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大家好。
Hey, everyone.
欢迎收听《Drive》播客。
Welcome to the Drive podcast.
我是主持人彼得·阿提亚。
I'm your host, Peter Attia.
本播客、我的网站以及每周通讯都致力于将长寿科学转化为通俗易懂的内容。
This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone.
我们的目标是提供最优质的健康与保健内容，为此我们组建了一支优秀的分析师团队。
Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen.
对我而言，在不依赖付费广告的情况下提供这些内容至关重要。
It is extremely important to me to provide all of this content without relying on paid ads.
正因如此，我们的工作完全依靠会员支持才得以实现。
To do this, our work is made entirely possible by our members.
作为回报，我们为会员提供独家专属内容和远超免费用户的额外权益。
And in return, we offer exclusive member only content and benefits above and beyond what is available for free.
如果你想在这个领域的知识更上一层楼，我们的目标是确保会员获得的回报远超订阅价格。
If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription.
若想了解更多关于我们高级会员的权益，请访问peteratiamd.com/subscribe。
If you want to learn more about the benefits of our premium membership, head over to peteratiamd.com slash subscribe.
本周我的嘉宾是医生
My guest this week is Doctor.
安东尼奥·比安科。
Antonio Bianco.
安东尼奥是位医师、科学家，也是国际公认的甲状腺生理学与代谢领域专家。
Antonio is a physician, scientist, and an internationally recognized expert in thyroid physiology and metabolism.
他现任约翰·西利医学院临时高级副校长兼院长，以及德克萨斯大学医学分部首席研究官。
He is currently serving as the senior vice president and dean at Interim of the John Seeley School of Medicine and Chief Research Officer at UTMB.
他曾担任美国甲状腺协会主席。
He previously served as the president of the American Thyroid Association.
他数十年致力于研究甲状腺激素如何影响体内每个细胞，尤其专注于被称为脱碘酶的酶类——这些酶能在组织层面激活或灭活甲状腺激素。
He spent decades studying how thyroid hormones affect every cell in the body with particular focus on the enzymes called deiodinases that activate or deactivate these hormones at the tissue level.
他还是《重新思考甲状腺功能减退》一书的作者，该书探讨了甲状腺激素替代疗法背后的科学争议与患者体验。
He's also the author of Rethinking Hypothyroidism, which explores the science controversies and patient experiences surrounding thyroid hormone replacement therapy.
在本期节目中，我们将讨论甲状腺激素在全身的生成、转化及作用的基础生物学原理。
In this episode we discuss the fundamental biology of thyroid hormone production, conversion and action throughout the body.
脱碘酶如何调控局部甲状腺激素活性及其对解读检测结果的意义，仅用TSH作为甲状腺功能标志物的局限性及临床实践中常被忽视的问题，组合疗法（即T3与T4联用）对比标准左旋甲状腺素（T4）治疗。
How the deiodinase enzymes regulate local thyroid hormone activity and why that matters for interpreting lab results, the limitations of using only TSH as a marker of thyroid function and what's often missed in clinical practice, Combination therapy, that is to say T3 and T4 versus standard levothyroxine or T4 treatment.
遗传因素、组织敏感性及个体差异在甲状腺激素代谢中的作用。
The role of genetics, tissue sensitivity and individual variability around thyroid hormone metabolism.
甲状腺功能减退如何影响精力、情绪、代谢与认知功能，甲状腺激素与线粒体效率、心血管健康及长寿之间的复杂关系，为何部分患者在检测指标正常时仍感不适，以及未来研究如何重塑治疗策略。
How hypothyroidism affects energy, mood, metabolism and cognitive function, the complex relationship between thyroid hormones and mitochondrial efficiency, cardiovascular health and longevity, and why some patients continue to feel unwell despite normal thyroid labs, and how future research could reshape treatment approaches.
闲言少叙，请欣赏我与安东尼奥·比安科博士的对话。
So without further delay, please enjoy my conversation with Doctor.
安东尼奥·比安科。
Antonio Bianco.
托尼，非常感谢你专程来奥斯汀。
Tony, thank you so much for making the trip up to Austin.
我的荣幸。
My pleasure.
我想加尔维斯顿也不算太远，
I guess Galveston's not that far,
不远。
No.
三小时车程。
It's three hours.
昨晚过来还挺顺利的。
It was pretty easy last night.
所以你是那边医学院的院长。
So you're the dean of the medical school there.
你是
You're That's
还负责运营一个实验室。
running a lab.
请简单介绍一下你的研究重点，以及是什么让你对甲状腺系统研究产生兴趣的。
Tell me a little bit about what your research focuses on and maybe even what got you interested in studying the thyroid system.
嗯，我目前的研究主要是试图理解甲状腺激素的作用机制。
Well, my research right now is trying to understand what thyroid hormone does.
通过了解它在不同组织中的作用，我们将能够帮助甲状腺激素不足的患者，也就是甲状腺功能减退症患者。
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.
所以我们从组织层面入手，研究它在肝脏、心脏中的作用，然后深入到细胞层面。我们目前正在观察甲状腺激素如何影响染色质的折叠，因为这关系到它调控基因表达的方式。
So we go at the level of the tissue level, so 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, because how it does it regulates gene expression.
本质上这就是T3或甲状腺激素的作用方式——通过调控不同基因。由于基因是细胞功能的核心，调控这些基因的表达就会改变细胞的行为方式。
Basically that's how T3 or a thyroid hormone acts, by regulating different genes and because the genes are basically the essence of the cell functioning, by regulating the expression of those genes it changes the way the cell behaves.
这对整个组织、器官乃至身体都会产生重要影响。
And that has an important consequence for the whole tissue and for the organ and for the body.
那我们先从大众比较了解的甲状腺知识开始吧。
So maybe let's start with the stuff that is largely known about the thyroid.
我先说几点帮我们确定方向，当然希望你能纠正我或带我们更深入探讨。
I'll say a few things just to get us pointed in the right direction but obviously I want you to correct me and or take us into a little bit more depth.
我猜很多人都知道喉结上方有个叫做甲状腺的腺体。
I suspect many people know that they have a gland that sits over the voice box called the thyroid gland.
这大概是大多数人的认知。
That's probably what most people know.
多数人可能还知道它能分泌一种激素。
Most people also probably know that it produces a hormone.
有些人或许知道这种激素其实是无活性的，缩写为T4，因为它含有四个碘原子。
Some people might know that that hormone is actually inactive, abbreviated T4, because it has four iodines on it.
现在要说的可能就超出大众认知了——体内的酶会移除其中一个碘原子，将其转化为活性形式，我们称之为T3。
And that now we're getting maybe past what most people would know but enzymes in the body take one of those iodine off and make an active form of that hormone that we abbreviate T3.
我估计不少观众或听众都意识到这种激素非常重要，它能调节能量消耗、体温、情绪、睡眠等方方面面。
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, mood, sleep, all sorts of things.
最后我想补充一个常识性认知：有些人由于各种原因似乎无法分泌足够的这种激素，这种情况并不罕见。
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.
我们当然会详细讨论所有这些内容。
We're going to talk about all of these things, of course.
因此他们需要补充这种激素。
And that as a result of that they have to supplement that hormone.
这种情况可以被称为甲状腺功能减退症。
And that condition could be referred to as hypothyroidism.
现在有很多听众正在收听我们的节目。
And there are many people listening to us.
我敢说此刻有数以万计的听众自认为患有甲状腺功能减退症，并正在服用某种形式的甲状腺替代药物。
I would venture that there are tens of thousands of people listening to us right now that would identify as having hypothyroidism and that are taking some form of thyroid replacement.
我们今天的目标是理清这一切，因为人们对于如何替代这种激素有太多不同的看法。
Our objective today is to make sense of this whole thing because there are so many different ways that people think about how to replace that hormone.
人们对于如何诊断这种状况也有许多不同的思路。
There are so many different ways that people think about how to diagnose the condition.
与我们考虑的其他主要系统相比，这似乎是一个更为复杂的内分泌情况。
And it seems that it is a much more complex endocrine situation than the other major systems we think about.
理解睾酮水平低下似乎并不那么困难。
Doesn't seem very difficult to understand what low testosterone is.
检测方法非常简单，症状也很容易理解，补充激素也很直接。
You have a very simple assay, you understand the symptoms quite well, replacing it is quite simple.
这里的情况则大不相同。
It's very different here.
那么，话虽如此，让我们回到宏观层面，尽可能详细地讨论这个位于此处的腺体及其功能。
So, with that said, let's go back to that meta level, layer on as much detail as you'd like about this gland that sits here and what it's doing.
