I was gonna say that.

    9. PAPeter Attia1:52:36

       And then you have compounding pharmacies that you wouldn't let make medications for your pets-

    10. ABAntonio Bianco1:52:41

        Correct

    11. PAPeter Attia1:52:41

        ... if you saw how unregulated they were, and they're the absolute scum of the earth. So let's only discuss this through the lens of good compounding pharmacies-

    12. ABAntonio Bianco1:52:52

        Mm-hmm

    13. PAPeter Attia1:52:52

        ... which we've done a whole podcast on this topic-

    14. ABAntonio Bianco1:52:54

        Mm-hmm

    15. PAPeter Attia1:52:54

        ... for people that we'll link to in the show notes-

    16. ABAntonio Bianco1:52:56

        Mm-hmm

    17. PAPeter Attia1:52:56

        ... if you wanna know if you're dealing with a reputable compounding pharmacy or not. Um, so, so if you're dealing with a reputable compounding pharmacy, what is your view of the control release T3, which is often given as an adjunct to people taking T4?

    18. ABAntonio Bianco1:53:12

        Mm-hmm. Uh, there's no scientific basis for the control release. There's not a single paper in w- in which a compounded product that was made in a pharmacy, uh, exhibited a slow release profile.

    19. PAPeter Attia1:53:28

        So you, you're telling me no one's ever run the pharmacokinetics of the control release product?

    20. ABAntonio Bianco1:53:33

        There are some studies... There's one study in which a companies claimed they had a slow release, and they, they did-- Someone did the study, and it was proven to be identical to the T3, normal T3. So we don't have a publication that says, "This is the slow release T3. Oh, it works perfectly." No, it doesn't exist.

    21. PAPeter Attia1:53:56

        I mean, this is mind-boggling to me-

    22. ABAntonio Bianco1:53:58

        This is all claimed. This is claimed, but-

    23. PAPeter Attia1:53:59

        ... given how simple this is to test.

    24. ABAntonio Bianco1:54:01

        Right.

    25. PAPeter Attia1:54:02

        Now, one thing I will say, and this could be the power of suggestion, I've seen many patients who can't tolerate more than five micrograms of Cytomel-

    26. ABAntonio Bianco1:54:13

        Right

    27. PAPeter Attia1:54:13

        ... which is the immediate release-

    28. ABAntonio Bianco1:54:15

        Yep

    29. PAPeter Attia1:54:15

        ... T3, but they can easily take 15 micrograms of a control release T3.

    30. ABAntonio Bianco1:54:21

        That... Interesting.
16. 2:05:26 – 2:08:22

    Redefining treatment success: why normalizing TSH isn’t always enough for patients with hypothyroidism

    1. PAPeter Attia2:05:26

       So that defines the therapy. So now the goal of therapy is what? What are you targeting-

    2. ABAntonio Bianco2:05:35

       Mm-hmm

    3. PAPeter Attia2:05:35

       ... to tell you we have now reached the correct dose?

    4. ABAntonio Bianco2:05:39

       I, I think that's a, a phenomenal question. If you ask the guidelines that are put together by the, the, the professional societies, uh, it's to normalize TSH. That's the goal of the therapy.

    5. PAPeter Attia2:05:52

       Independent of free T4?

    6. ABAntonio Bianco2:05:53

       No, or t-to normalize free T4, because free T4 is usually is gonna be even, uh, in many cases above normal. But, uh, you'd have to normalize TSH and free T4. You pay less attention to symptoms. And I-- So the goal of the therapy is to achieve biochemical euthyroidism. It's not to achieve clinical euthyroidism. And why do we say that? Because we know we cannot achieve euthyroid, clinical euthyroidism in all patients. We can't. So just the goal-- to make it easier for the doctor to, to provide some rationale for the doctor, just normalize TSH. But I argue that if the patient continues to exhibit symptoms, we did not achieve an ideal therapy. I mean, it, it-- And, and this is not unheard of, right? Depression. What is the antidepressant that-

    7. PAPeter Attia2:06:46

       Well, of course, we don't have a biomarker, so we can't.

    8. ABAntonio Bianco2:06:49

       Well, the biomarker we use, we use TSH, right? For hyp-

    9. PAPeter Attia2:06:52

       No, no, but I'm saying we don't have a biomarker for depression.

    10. ABAntonio Bianco2:06:55

        Oh, absolutely. But, you know, w-what is the, the antidepressant medication that cures a hundred percent of the patient? None.

    11. PAPeter Attia2:07:02

        Yeah.