顺便说，刚才的介绍非常精彩。
That was a great introduction by the way.
甲状腺的功能是从血液中摄取碘，并利用这些碘来制造激素。
The thyroid gland, what it does is takes up iodine from the blood and uses that iodine to produce a hormone.
这非常有趣，也相当独特。
That's quite interesting, it's quite unique.
我们基本上每天通过饮食摄入碘，比如海鲜就富含碘。
So we basically ingest iodine every day on our diet, Seafood for example is full of iodine.
因此我们确实需要这些碘来维持甲状腺的正常功能。
So we really need that iodine so that the thyroid can function.
没有碘就没有甲状腺激素。
Without iodine there's no thyroid hormone.
幸运的是，我们会在食盐中添加碘补充。
Luckily what we do is we supplement the salt, kitchen salt with iodine.
所以只要你每天摄入合理量的碘，就无需担心，这足以生成甲状腺激素。
So this is not something that we have to worry if you have a reasonable amount of iodine every day it will be sufficient amounts to make the thyroid hormone.
甲状腺通过一系列反应捕获碘元素，最终合成甲状腺激素。
So the thyroid traps iodine and through a series of complicated reactions it centers or it makes up the thyroid hormone.
甲状腺储存着大量激素，本质上是个巨大的甲状腺激素仓库。
Now stores a large amount of hormone, the thyroid is basically a large storage of thyroid hormone.
主要是前体激素，即你提到的非活性激素T4。
Mostly the pro hormone, the inactive hormone that you mentioned T4.
T4含有四个碘原子，会缓慢释放并分泌到血液中，确保血液循环中有T4储备。
T4 again, four atoms of iodine, and then slowly releases that, secretes that T4 into the circulation on a daily basis, so that the blood has a storage of T4.
而T4本身作用不大。
Now T4 doesn't do much.
当我们讨论甲状腺激素的重要性时——它对大脑、心脏和骨骼都很重要——我们说的并不是T4。
When we talk about the importance of thyroid hormone, it's important for the brain, it's important for the heart, for the bones, we're not talking about T4.
我们说的是另一种激素，活性激素T3。
We're talking about the other hormone, the active hormone, T3.
神奇的是，只需从T4中移除一个碘原子，它就能变成完全活性的激素。
So it's amazing that by just removing one atom of iodine from the T4 it now becomes a fully active hormone.
为什么会这样呢？
And why is that?
因为细胞和组织都有受体。
Well because cells, tissues have receptors.
这些受体不喜欢T4。
The receptors don't like T4.
它们与T4的结合能力不强。
They don't bind T4 that much.
它们钟爱T3，能以高亲和力与T3结合。
They love T3, they bind T3 with high affinity.
这仅仅是构象差异还是静电作用？
This is just purely a conformational difference or is it electrostatic?
是构象差异，没错。
It's conformational, yeah.
它无法嵌入受体口袋。
It doesn't fit into the pocket.
真神奇。
Amazing.
受体口袋非常喜欢T3，但不喜欢T4。
The pocket of the receptor likes T3 a lot, it does not like T4.
它对T4的亲和力很低。
It has low affinity.
如果大量使用T4，确实会产生一些作用。
If you put a lot of T4, yes, you're gonna get some action.
但通常需要极高的浓度才能实现。
But normally those are extremely high levels.
从进化角度来看，虽然我们永远无法确定，但你是否怀疑这样设计的原因在于，分泌一种具有长半衰期的非活性前激素更有意义，它能遍布全身，然后各组织可自主决定需要多少活性激素？
And from an evolutionary perspective, not that we can ever know for sure, but do you suspect that the reason for this is that it makes more sense to secrete an inactive pro hormone that has a long half life that can go everywhere and then each tissue can selectively make its determination of how much active hormone it needs?
我认为从进化角度看，进化压力来自碘缺乏。
I think that from an evolutionary point of view, the evolutionary pressure is iodine deficiency.
因此整个系统进化出保存碘的机制。
So the whole system evolved in a way to preserve iodine.
你看甲状腺充满甲状腺激素，它含有四个碘原子，去掉一个就变成活性形式。
You see the thyroid is full of thyroid hormone, it has four atoms of iodine and then by removing one it becomes active.
所以它尽可能保存碘，而被移除的碘会怎样呢？直接回收。
So it's preserving iodine as much as possible and what happens with that iodine that was removed, right back.
它会被重新吸收。
It's taken up again.
这一切都是为了保存碘，以防我们突然陷入无法产生足够激素的缺碘状态。
So it's all about preserving the iodine so that we don't go into a moment, a situation that we don't have enough iodine to produce that hormone.
可以推测当碘充足时，你们能储备更多T4——这正是完全正确的。
And presumably when iodine is abundant, you can stockpile more T4 That's within that's the exactly right.
这很有道理。
That makes sense.
完全正确。
Exactly right.
确实非常有趣，一旦移除碘原子，分子就会变得活跃，T3被激活，但正如你所说，它的半衰期很短。
That is really interesting that once you remove the atom of iodine then what happens is that the molecule becomes active, T3 becomes active, but then it has a short half life as you mentioned.
因此对比非常鲜明，T4的半衰期约为八天，而T3的半衰期只有十二小时左右。
So the contrast is dramatic, T4 has a half life of about eight days, T3 has a half life of about twelve hours.
一旦被激活，它就会触发自身的分解。
Once it's activated it triggers its destruction.
它的作用时间短暂但效力强劲，不过它注定要被分解代谢并清除。
It has a brief action, it works potently, however it's targeted for destruction, it's just metabolized and cleared.
这说明这是身体调节甲状腺激素作用的一种方式。
And that tells you that this is a way the body has to regulate the action of thyroid hormone.
所以一旦被激活，我们要确保它在十二小时后仍然有效。
So once it's activated let's make sure it's still active twelve hours later.
你仍然需要保持所有这些活性。
You still need to have all that activity.
所以它是缓慢激活的，如果出于任何原因我们停止激活，停止后不久，T3的作用就会减弱。
So it slowly activates and if for any reason we have to stop activating, after you stop, shortly after the action of T3 will decrease.
这是一种限制组织接触活性甲状腺激素的方式。
So that's a way of limiting the amount of exposure of the tissues to the active thyroid hormone.
好的。
Okay.
那么，我接下来的问题是，我听说有不同的脱碘酶存在。
So, the next question I would have is, I've heard that there are different deiodinases.
再次说明，脱碘酶——为听众解释一下——是一种酶，顾名思义，它能从T4分子上移除一个碘原子，但还有一种分子叫做反T3。
Again, the deiodinase, just for the listener, is an enzyme that does, as its name suggests, removes an iodine atom from But T4 to there is a molecule called reverse T3.
没错。
Right.
请简单谈谈这个，以及它与T3的区别。
Say a little bit about that and how it differs from T3.
反向T3是T3的一种变体形式。
Reverse T3 is a T3, it's an alternative form of T3.
这完全取决于从T4分子中移除的是哪个碘原子。
It all depends on which iodine is removed from the molecule of T4.
T4分子有两个环，内环和外环。
The molecule of T4 has two rings, the inner ring and the outer ring.
如果从外环上去除碘原子，就会生成T3。
If you remove the iodine from the outer ring you make T3.
如果从内环上去除碘原子，就会生成反向T3。
If you remove the iodine from the inner ring you make reverse T3.
从内环还是外环去除碘原子有区别吗？不，外环上的一个不行。
Does it matter which one from the inner ring and which No, one from the outer no.
两者都不足以满足需求。
Neither one would suffice.
任选一个都能达到效果，是的。
Either one can do the trick, yes.
最奇妙的是，虽然T3是一种超级活跃的分子，但反T3却是完全无活性的。
And the amazing thing is that whereas T3 is a super active molecule, reverse T3 is dead.
它的活性甚至比T4还低。
It has less activity than T4 even.
实际上需要天文数字般的反T3剂量才能对受体产生任何作用，所以它确实没有活性。
You really need an astronomical amount of reverse T3 to do anything to the receptor so it's really not active.
现在有个有趣的现象：甲状腺不断向循环系统分泌T4，而你提到的脱碘酶会将T4转化为T3或反T3。
So that's interesting now the thyroid is constantly secreting T4 into the circulation, the deionases this enzyme that you mentioned, they will take T4 and either make T3 or reverse T3.
因此甲状腺激素要么被激活，要么被灭活。
And so either activates or inactivates thyroid hormone.