    12. ABAntonio Bianco2:07:02

        Zero. So I think it's, it, it's, it would be easier if we started to, to take an unbiased approach and say, "Okay, this treatment works well for most patients, super fine. Let's consider hypothyroidism as a risk factor for cardiometabolic disease, and let's focus on the other patients that we can't resolve, and let's try to fix that." Most guidelines have migrated to that position, recognizing, number one, that levothyroxine is not eff-eff, uh, efficient for all patients. That's already a major change because we were t-- I was told patients that are not feeling well, you should send them to psychotherapy. So we moved from that position to saying levothyroxine is an incomplete treatment for those patients. We might wanna try combination therapy, and combination therapy is either synthetic or desiccated thyroid extract.

    13. PAPeter Attia2:08:05

        So what about the scenario where you fix the free T4 The symptoms are fine.

    14. ABAntonio Bianco2:08:13

        Mm-hmm.

    15. PAPeter Attia2:08:13

        The TSH is still markedly elevated.

    16. ABAntonio Bianco2:08:15

        Mm-hmm.

    17. PAPeter Attia2:08:15

        What do you do there?

    18. ABAntonio Bianco2:08:17

        Uh, t-t-- let's think about why would that be.

17. 2:08:22 – 2:18:45

    Case studies: analysis of two unusual cases of thyroid disease

    1. PAPeter Attia2:08:22

       I have a case study, an actual patient.

    2. ABAntonio Bianco2:08:24

       Yeah.

    3. PAPeter Attia2:08:25

       I wanna, I wanna walk this, this case through you.

    4. ABAntonio Bianco2:08:27

       Okay.

    5. PAPeter Attia2:08:27

       Okay. So there's a patient, [clears throat] uh, in his early 50s, very healthy, no i-- no, no health issues at all. Um, presents with a TSH. This is his first presentation to us. So we met him, and his TSH was seventy-four point seven.

    6. ABAntonio Bianco2:08:47

       Okay.

    7. PAPeter Attia2:08:48

       Um, and that was, uh, four or five, four years ago.

    8. ABAntonio Bianco2:08:53

       How about the free T4?

    9. PAPeter Attia2:08:55

       Uh, I don't have it in front of me. I believe it was low normal. Uh, so w- w- w-- point seven? Does that sound about right? Point seven, point eight-ish?

    10. ABAntonio Bianco2:09:05

        Yeah. I think the, the... Depends on the assay.

    11. PAPeter Attia2:09:07

        Yeah.

    12. ABAntonio Bianco2:09:08

        It, it's around a lower limit of normal. Yeah.

    13. PAPeter Attia2:09:10

        Yep. That, that was my recollection. Um, [clears throat] put him on T4, and within six months, his TSH is twenty-three point seven. Um, but he is complaining of symptoms of hyperthyroidism. We go through four years of, or y- yeah, basically four years of constant changing everything. We move to straight desiccated.

    14. ABAntonio Bianco2:09:46

        Mm-hmm.

    15. PAPeter Attia2:09:46

        We move to combination synthetic, uh, control release, you name it. We basically are at a point where [clears throat] TSH, most recently thirteen point three, free T4 point eight six, free T3, which I think we're not gonna be terribly excited about, three point six. But we-- bottom line is, we can't get that TSH-

    16. ABAntonio Bianco2:10:19

        Mm-hmm

    17. PAPeter Attia2:10:19

        ... normal without him exhibiting all sorts of subjective-

    18. ABAntonio Bianco2:10:23

        Mm-hmm

    19. PAPeter Attia2:10:23

        ... signs of hypothyroidism. So do we just accept that his TSH is going to have to be elevated as long as his symptoms are okay and his T4 is in the lower limit of normal?

    20. ABAntonio Bianco2:10:37

        Let, let, let me ask a couple more questions. Uh, did he have a, a goiter?

    21. PAPeter Attia2:10:42

        No.

    22. ABAntonio Bianco2:10:42

        No goiter. Okay. Did he ever have a normal TSH?

    23. PAPeter Attia2:10:47

        Yes. He has had-

    24. ABAntonio Bianco2:10:48

        If-

    25. PAPeter Attia2:10:48

        ... a history of a normal TSH as an adult.

    26. ABAntonio Bianco2:10:49

        Oh, he had a history of normal?

    27. PAPeter Attia2:10:50

        Yes. Yeah.

    28. ABAntonio Bianco2:10:51

        Because that's really important.

    29. PAPeter Attia2:10:52

        Yes.

    30. ABAntonio Bianco2:10:52

        So it's not a genetic-
18. 2:18:45 – 2:23:09

    Dangers of supplementing with high levels of iodine, & female-specific risk of thyroid disease

    1. PAPeter Attia2:18:45

       question, but I wonder how often it presents, is there are people out there that are supplementing iodine at very high levels.

    2. ABAntonio Bianco2:18:53

       Right.

    3. PAPeter Attia2:18:53

       So you not-- you, you mentioned earlier that, look, if you eat even a modest amount of seafood and use table salt, you're, you're gonna get iodine.

    4. ABAntonio Bianco2:18:59

       You're fine. Yep.

    5. PAPeter Attia2:19:00

       Um, but you know, there's some people out there who think you should never use table salt. You should only use some special non-

    6. ABAntonio Bianco2:19:06

       Himalayan. Yeah

    7. PAPeter Attia2:19:07

       ... Himalayan non-iodized salt. Um, and-- or, or that you need to supplement with enormous amounts of iodine. Uh, what is the risk of high-dose iodine supplementation?

    8. ABAntonio Bianco2:19:20

       Autoimmune thyroid disease. Uh, we know in Japan... For example, the daily, uh, iodine intake should be around a hundred and fifty micrograms for adults. For, for pregnant women, we should have about two hundred and fifty micrograms. It's because you're, you're expanding, uh, your pool, so you need a little bit more. But, uh, in Japan, their normal amount of i- the, the, you know, the-- in their normal diet, it will give them about five hundred to six hundred micrograms of iodine per day, and as a result, they have increased, uh, uh, incidence of, uh, autoimmune thyroid disease. So we know that the excess of iodine is going to mess up with the thyroid, and, uh, it will cause increased antigenicity of the thyroid and trigger autoimmune disease.

    9. PAPeter Attia2:20:10

       And it will be an autoimmune hypo.

    10. ABAntonio Bianco2:20:12

        That's correct.

    11. PAPeter Attia2:20:13

        Okay.

    12. ABAntonio Bianco2:20:14

        Uh, that's correct. Unless Uh, uh, let's just-- You know, it's, it's difficult on this podcast because, uh, you know, I'm talking to the general public, but I'm, I'm sure some doctors will be listening, and then we have to-

    13. PAPeter Attia2:20:29

        Our, half of our audience is actually twenty to twenty-five percent physicians.

    14. ABAntonio Bianco2:20:32

        Oh, that's great. So-

    15. PAPeter Attia2:20:33

        Many doctors are listening.

    16. ABAntonio Bianco2:20:34

        So we, we have to think about iodine-induced hyperthyroidism. Sometimes you have a nodule in the thyroid-

    17. PAPeter Attia2:20:41

        And this basically provides substrate

    18. ABAntonio Bianco2:20:43

        ... it's silent. Exactly. It's silent, and then when you inc- start taking pills of iodine, it's gonna be hyperthyroid. Then you, you-

    19. PAPeter Attia2:20:50

        Aside from the potential comorbidities, meaning, um, women, obviously perimenopausal women you mentioned might have, uh, confounding diagnoses, uh, or conditions that explain-

    20. ABAntonio Bianco2:21:05

        Mm-hmm

    21. PAPeter Attia2:21:05

        ... their hypothyroidism. Um, are there any other male-female differences that pertain to hypothyroidism? Presumably women have a slightly higher incidence, all things considered.

    22. ABAntonio Bianco2:21:17

        Oh, yeah. Ten to one.

    23. PAPeter Attia2:21:18

        Ten to one?

    24. ABAntonio Bianco2:21:19

        Oh, yeah.

    25. PAPeter Attia2:21:19

        Oh, wow.

    26. ABAntonio Bianco2:21:19

        It's gigantic.

    27. PAPeter Attia2:21:20

        I didn't know it was that big.

    28. ABAntonio Bianco2:21:20

        Oh, yeah. It's gigantic.

    29. PAPeter Attia2:21:21

        I thought it was four to one. Okay.

    30. ABAntonio Bianco2:21:22

        No.
19. 2:23:09 – 2:27:54

    Case study of a patient who presents with elevated TSH but no symptoms

    1. PAPeter Attia2:23:09

       let's kind of go back to a clinical case scenario, which is the patient who presents only with an elevated TSH. So they have normal free T4, if you define normal as within the range, but let's just say it's lower half of the range for free T4. TSH-- Oh, and n-normal antibodies and no symptoms, but TSH is eight to nine, twice the upper limit. What do you do?