这就构成了一个可以随时改变的替代代谢途径。
And that constitutes an alternative pathway that can also be altered on a moment's notice.
突然间体内有了这么多T4，假设身体想要降低甲状腺激素的激活程度。
So all of a sudden you have all these T4 available and let's say the body wants to reduce the activation of thyroid hormone.
这时T4不会走T3代谢途径，而是优先选择反T3途径，从而完全失去活性。
Instead of putting the T4 through the T3 pathway, T4 will preferentially go through the reverse T3 pathway and will be completely inactive.
所以我打算
So I'm going
给你一个真实案例，希望你能用它向人们解释这种情况为何会发生。
to give you a true scenario and I want you to use it as an example to explain to people why that could happen.
这是个非常极端的例子。
So this is a very extreme case.
我以前经常禁食。
Now I used to do a lot of fasting.
每季度我会禁食7到10天。
So I would fast for up to seven to ten days every quarter.
过去我会在禁食前后都做血液检查。
I used to check my blood work before and after.
我会告诉你我的甲状腺数值，包括禁食开始前和结束时的典型数值。
So I'll give you my thyroid numbers, typical thyroid numbers at the beginning before I started fasting and at the end.
需要说明的是，我们还没解释TSH是什么，稍后会再讨论。
Keeping in mind we haven't explained what TSH is yet and we'll come back to it.
但先说说T3、T4部分。
But just to get the T3, T4 part.
禁食前我的TSH可能是2，游离T3是0.3，反向T3是10。
So before a fast I might have a TSH of two, a free T3 of 0.3 and a reverse T3 of 10.
禁食后TSH会升到7。
After the fast, the TSH would go to seven.
游离T3会降到0.2。
The free T3 would be 0.2.
也就是下降了50%。
So it go down by 50%.
反向T3会达到35。
The reverse T3 would be 35.
那么我体内发生了什么会导致甲状腺激素如此剧烈的变化？
So what is happening in my body that would lead to those dramatic changes in those thyroid hormones?
这是因为下丘脑——大脑中调节甲状腺功能的控制中心——检测到你没有进食。
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.
它是如何检测到的？
How does it detect that?
你的胰岛素水平偏低，瘦素水平下降，这些信号会提示下丘脑：等等，现在摄入的食物很少。
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.
甲状腺激素会加速能量消耗。
Thyroid hormone accelerates energy expenditure.
甲状腺激素的核心作用就是燃烧能量、分解糖分和蛋白质。
Thyroid hormone is all about burning energy, burning sugar, burning protein.
所以下丘脑会决定降低代谢速率——就像把脚从油门上移开——这样即使食物摄入减少（对你而言是完全断食），我们也能降低燃料燃烧的速度。
So the hypothalamus says well I have to reduce, take my food off the gas here so that even though there is less food coming in, in your case nothing, we are going to reduce the rate at which I am burning the fuel here.
因此虽然你的TSH现在处于正常范围，但这种正常是不合理的，因为你的T4水平下降了。
And so your TSH even though it is within the normal range now is inappropriately normal because your T4 came down.
你没提到T4值，但T4肯定也会随时间变化
You didn't mention your T4 but T4 for certainly would For some come time
所以TSH才会升高
and that's why the TSH went up.
对，但只是轻微上升。
Right, but slightly.
通常如果T4显著下降，TSH应该会上升更多。
Normally if you have a significant drop in T4, the TSH should go up much more.
TSH没有大幅上升是因为下丘脑在告诉TSH不要上升。
The TSH is not going up so much because the hypothalamus is telling TSH don't go up.
没必要上升，因为我们现在需要减缓代谢速度。
There's no need because right now we want to slow things down.
所以尽管T4和T3都下降了，你的TSH仍处于不恰当的正常水平。
So your TSH is inappropriately normal even though the T4 is down, the T3 is down.
为什么T3会下降？
Why is T3 down?
你的甲状腺在分泌T4的同时也会分泌少量T3，现在T3的分泌量也减少了。
Your thyroid is secreting T4 but also a little bit of T3, it's making less T3 as well.
但最重要的是我们刚提到的脱碘酶途径——现在T4会优先转化为反向T3而非T3，这就是反向T3上升的原因。
But most importantly the deiodinase pathway 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.
反向T3升高的另一个原因是，它的半衰期非常短，甚至比T3还短，只有几个小时。
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.
反向T3通过D1途径被清除。
Reverse T3 is cleared through the D1 pathway.
你提到过有三种脱碘酶。
You mentioned there are three deiodinases.
D1在清除血液循环中的反向T3方面非常重要。
The D1 is very important in clearing reverse T3 thrombo circulation.
有趣的是，D1在肝脏中大量表达，对胰岛素和碳水化合物非常敏感。
And the interesting thing is that D1 is richly expressed in the liver, very sensitive to insulin and carbohydrates.
如果你摄入大量碳水化合物，肝脏中的D1就会增加，反之则会减少。
If you are eating a lot of carbohydrates your D1 in the liver is going to go up and the opposite when you don't eat so much.
所以现在的情况是，由于你不进食，肝脏中的D1活性正在下降。
So what's happening is D1 activity is coming down in the liver because you are not eating.
胰岛素下降，碳水化合物摄入减少，而由于D1代谢反向T3，导致反向T3在血液中积累。
Insulin down, carbohydrates down, and because D1 metabolizes reverse T3, reverse T3 builds up in the blood.
因此不仅反向T3的产量增加，其代谢也在减少。
So not only there's more reverse T3 production, but there's also less reverse T3 metabolism.
这就是为什么反向T3上升，而T3下降——因为产量减少，你的能量消耗也随之降低。
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.
所以常见的情况是，人们在禁食初期会减掉大量体重，但随后会进入平台期。
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.
许多研究将这个平台期归因于甲状腺激素水平的下降。
And a lot of people, some studies attribute this plateau to the fact that the thyroid hormone levels are down.
你摄入的卡路里与能量消耗达到了平衡。
You are equating the amount of calorie you're intaking with your energy expenditure.
你在减少它。
You're reducing it.
那么有些人提到的那个比率——游离T3与反向T3的比率，这个比率的上升水平，是否可以粗略代表体内甲状腺活动的总体水平？还是说这种看法太过粗略？
And so is that ratio, which some people have talked about, the ratio 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?
如果回到我的数据，我记得初始比率是0.3，或者可以标准化为0.3比10。
So if I go back to my numbers there, I think I started out at a ratio of point three or you can normalize it but point three over 10.
可以称之为0.03或3%。
So call it 0.03 or 3%.
然后，我认为它会变成2比30。
And then, you know, I think it goes to two over 30.
我的意思是，基本上下降了50%，按数学计算，大约减少了六倍。
I mean, you know, it's basically falling by 50% of it, doing the math, like it goes down by a six fold change.
这可能意味着我的新陈代谢受到了显著抑制。
So that would maybe suggest a significant set of breaks on my metabolism.
正确。
Correct.
我们还能推断出其他信息吗？
Can we infer anything else
可以。
Yes.
我认为这个比率是脱碘酶活性的良好替代指标，因为说实话我们无法直接测量人体内的脱碘酶。
Than I think the ratio is a good surrogate of deiodinase activity because honestly we can't measure the deiodinases in humans.
我们需要进行活检，需要组织样本来测量脱碘酶活性。
We need a biopsy, we need a tissue sample to measure deiodinase activity.
这不是我们能在血液中检测的。
This is not something we do in the blood.
血液中不含脱碘酶。
Blood doesn't have deiodinases.
所以我们需要替代指标，如何估算此处的脱碘酶代谢情况？
So we need a surrogate, how can we estimate what's happening in terms of deiodinase metabolism here?
而反T3与T3或T3与反T3的比值就是替代指标。
And the reverse T3 to T3 or T3 to reverse T3 ratio is the surrogate.
是的，如果T3与反T3比值上升，说明你的激活功能增强而非失活。
Yeah, if T3 to reverse T3 is going up it means you're activating and not so much inactivating.
但当这个比值反转时，情况就相反了。
But the opposite happens when the ratio inverts.
因此我认为这是目前估算代谢情况的最佳比值指标之一。
So I think that that's one of the best ratios we have to estimate what's happening.
但再次提醒，这是个不错的估算，因为影响T3与反T3比值的因素有很多。
But again remember this is a good estimate because there are multiple factors affecting the T3 to reverse T3 ratio.
甲状腺仍在分泌一些，既有分泌过程也有清除过程。
The thyroid is still producing some, there's the production and there's the clearance.