    2. ABAntonio Bianco2:23:45

       How old the patient?

    3. PAPeter Attia2:23:47

       Forty years old.

    4. ABAntonio Bianco2:23:48

       Okay. So that's a case of subclinical hypothyroidism, right? Free T4 is normal. TSH is elevated. Let's find out why is the TSH elevated.

    5. PAPeter Attia2:23:57

       So let's assume we're talking about a forty-year-old male and then a forty-year-old female.

    6. ABAntonio Bianco2:24:03

       I think pr- the approach is pretty much similar. Uh, it's not normal to have an eight to nine-

    7. PAPeter Attia2:24:10

       Mm-hmm

    8. ABAntonio Bianco2:24:10

       ... uh, TSH when you have, when you're forty years old, okay? So what's going on there? This is defined as the subclinical hypothyroidism. And, uh, first we need to ask if cases in the family. Do you have-- We know there's a s- there are families that have hypothyroidism in, in, in many individuals. So, uh, we will do an ultrasound. Uh, is the thyroid showing a patchy pattern, which is typical of, uh, Hashimoto's disease, uh, or do we have a perfectly bright, normal thyroid? Uh, do we have-- Obviously, the patient has no symptoms. Uh, so what we do is first we repeat.

    9. PAPeter Attia2:24:57

       By the way, what's the range on free T4, assay range? What's normal?

    10. ABAntonio Bianco2:25:01

        Uh, I wouldn't know that.

    11. PAPeter Attia2:25:02

        But is one point one five normal?

    12. ABAntonio Bianco2:25:05

        Uh, but it depends on the lab.

    13. PAPeter Attia2:25:06

        Okay, okay.

    14. ABAntonio Bianco2:25:07

        I mean, I, I, I can't.

    15. PAPeter Attia2:25:09

        I think it's normal, but that's... Anyway, that's what his-

    16. ABAntonio Bianco2:25:12

        It sounds normal to me.

    17. PAPeter Attia2:25:13

        Yeah. That, that is his level, one point one five.

    18. ABAntonio Bianco2:25:16

        Yeah.

    19. PAPeter Attia2:25:16

        With last TSH was seven point one.

    20. ABAntonio Bianco2:25:19

        Right.

    21. PAPeter Attia2:25:19

        Uh, free T3, two point three. So that's, you know.

    22. ABAntonio Bianco2:25:24

        So, so then what, what we do is w-we determine the, the, if this is going to evolve to hypothyroidism or not. If it's d-- If we determine it's going to evolve to hypothyroidism because there's a patchy pattern, TPO is positive, the family has hypothyroidism, then we will probably be favor treatment. If we cannot find any other indication that this person is, this person is gonna develop hypothyroidism, we still, uh, there are studies showing that they will benefit from treatment with levothyroxine, especially in, in what relates to, excuse me, uh, me-metabolic disease, cholesterol, and, and other things. So [clears throat] th-there is some beneficial, uh, uh, uh- factor associated with treatment in this case. So in both cases, I would favor treatment

    23. PAPeter Attia2:26:23

        So ju-- so to, to close the loop on that, we did try him on Synthroid, and he felt worse. I, you know, I think we put him on somewhere between fifty and seventy-five micrograms just to bring his TSH down-

    24. ABAntonio Bianco2:26:37

        Mm-hmm

    25. PAPeter Attia2:26:37

        ... which we did, but he felt symptomatic.

    26. ABAntonio Bianco2:26:41

        Right.

    27. PAPeter Attia2:26:41

        So he felt better off the medication, so obviously-

    28. ABAntonio Bianco2:26:43

        Then-

    29. PAPeter Attia2:26:43

        ... we stopped the medication.

    30. ABAntonio Bianco2:26:44

        Right. Exactly.
20. 2:27:54 – 2:34:14

    How future research could reshape treatment, & Antonio’s new book

    1. ABAntonio Bianco2:27:54

       that case.

    2. PAPeter Attia2:27:54

       Wow. Okay. Tony, final topic here. Um, w- what do you want to be known? What do you want to, either personally or through the field, what do you-- what should be known within a decade that's gonna change the lives of patients, uh, dealing with, with thyroid conditions, either in the hyper or hypo state? In other words, what's our biggest blind spot today? Are we blind-- Are we deficient in our diagnostic techniques? Are we deficient in our treatment techniques? Where, where are we most lacking? Where would you like to see the most improvement in the next decade?