所以这并不纯粹反映分泌情况，还包括清除作用。
So this is not purely reflecting production, there's also clearance.
但它确实有用。
But it is useful.
现在你提到这是D1。
Now you mentioned that this was D1.
给我们讲讲D2和D3吧。
Tell us about D2 and D3.
它们存在于哪里？
Where do they reside?
它们
What do
它们的作用是什么？
they do?
D2与D1的工作原理非常相似。
D2 works very similarly to D1.
然而，D2是一种卓越的酶。
However, D2 is a superb enzyme.
需要说明的是，D2对T4的亲和力是D1的1000倍。
Just so you know, D2 has 1,000 fold more affinity for T4 than D1.
D1是一种低效的酶。
D1 is a lousy enzyme.
尽管D1是最早在肝脏和肾脏中发现的，但D2的效率要高得多。
Even though D1 was the first one discovered in the liver and the kidneys, but D2 is so much more efficient.
它就像一种超级酶。
It's like a supercharged enzyme.
如果你问，甲状腺外产生的T3——大部分T3确实在甲状腺外产生——那么是谁在甲状腺外产生T3呢？
If you ask, okay the T3 that's produced outside of the thyroid, most T3 is produced outside of the thyroid, who produces T3 outside of the thyroid?
是D1还是D2？
Is it D1 or D2?
70年代的研究表明这是D2途径。
Studies done in the 70s show that is the D2 pathway.
甲状腺外生成的T3中，约80%由D2产生。
D2 makes about 80% of the T3 that's made outside of the thyroid gland.
尽管讨论甲状腺功能减退时D1可能发挥作用，但它仅生成20%的T3。
D1 makes only 20% although when we talk about hypothyroidism there could be a role for D1.
D1同时生成T3和反T3。
D1 is making both T3 and reverse T3.
确实会生成少量反T3。
Makes a little bit of reverse T3, yes.
但反T3的主要生成者是第三种脱碘酶——D3。
But the king of reverse T3 is the third deiodinase, is D3.
D1和D2主要起激活甲状腺激素的作用。
D1 and D2 they activate thyroid hormone mostly.
D3只做一件事，就是使甲状腺激素失活。
D3 only does one thing, inactivates thyroid hormone.
D3会消灭一切。
D3 kills everything.
D3将T3转化为T2，一个无活性的分子。
D3 takes T3 and transforms it into T2, a dead molecule.
那么T3去了哪里？
So where does T3 go?
T3遇到D3就会被彻底灭活。
T3 goes to D3 and it's killed completely.
D3是一种高效酶，对T3有高度亲和力。
D3 is a very effective enzyme, has high affinity for T3.
它还能将T4转化为反T3。
It also takes T4 and makes reverse T3.
因此D3既能使T3失活，又能确保T4不发挥作用——它会将T4转化为反T3。
So D3 inactivates T3 and makes sure T4 doesn't do anything, takes T4 and makes reverse T3.
所以D1会产生反向T3，但量非常少，因为D1对T4的亲和力并不强。
So D1 makes reverse T3 but very little because the affinity of D1 for T4 is not that great.
因此当你思考时，D3和D2是最强大的脱碘酶。
So when you think about it D3 and D2 are the most powerful deiodinases.
D2负责生成T3，D3则负责消除并灭活甲状腺激素。
D2 making T3, D3 eliminating, inactivating thyroid hormone.
主要是通过D2的作用吗？
Mostly through making D2?
没错。
That's correct.
必须是D2。
It has to be D2.
那么哪种酶会产生最多的反向T3？
So which enzyme makes the most reverse T3?
D3。
D3.
好的。
Okay.
所以D3基本上是个无效通路。
So D3 is basically a dead pathway.
那么是什么决定了它走D2路径（只是将激素移出口袋）还是生成反向T3（实际上会形成另一个分子受体阻止T3到达）？
And what determines if it goes down D2 which just takes the hormone out of pocket versus making reverse T3 which actually puts another molecule receptor that prevents T3 from getting there.
看起来生成反向T3实际上更具抗甲状腺作用。
It seems that making reverse T3 is actually more anti thyroid.
所以反向T3不会结合到
So reverse T3 doesn't bind to
口袋上？
the pocket?
它不会。
It does not.
不会。
No.
那么，反向T3和D2在无效性上有什么区别？
So what's the difference in futility of reverse T3 and D2?
你有一个T3分子。
So you have a molecule of T3.
好的。
Okay.
它具有所有这些生物活性。
Which has all of this biologic activity.
好的，是的。
Okay, yes.
将其转化为反向T3与转化为T2有什么区别？
What is the difference between turning that into reverse T3 versus turning it into T2?
没有区别。
No difference.
T2是无效的，反向T3也是无效的。
T2 is dead, reverse T3 is dead.
所以没有碎片。
So there's no pieces.
T2没有任何作用。
T2 doesn't do anything.
那么我们是否可以通过实验室检测T2，并获取有关甲状腺活性与非活性平衡的有用信息？
So we could measure T2 in a laboratory assay and also get useful information about the balance of thyroid, active versus inactive thyroid?
并不完全是这样。
Not really.
我的意思是我们可以检测T2，但T2的半衰期极短，因为随着代谢钻石结构向下延伸，你了解的信息会越来越少，比如有多个代谢途径都会汇聚到T2。
I mean we could measure T2 but T2 has an extremely short half life because as you go down this diamond of metabolism you learn less and less because there are multiple pathways converging to T2 for example.
你有多种途径可以生成T2。
You have different ways of getting to T2.
因此反向T3更有检测价值，因为它至少能存留几个小时。
So reverse T3 is more useful to measure because it at least sticks around for a few hours.
完全正确。
That's exactly right.
而反T3是T4的直接代谢产物。
And reverse T3 is the immediate metabolism of T4.
所以你可以确定，一旦反T3形成，就不会再产生其他物质了。
So you really know that once reverse T3 is made, there's nothing else that's going to come out of there.
身体会回收利用那些碘吗？是的，绝对会。
Does the body recycle that iodine Yes, absolutely.
是的。
Yes.
大部分碘都会被回收利用。
Most iodine is recycled back.
那么不存在从反T3回到T3的代谢途径吗？
So there's no pathway to go from reverse T3 back to T3?
没有。
No.
这是条单行道。
It's a one way path.
没错。
Exactly.
好的。
Okay.
在开始讨论两种极端状态（亢进和减退）之前，关于甲状腺激素的正常功能还有什么要补充的吗？
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?
我们可能需要回过头再谈谈下丘脑和促甲状腺激素的调节。
We should probably go back and say a little bit more about the hypothalamus and TSH regulation.
对。
Right.
下丘脑是这里一切的关键。
The hypothalamus is the key to everything here.
下丘脑会分泌一种称为促甲状腺激素释放激素（TRH）的激素。
So the hypothalamus produces this hormone that's called TRH or TSH releasing hormone.
这是一种小肽类物质，释放到血液后会迅速作用于下丘脑并立即进入脑垂体。
It's a small peptide that is released in the blood that baits the hypothalamus and immediately comes into the pituitary gland.
垂体是制造TSH的地方。
The pituitary gland is where TSH is made.
因此，如果下丘脑因意外、肿瘤或手术遭到破坏，TSH就无法生成，因为需要TRH来刺激。这就是问题所在，称为中枢性甲状腺功能减退。
So if the hypothalamus is somehow destroyed either by an accident or by a tumor or by surgery, then TSH is not going to be produced because you need TRH to stimulate And that's a problem, that's called central hypothyroidism.
我们可以稍后再讨论这个，因为许多患者声称自己患有中枢性甲状腺功能减退，对此稍作探讨很重要。
And we can talk about it later because many patients claim they have central hypothyroidism and it's important that we talk about it a little bit.
中枢性甲状腺功能减退是指垂体无法分泌足量的TSH。
So central hypothyroidism is when the pituitary gland is not producing sufficient amounts of TSH.
为什么TSH如此重要？
And why TSH is important?
仅仅因为它能刺激甲状腺发挥作用。
Only because it stimulates the thyroid to function.
我在不同患者群体中经常听到这样的讨论：'我的TSH是这样，TSH在起作用'。
And this is something I've seen a lot in different patient groups discussing oh my TSH is this, TSH is doing it.
不，TSH本身并不起任何作用。
No, TSH doesn't do anything.
甲状腺功能减退的所有症状都不能归因于TSH的变化，它必须通过甲状腺发挥作用。
None of the symptoms of hypothyroidism can be attributed to changes in It has to work through the thyroid gland.
因此TSH会刺激甲状腺生长、运作并分泌甲状腺激素。
So the TSH stimulates the thyroid to grow, to function, to secrete thyroid hormones.
让我
Let me
再重申一下以便大家理解。
just restate that so that people are following.
当TSH水平非常高时...正常范围大概是，假设实验室标准是0.5到4之间这类数值。
When TSH is very, very high So normal range would be, I'm just saying, let's say normal range in the laboratory is 0.5 to four, something like that.
明白了，是的。
Got it, yes.
所以如果你的TSH检测不到，我们接下来会讨论这意味着什么——说明你的甲状腺激素过量了。
So if your TSH is unmeasurable, we're going to talk about what this implies, it means you have too much thyroid hormone.
但你实际出现的症状是源于甲状腺激素过多，而非TSH过少。
But the actual symptoms you have are from too much thyroid, not from too little TSH.
没错。
That's correct.
反过来，如果患者就诊时TSH高达75（这种情况你我都有见过），他们感受到的症状通常相当严重，但这些症状并非由高TSH引起，而是由于甲状腺激素完全缺失
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, it's because the complete lack of thyroid
导致的。
hormone.
完全正确。
That's right.
只是想确保听众能理解这一点。
Just wanted to make sure that was clear for the listener.
不，绝对如此。
No, absolutely.
让我们回顾并重新梳理整个过程。
Let's go back and restate the whole thing.
人体有下丘脑、垂体和甲状腺。
You have a hypothalamus, you have a pituitary, you have a thyroid.
下丘脑分泌TRH，即促甲状腺激素释放激素。
The hypothalamus secretes TRH, thyroid releasing hormone.
对。
Right.
作用于垂体。
To the pituitary.
垂体分泌TSH（促甲状腺激素）作用于甲状腺，促使甲状腺分泌T4。
The pituitary secretes TSH, thyroid stimulating hormone, to the thyroid gland to secrete T4.
没错。
That's correct.
完全正确。
Absolutely.
甲状腺的独特之处在于它在血液循环中的水平。
And what's unique about the thyroid is that its levels in the circulation.
如果你观察T4和T3水平，会发现它们在一天内、一周内甚至一年内的变化都微乎其微。
If you look at T4 and T3 levels, they change very little during the day or during the week, even during the year.
存在一些微小的波动，大约10%到15%之间。
There's some minimal fluctuation, maybe 10%, 15%.
除了像疾病这样的极端情况外，哦对了，还有正常的甲状腺功能。
Outside of these extreme events like illness or Oh yeah, And normal thyroid function.
而且
And
这一点非常显著，因为如果你考虑胰岛素和胰腺，它们的变化很大。
that is remarkable because if you think about insulin and pancreas, that changes.
进食后胰岛素水平可能发生五、六甚至八倍的变化。
You can have a five, six, eight fold in change of insulin levels after you eat.
进食前与进食后相比，胰岛素水平会上升五到六倍。
Before you ate, after you ate insulin levels go up five, six fold.
皮质醇也是如此。
And same with cortisol.
告诉我你对这个的看法。
Tell me what you think of this.
你的观点要精妙得多。
You have a much more sophisticated view.
我通常告诉患者有四大激素系统。
I usually tell patients there are four big hormone systems.
分别是性激素系统、甲状腺系统、肾上腺系统，以及燃料分配系统。
You have the sex hormone system, you have the thyroid system, you have the adrenal system and then you have the fuel partitioning system.
也就是胰岛素-胰高血糖素系统。
So that's the insulin glucagon system.
你认为这种分类方式相对... 绝对正确。
Do you think that that's a relatively Absolutely.
全面吗？
Complete way to consider
这正是我过去给学生讲授内分泌生理学时采用的教学框架，我也是这样向他们展示这个系统的。
That's how I used to teach endocrine physiology for students, and that's exactly how I presented the system for them.
而在这四大系统中，你认为除了极端疾病情况外，甲状腺系统可能是最稳定的。
And of those four, you're saying outside of extreme scenarios of illness, the thyroid one is probably the most even Stable.
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而且
And
没错。
That's correct.
我是说，男性性激素系统
I mean, the male sex system
相对稳定。
relatively stable.
睡眠确实会影响FSH和LH，进而影响睾酮水平。
Sleep really can impact FSH and LH and therefore testosterone.
睾酮，是的。
Testosterone, yes.
确实会随着年龄增长而下降。
Does decline with age.
对，哦是的，甲状腺激素倒不会那么明显。
Right, oh yeah, not so much the thyroid.
这就是独特之处。
So that's what's unique.
这让许多医生和科学家感到困惑，既然这种激素如此重要，为什么它总是存在？
That puzzled a lot of physicians and scientists because if this hormone is so important, how come it's always there?
那么被调控的关键要素是什么？
So what are the key elements that are regulated?
我是说，如果你不改变激素水平，怎么能通过甲状腺激素来调节任何东西呢？
I mean if you're not changing the hormone level, how can you regulate anything with thyroid hormone?
这种思考方式非常有趣。
That's a very interesting way to think about it.
你也可以反过来论证。
You could argue the reverse.
你可以说正因为它极其重要，才必须像pH值一样维持在非常狭窄的稳态范围内。
You could argue it is so important that you have to stay in this very narrow homeostatic band like pH.
没错。
Right.
如果pH值如此重要，为什么它总是
If pH is so important, why is it always
七点整，完全正确。
That's seven point exactly right.
但其他激素并非如此运作。
But the other hormones don't work like that.
正是如此。
Exactly.
所以几十年来人们只会说，哦，甲状腺激素有允许效应。
So for a few decades people will just say, Oh, thyroid hormone has a permissive effect.
这让许多研究甲状腺的人非常不满。
Oh that upset a lot of thyroid studying people.
什么叫允许效应？
What do you mean permissive effect?
甲状腺激素太重要了。
The thyroid hormone is too important.
如果切除甲状腺，你会死亡。
If you remove the thyroid you die.
因此，当脱碘酶出现后，整个情况变得清晰多了。我们开始理解，尽管血液中的水平正常，但在受脱碘酶高度调控的组织中，qT3水平可能在几小时内发生十倍变化。
So the whole thing became much more clear when the deionases came about and we started to understand that even though in the blood levels are normal, in the tissue which is controlled a lot by the deionases, T3 levels can change tenfold in a few hours, for example.
我的博士论文研究的是棕色脂肪，这是一种褐色脂肪组织，其功能是帮助身体升温。
So my PhD thesis was on brown fat, which is this brown like adipose tissue that serves to warm up the bodies.
蝙蝠或任何从冬眠中苏醒的动物，它们的棕色脂肪会产生大量热量。
A bat or any animal that's waking up from a hibernation, the brown fat is going to produce a lot of heat.
而棕色脂肪含有大量Ⅱ型脱碘酶。
And brown fat has a lot of the type two deionase.
因此，如果将小鼠或大鼠暴露于寒冷环境中，或是唤醒冬眠中的动物，短短几小时内其组织中的T3水平就会激增十倍。
So if you expose a mouse or a rat to the cold or a waking animal from hibernation, rapidly in a few hours the T3 levels increase by tenfold.
不过在循环系统中并非如此。
Not in the circulation though.
循环系统中的激素水平是稳定的。
The circulation, the levels are stable.
如果你观察血液，会发现一切如常。
If you're looking at the blood, nothing is happening.
但在组织中，T3水平增长了十倍，这对该组织正在发生的能量激活至关重要。
But in the tissue T3 went up tenfold and that's important for the energy activation in that tissue that's happening.
所以当你看到棕色脂肪被激活时的实际热信号，主要是由T3转化驱动的。
So the actual thermal signature that you would see when brown fat is activated is largely driven by T3 conversion.
是的，
Yes,
是的，在内部——在
yes, inside- In
局部组织中。
the local tissue.
没错，正是如此，那可能是四十年前的事了。
That's right, yes exactly, that maybe forty years ago.
而且你未必能在全身系统中测量到那个T3。
And you would not be able to measure that T3 systemically necessarily.
不，
No,
绝对不是。
no absolutely not.
在'24年，我的论文研究中，我们将老鼠置于低温房间，24小时内棕色脂肪中的T3含量急剧上升，而血液中的含量却未改变。
In '24, so we, my thesis, we put rats in the cold room and in twenty four hours the amount of T3 skyrocketed in the brown fat and didn't change in the blood.
脂肪中的增长倍数是多少？
And what was the fold increase in the fat?