    3. ABAntonio Bianco2:28:27

       Well, we need to address hypothyroidism because that, there... again, twenty million individuals, patients here in the US. I think that we lack treatment. We have to improve treatment. These patients suffer a lot. I mean, we, we can't ignore that. They're vocal. We hear their stories. And, and I think we have to, uh, forget, cha-- move from the idea that we, we can't do anything but normalize TSH to try to do something. Where are we gonna evolve? I think we have to have better methods of measuring T3. Mass spec for T3 is mandatory, in my view. We should try for patients with hypothyroidism. We want to normalize T3 in the circulation, and we want to make it a reliable method, robust method. And we need-- the pharmaceutical industry needs to develop a slow-release T3.

    4. PAPeter Attia2:29:27

       Yeah.

    5. ABAntonio Bianco2:29:27

       Because, uh, to have this-- although, uh, all these studies we've done is with short-lived T3, even, even with the normal T3 standard, it's okay. It's beneficial as opposed to com- co-- to levothyroxine. But having the slow-release T3 will give that confidence to the physician that they're not doing any harm.

    6. PAPeter Attia2:29:49

       Yeah.

    7. ABAntonio Bianco2:29:49

       You're just doing what the thyroid does. That's what we need. Uh, the, the, we have not moved very fast on that. Uh, there are two approaches to slow-release T3. There's a company that developed a, a polymer of, uh, T3 that slowly breaks down in the intestine. There's another group in Italy that developed... that's treating patients with sulfate T3, which that's a very interesting strategy. Sulfate T3 is inactive, doesn't do anything. However, it's absorbed, and when it hits the liver, the liver, there's a desulfatase that works at steady state, at a steady velocity. So the liver becomes a source of T3 to the circulation. That max out at the capacity of the desulfates, desulfatase. So the liver pr- keeps secreting at a constant rate T3 as long as you give-

    8. PAPeter Attia2:30:45

       So these are both compounds that are in Europe?

    9. ABAntonio Bianco2:30:49

       One of them is in the US, is-- they're working with the FDA to have it approved.

    10. PAPeter Attia2:30:54

        I see.

    11. ABAntonio Bianco2:30:54

        The polymer. The other one is in Europe. Yes.

    12. PAPeter Attia2:30:57

        I see. So in Europe, patients can already access-

    13. ABAntonio Bianco2:31:00

        No

    14. PAPeter Attia2:31:00

        ... the time-release.

    15. ABAntonio Bianco2:31:01

        No. This is being studied.

    16. PAPeter Attia2:31:01

        It's still-- These are both... Okay, got it.

    17. ABAntonio Bianco2:31:03

        It's being studied.

    18. PAPeter Attia2:31:03

        And the one in the US, is it already in phase three?

    19. ABAntonio Bianco2:31:07

        No. They did a phase one, uh, and it was successful. They're working with the FDA to get a, a phase two, a short phase two.

    20. PAPeter Attia2:31:16

        What's gonna be the, uh, endpoint for the phase three?

    21. ABAntonio Bianco2:31:21

        I don't think... So the FDA has different pathway-

    22. PAPeter Attia2:31:24

        I guess because it's the same molecule, you go through a different pathway.

    23. ABAntonio Bianco2:31:27

        Five oh five B two. Exactly.

    24. PAPeter Attia2:31:29

        Yeah. Yeah.

    25. ABAntonio Bianco2:31:29

        It's a regulatory, a different regulatory pathway, so that luckily this will be a fast approval. Uh, but, you know, you never know what the FDA is gonna ask. So I hope it goes faster. That would be phenomenal. Either one of them, I think that these are fabulous ideas. I would like in ten years to see this available for patients.

    26. PAPeter Attia2:31:50

        That's fantastic. And then again, get the laboratories interested enough to develop a-

    27. ABAntonio Bianco2:31:55

        Absolutely

    28. PAPeter Attia2:31:55

        ... CLIA-based mass spec assay for free T3-

    29. ABAntonio Bianco2:31:58

        For T... Exactly

    30. PAPeter Attia2:31:58

        ... specifically. Okay. Great. Um, Tony, finally, you, you wrote a book, Rethinking Hypothyroidism. That's a book that, in its very title, which I-- the, the tagline is, "Why treatment must change and what patients can do," is obviously written for patients. Uh, but really, it's also a helpful book for physicians. Um, we're gonna obviously link to that. Folks should, should absolutely check that out. Um, because again, you, um, you have a very nuanced view of this, which is why I wanted to have you on the podcast.

Episode duration: 2:34:14