你观察到内部T3增加了多少？大约10倍。
Like how much T3 increase did you see inside About 10 fold.
10倍？
10 fold?
是的。
Yes.
我们使受体饱和了。
We saturated the receptors.
受体已经完全饱和了。
The receptors were fully saturated.
你无法再增加，因为它已经完全饱和了。
You couldn't have more because it was already fully saturated.
这真的很令人印象深刻。
It's really impressive.
当我们敲除棕色脂肪中的D2时，产生的热量就少得多，这表明棕色脂肪中局部T3激增确实非常重要。
And then when we knock out the D2 in the brown fat then the amount of heat produced was much less, showing that in fact that surge in T3 localized in the brown fat was really important.
现在人们可能会想，我才不在乎棕色脂肪呢。
Now people might think well I don't care about brown fat.
但同样的情况也发生在大脑中。
Well the same thing happens in the brain.
大脑中的大部分T3并非来自血液，而是通过II型脱碘酶在局部产生的。
Most T3 in the brain does not come from the blood, comes from being produced locally through the type two deiodinase.
所以我们从棕色脂肪研究中获得的认知，实际上也被我们应用于大脑研究。
So what we learned from the brown fat we actually took and used for brain studies.
我们大脑中的大部分T3都是由II型脱碘酶产生的。
Our brain, most T3 in our brain is produced by the type two deiodinase.
好的。
Okay.
现在对我来说由此立即产生的问题是，下丘脑是将T3作为产生TRH的信号来响应，还是它同时也在感知外周的任何变化？
Now the question that would immediately for me come from that is, is the hypothalamus responding to that T3 as its signal to make TRH or is it seeing anything in the periphery?
两者都有。
Both.
它是如何感知外周变化的？
How does it see the periphery?
嗯，通过
Well, through
供应下丘脑的血液。
the blood that baits the hypothalamus.
所以下丘脑位于外部，至少这些神经元所在的中央隆起区域是。
So the hypothalamus is outside, at least the median eminence is where these neurons are.
它位于血脑屏障之外。
It's outside of the blood brain barrier.
哦，我之前不知道这一点。
Oh I didn't know that.
是的。
Yes.
好的。
Okay.
室旁核（PVN）——产生TRH的地方，位于血脑屏障之外。
The PVN, the paraventricular nucleus where TRH is produced, is outside of the blood brain barrier.
因此T3和T4都能通过血液到达那里。
So T3 can get there from the blood, T4 can get there.
但让我们先
But let's make
确保大家理解这一点，因为如果我不知道，至少还有一位听众也不清楚。
sure people understand that because if I don't know that, at least one other person listening doesn't.
我作为一个非神经生物学家，原本以为下丘脑是完全被保护的，即位于血脑屏障内，因此外周激素无法与其沟通，只有能穿越血脑屏障的激素才能作用，但你的意思是？
I was assuming, not being a neurobiologist, that the hypothalamus was entirely protected from, I mean, it was within the blood brain barrier and therefore that these peripheral hormones weren't speaking to it and only hormones that could traverse the blood brain barrier, but you're saying?
内侧基底 hypothalamus，也就是内分泌调节的部分。
The medial basal hypothalamus, which is the endocrine regulation.
下丘脑的范围要稍大一些。
Hypothalamus is a little bigger.
我不确定下丘脑其他区域的情况，但内侧基底 hypothalamus 是在外侧的。
I'm not sure about the rest of the hypothalamus, but the medial basal hypothalamus is outside.
嗯，这样就完全说得通了，因为理论上它也是通过这种方式感知雌二醇、睾酮等激素的。
Well, really makes sense then because presumably that's how it's also sensing estradiol, testosterone, Exactly.
以及其他激素。
And other Exactly.
我居然没意识到这点，真是有点蠢，所以我们知道需要...
It's a little silly that I didn't So we know have to to
双方都
both both
有
have
我是说对所有事物，它都需要进行测量。
I mean to everything, I mean it needs to measure.
我们在哪里有很多D2受体？
Where do we have a lot of D2?
在下丘脑和垂体腺中。
In the hypothalamus and the pituitary gland.
因为记住，T4本身无法触发负反馈，它必须先转化为T3才能触发负反馈。
Because that's how, remember, T4 by itself cannot trigger the negative feedback because it has to be converted to T3 to trigger the negative feedback.
那谁来转化它呢？
And who converts it?
二型脱碘酶。
The type two deionase.
所以下丘脑有很多D2，垂体腺也有很多D2。
So the hypothalamus has a lot of D2, the pituitary gland has a lot of D2.
正因如此，它们能持续感知T3和T4水平
And because they have this, they can sense at all times T3 and T4.
它们会整合T3和T4两种信号，但T4需要先在局部转化为T3
They integrate both signals, T3 and T4, but T4 needs to be first locally converted to T3.
我们在棕色脂肪研究中获得的大量数据发现，实际上被用于理解大脑、下丘脑和垂体中的T3代谢机制
And so a lot of the data, a lot of the discoveries we made in the brown fat, we actually used for the understanding T3 economy in the brain and the hypothalamus and the pituitary gland.
这对甲状腺功能减退患者具有重大意义，我很乐意就此展开讨论
There are huge implications for patients with hypothyroidism and I'll be happy to talk
关于...是的
about Yes.
现在正在收听的听众可能好奇：为什么你们要深入探讨这么多生理学细节？
For the folks listening now who are wondering why are you guys going into so much physiology?
但若想真正理解如何治疗，这些生理学知识是必须掌握的
You have to if you want to understand how to treat this.
特别是在当前存在各种治疗学派的情况下（说得委婉些），我们必须理解这些生理机制，才能分辨哪些是真正有效的疗法，哪些是巫医迷信，哪些可能具有潜在危害
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 voodoo medicine, and what is potentially harmful.
你刚才说的非常重要，因为不幸的是，很多谈论甲状腺功能减退治疗的人对甲状腺生理学理解并不全面。
What you just said is so important because unfortunately a lot of people that talk about treatment of hypothyroidism has incomplete understanding of thyroid physiology.
我这么说并非要批评任何同行，但这是事实。
And I don't mean to criticize any of my colleagues in saying that, but it is a fact.
你听到的一些观点简直来自另一个世界。
Things that you hear that is just from a different world.
比如我们经常讨论的T3。
For example, we talk about T3 so much.
T3是具有生物活性的激素。
T3 is the biological reactive hormone.
T3才是关键所在。
T3 is the one.
但一个强势学派却主张永远不要测量T3。
But a strong school of thought says never measure T3.
他们声称不需要测量T3。
You don't measure T3.
为什么要测量T3？
Why would you measure T3?
这完全说不通。
It makes absolute no sense.
如果你仔细想想这半小时讨论的内容，我是说为什么不测T3呢？
If you think about all of what just discussed for this half hour, I mean why would you not measure T3?
它是具有生物活性的激素。
It's the biologically active hormone.
我把这归因于对甲状腺生理学理解的不完整。
And I attribute this to incomplete understanding of thyroid physiology.
就是这样。
That's it.
我是说这并不简单。
I mean it's not simple.
我必须说，我研究甲状腺已经大约四十年，四十五年了。
And I have to say I've been studying the thyroid for about forty years, forty five years.
我花了一些时间才理解。
It took me a while to understand.
我是说要把这些关键点联系起来，花了我数十年时间，因为我一直在听那些完全相同的观点。
I mean to put together important dots, it took me decades because I was listening to exactly those lines of thoughts.
我的T3啊。
Oh my T3.
但当你开始观察时，等等，我在实验室研究中关注的就是T3，这是我唯一关注的指标TPO。
But then you start looking, but wait a minute, in my studies in the lab I look at T3, it's the only thing I look.
可当我去诊所和病人交谈时，我却不关心T3了？
But then when I go clinic talking to my patients, I don't care about T3?
然后我的病人开始问我：医生，我们不该测T3吗？
And then my patients start asking me, Doctor, shouldn't we measure T3?
别担心这个。
Don't worry about it.
不，不用，我们只测游离T4和TSH就好。
No, no, we just measure free T4 and TSH.
但是为什么？
But why?
别担心这个。
Don't worry about it.
这非常重要，我亲身经历过，这就是为什么我如此专注于帮助甲状腺功能减退患者。
This is so important and I lived through this and that's why I became so focused on helping patients with hypothyroidism.
因为我曾认为自己对他们、对我的许多患者造成了伤害，因为我只是在重复那些没有充分考虑甲状腺生理学的人教给我的东西。
Because I myself thought I did a disservice to them, to many of my patients, because I was just repeating what I learned from the people that unfortunately did not take into consideration thyroid physiology.
所以当我们做
So when we do a
给病人做血液检测时，假设我们测量四项指标：TSH、游离T3、游离T4、反T3。
blood test on a patient, let's say we are measuring four things: TSH, Free T3, Free T4, Reverse T3.
通常还会提供另外两项检测，即T3和T4。
There are two other things that are typically offered, which is T3 and T4.
请向人们解释一下T3/T4检测与游离T3/游离T4检测的区别，因为之前我给你数据时甚至没提T3，直接说的是游离T3。
Explain to people the difference between the T3 T4 assay and the Free T3 free T4 assay because earlier when I gave you numbers I didn't even mention the T3, I went straight to the free T3.
TSH不受我即将解释的内容影响。
TSH is not affected by what I'm going to explain.
所以T3和T4会受到影响。
So T3 and T4 are affected.
循环系统中大部分T3和T4——我说的'大部分'是指99.5%——并非游离状态，它们与蛋白质结合。
So most T3 and T4 in the circulation, and when I say most I mean 99.5% are not in the free form, they're bound to proteins.
血液中有种蛋白质酷爱T3和T4，会将其捕获。
They're proteins in the blood that love T3 and T4, so they trap T3 and T4.
这些都是大分子蛋白质，比如白蛋白，还有其他蛋白质，但都属于大分子。
Now these are large proteins, albumin, there are other proteins, but these are large proteins.
是否存在类似性激素结合球蛋白的物质？
Is there an equivalent of sex hormone binding globulin?
是的，非常相似。
Yes, very similar.
它们由肝脏产生，最重要的是甲状腺素结合球蛋白。
They are produced in the liver, the most important is thyroxine binding globulin.
例如TBG就是甲状腺素结合球蛋白，它能同时结合T4和T3。
TBG for example is the thyroxine binding globulin which binds both T4 and T3.
我是说它们更喜欢结合T4而非T3，但实际情况下99%都是结合状态。
I mean they like more T4 than they like T3 but for practical purposes 99, this is all bound.
一旦与蛋白质结合，它们就不具有活性了吗？
And once bound to protein, they're not active?
它们必须
They have
先解离出来？
to become unbound?
正是如此。
Exactly.
它们无法进入组织，因为需要通过细胞膜，而结合状态下是无法通过的。
They can't go into the tissue because they had to go through the membrane and if they're bound, you can't go.
就像开车过门洞一样，根本行不通。
It's like going through a door driving a car, you can't.
所以你必须下车才能通过门。
So you have to step out of the car to go through a door.
甲状腺激素正是这样运作的。
That's exactly what thyroid hormone does.
因此只有极微量的甲状腺激素是游离的，存在于这些蛋白质之外。
So there's a tiny little fraction of thyroid hormone that's free, that's outside of this protein.
而这部分游离激素才能进入组织并产生生物活性。
And that is the fraction that gets into the tissues that is biologically active.
测量总T3与游离T3、总T4与游离T4的结果非常相似。
Now they are very similar measuring total T3 or free T3, total T4 or free T4.
然而这里存在一个问题。
However there is a problem.
这些蛋白质会发生变化。
These proteins can change.
比如雌激素就会影响甲状腺素结合球蛋白(TBG)的水平。
Estrogen for example affects the levels of thyroxine TBG.
因此有许多情况会影响T4的总结合量，但不会影响游离部分。
So there are a number of conditions that can affect the total amount of T4 that's bound but it doesn't affect the free fraction.
从诊断角度来看，我们更倾向于观察游离部分，因为这能反映实际进入组织的激素量。
So then from a diagnostic point of view we like to look at the free fraction because that's telling you how much actually is getting into the tissues.
总量多少其实并不重要。
It doesn't really matter how much.
最典型的例子是妊娠期——由于雌激素水平升高，甲状腺结合球蛋白增加，总T4上升，孕期T4值可能达到14、15，尽管正常上限约为12。
The extreme example is during pregnancy Because of the high levels of estrogen, TBG goes up, total T4 goes up, T4 during pregnancy can be a normal fourteen, fifteen, even though the upper limit of normal is about 12.
但只要游离部分正常就无需担心。
But the free fraction is normal so we don't have to worry about it.
这并不构成问题。
It's not a problem.
因此医生通常要求检测TSH、游离T4和游离T3。
Therefore doctors like to ask for TSH, free T4 and free T3.
关于游离T3和T3的检测，我们需要专门讨论T3的测量问题。
Now free T3 and T3 we need to talk about measuring T3.
这两项检测都不理想。
Neither one of the tests are good.
因为我们从未重视过T3，所以针对T3和游离T3开发的检测方法并非金标准。
Because we never cared about T3, the assays that we developed for T3 and Free T3 are not gold standards.
游离T4才是金标准检测方法。
Free T4 is a gold standard method.
游离T3和T3则不是。
Free T3 and T3 are not.
它们存在很大的变异性。
They have a lot of variability.
这些测量结果的批间变异系数很高。
The inter assay coefficient is high for these measurements.
因此这是种典型需要质谱检测的激素。
So this is a typical hormone that we need to use mass spec.
有研究表明，使用质谱检测才能获得血液循环中T3的真实数值。
And there are studies showing that when you use mass spec is that when you have a real number for T3 in the circulation.
现在，你可以用质谱法测量游离T3或总T3。
Now, you can measure free T3 or total T3 for mass spec.
两者都可以。
That's either one.
抱歉，托尼，让我确认一下。
Sorry, just to be clear, Tony, let me back up.
你是说当你去LabCorp Quest或其他信誉良好的实验室，医生勾选T4、游离T4时，默认会采用CLIA认证的质谱检测法吗？
You're saying when you go to LabCorp Quest or all of the reputable labs out there and the doctor checks off T4, free T4, it defaults into a CLIA approved mass spec assay?
不是。
No.
不是。
No.
T4是免疫测定法。
The T4 is an immunoassay.
T4是免疫测定法？
T4 is immunoassay?
不是。
No.
所有这些检测都是免疫测定。
All of these assays are immunoassays.
我说错了，我没有解释清楚。
I misspoke, I did not explain myself clearly.
T3是免疫测定。
The T3 is an immunoassay.
游离T3是免疫测定。
Free T3 is immunoassay.
这些都是免疫测定。
All of these are immunoassays.
然而，T3的免疫测定效果不佳。
However, the immunoassays for T3 are not good.
但T4的免疫测定是有效的。
But the immunoassay for T4 Yes.
我现在去LabCorp的话，是否有机会让我举个例子说明。
Is Now when I go to LabCorp, is there an opportunity so I'll give you an example.
我们从来不用免疫分析法检测雌激素睾酮。
We never check estrogen testosterone on an immunoassay.
德克斯科。
Dexco.
把那个检测方法扔进垃圾桶。
Throw that assay in the garbage.
没错。
Exactly.
而且我们总是特别要求用LCMS方法。
And we specify LCMS always.
这正是我们需要对T3做的检测吗？
That's exactly what we need to do for T3?
但你是说他们目前还没提供这项检测？
But you're saying that they aren't offering that yet?
我不这么认为。
I don't think so.
那么在研究环境之外，我们还没有CLIA认证的T3质谱检测方法吗？
So outside of a research setting, we don't have a CLIA approved mass spec for T3?
至少大实验室是知道的。
At least the big labs know.
也许某个精品实验室会提供这种检测。
Maybe there is a boutique lab somewhere that does that.
希望正在听我们讨论的人可能会知道，并告诉我们实际上存在CLIA认证的质谱检测方法
So hopefully someone listening to us will maybe know and will say actually there's a CLIA approved mass spec assay
这一点非常重要。
That for is so important.
这令人不安的原因如下。
So this is disturbing for the following reason.
当我们用免疫分析法检测质谱雌二醇和睾酮时，免疫分析法的数值误差太大，完全不具备临床参考价值。
When we run mass spec estradiol and testosterone by immunoassay, the immunoassay numbers are so bad that they serve no clinical use.
你不能根据这些数据做决定。
You can't make a decision based on them.
它们就是那么没用。
They're that useless.
所以我们干脆说，你知道吗，多花20美元绝对值得。
So we're just going to say, you know what, it's worth paying the extra $20 Absolutely.
T3的问题在于，游离T4免疫测定法效果不错，但我们不需要质谱分析。
The problem with T3, again free T4 immunoassays is good but we don't need mass spectra.
为什么
Why is
免疫测定法对T4有效但对T3无效呢？
that that the immunoassay works in T4 but not in T3?
这个嘛，我不清楚具体原因，问题出在哪里。
Well you have, I wouldn't know the specificity, what is the problem.
所有这些检测都取决于结合抗体的质量如何。
All these assays depend on how good the antibodies are that bind.
所以我们不
So we don't
知道从技术上讲是否无法开发T3的免疫测定法，还是现有的那个质量差，但可能有更好的方法。
know if it's technically not possible to develop an immunoassay for T3 or if the one that exists is just poor but another one could be better.
市面上可能有更好的抗体尚未被开发出来。
There's a better antibody out there that hasn't been developed yet.
是的，我们还没见过那种情况。
Yeah, we haven't seen that.
我观察到的是这些检测方法随着时间的推移有所改进。
What I have seen is that the assays have improved over time.
然而，它们仍远远落后于质谱法，尤其是在T3水平较低时。
However, they're far behind mass spec and especially when you have low levels of T3.
有一项发表的研究比较了T3的免疫测定法和质谱法。
There is a study published in which comparing immunoassay with mass spec for T3.
如果你的T3含量很高，两者还算可比，但如果数值在90ng/dL或100左右，质谱法就显得尤为重要了。
If you have a lot of T3 they are sort of comparable but if you are going around 90 ngdL, 100, that's where the mass spec becomes really important.
曲线在那里出现了分歧。
There is a divergence of the curves there.
所以我们确实需要在临床常规中使用质谱法检测T3。
So we really need to use as a routine clinically a mass spec for T3.
这非常重要。
It's really important.
我猜反向T3的情况也一样吧？还是说那个检测方法更...？
I assume the same is true for reverse T3 or is that assay more?
反向T3的情况比T3还要糟糕。
Reverse T3 is even worse than T3.
可以告诉你我们实际做过测试——虽然从未发表——我们用四种不同来源的反向T3检测方法测量同一样本。
I can tell you we actually did a test, we never published this, but we used four different sources of reverse T3 assays to measure the same sample.
结果简直离谱。
It was completely crazy.
所以这完全是无效数据。
So it's just noise.
没错。
Right.
人们会希望，比如当你去同一家信誉良好的实验室时，他们总是采用同一种检测方法，这样即便相对于质谱法来说可能不够准确。
One would hope that when you go to the same lab, for example, you go to a reputable lab, they will always use the same assay so that even though it might not be accurate in terms of Relative to the mass spec.
数值可能不精确，但至少能保持长期的一致性。
The exact value, but it's going to be precise, meaning that it's consistent over time.
明白。
Okay.
所以我们相信TSH数值，尤其是坚持在同一家实验室检测时。
So we trust the TSH number, especially when we're staying with the same lab.
我们相信T4和游离T4的结果。
We trust the T4 and free T4.
是的，游离T4。
The free T4, yes.
对于T3和反T3，当水平较低时需要格外注意，而这往往正是我们最关心的时刻，至少在甲状腺功能减退的情况下。
The T3 and reverse T3 we need to be mindful of when we have low levels, which of course is often when we care most, at least in hypothyroidism.
还有其他想讨论的话题吗？
Any other things we want to talk about?
我给你举个例子。
I'll give you an example.
我们知道遗传因素在男性雄激素方面起着重要作用。
We know that genetics play a significant role in androgens on the male side.
我们认为这可能与雄激素受体密度有关，有些人受体更多，因此需要并产生更多睾酮等等。
And we think maybe it has to do with androgen receptor density and that some people have more androgen receptors and therefore they need and make more testosterone than others, etc.
甲状腺激素存在多少遗传变异性和种系变异性？
How much genetic variability and sort of germline variability is there in thyroid hormone?
确实有一些。
There's a little bit.
我本来想说多年前没多少，但最近尤其是荷兰的研究者发表的研究表明，存在一些重要的遗传影响。
I would have said many years ago that there's not much but more recently folks, especially folks from The Netherlands have published studies showing that there is some genetic importance influence.
但这在临床上真的重要吗？
But is this clinically relevant, that question?
我不认为我们会根据遗传学改变任何治疗方案。
I don't think that we are changing anything based on genetics.
我不需要查看你的基因就能判断这个TSH值是否正常。
I don't need to look at your genes to say well this TSH is normal or not.
只需看TSH的范围，0.4到0.4或0.5之间。
Just look at the range in TSH, point four to point four or point five.
这个范围相当宽泛。
It's a broad range.
你什么时候需要关注这个？
When do you care about this?
当你治疗某个人的时候？
When you're treating someone?
我该把这个TSH值定在什么位置？
Where should I put this TSH?
4可以接受吗？还是我必须调到0.8？
Is it four okay or do I have to go to point eight?
这正是遗传学能派上用场的时候。
That's when genetics could help.
但影响的程度并没有那么大。
But the magnitude of the effect is not that great.
所以这会很有趣，我认为如今我们可以利用电子病历做到这一点，它们会保存你多年的检测结果。
So it would be interesting, and I think today we can do this with electronic medical record that they keep for years, your results.
如果能知道我患甲状腺功能减退前的TSH值会很有帮助。
It would be good to know how much my TSH was if I develop hypothyroidism.
我之前的TSH水平就是我想达到的目标值。
My previous TSH is where I want to be.
但我们真的会这么做吗？
But do we do this?
并不常见。
Not so much.
我认为这可能只适用于某些特定病例。
I think that this is maybe in some specific cases.
所以答案是存在遗传因素的影响。
So the answer is there is genetic influence.
不过，我不确定这在现阶段是否具有临床相关性。
However, I'm not sure that this is going to be clinically relevant at this point.
在我们进入病理学讨论之前，最后一个问题是关于男女差异的。
And then the final question before we get into pathology is male female differences.
差异有一点，但不大。
A little bit, not great differences.
女性的TSH范围比男性更宽泛。
The TSH range in women are broader than male.
男性往往对甲状腺的控制更为严格。
Male tend to keep a tighter control of the thyroid gland.
你会发现女性甲状腺功能检测结果存在更多变异性。
You see more variability in terms of the female thyroid function tests.
但再次强调，这具有临床意义吗？
But again, is this clinically relevant?
我不这么认为。
I don't believe so.
好的。
Okay.
那么现在让我们换个话题。
So now let's shift gears.
从高层次来看，甲状腺功能亢进和功能减退的比例如何划分？
High level, what is the split between hyperfunctioning thyroid and hypofunctioning thyroid?
作为一个非内分泌科医生，在我看来似乎甲状腺功能减退的病例比亢进更多。
It would seem to me as a non endocrinologist, I would see more hypo than hyper.
但具体比例是多少？
But what's the division?
如果你问甲状腺功能减退的患病率
If you ask the prevalence of hypothyroidism
在这些国家，根据所研究人群的年龄不同，我们认为大约有两千万甲状腺功能减退患者。
in these countries, depending on the age of the population you're looking, we think there are about twenty million patients with hypothyroidism.
大约占成年人口的4%到5%。
So it would be around four to five percent of the adult population.
而甲状腺功能亢进症的患者数量则以千计，远未达到百万级别。
Now hyperthyroidism, you're talking about thousands, you're not talking about millions.
可能只有几十万例，确实比甲状腺功能减退症罕见得多。
Maybe a few hundred thousands, maybe it's really a much rarer condition than it is hypothyroidism.
我每月大概只会遇到一两例甲亢患者。
I would see maybe one hyperthyroid or two hyperthyroidism per month.
同期我却会接诊四十名甲减患者。
At the same time that I will see forty patients with hypothyroidism.
甲亢并不算罕见，但确实较为少见。
It's not rare but it is certainly less common.
或许我们可以先从甲亢开始讨论，这样就能快速解决这部分内容，毕竟它显然不是我们讨论的重点。
Maybe let's start with hyperthyroidism to just get it off the table because obviously it's not what we're going to spend the bulk of our time on.
常见的病因有哪些？
What are the common causes for
甲状腺功能亢进症？
hyperthyroidism?
主要有两大病因。
You have two major causes.
一种是自身免疫性疾病，称为格雷夫斯病。
One is an autoimmune disease called Graves' disease.
当身体产生一种与甲状腺结合的抗体，且该抗体与促甲状腺激素（TSH）结合的位置相同时，就会引发此病。
It is when the body produces an antibody that binds to the thyroid gland and it binds to the same place where TSH binds.
甲状腺误以为有大量TSH，于是开始工作。
So the thyroid thinks that there's a lot of TSH so let me start working.
这是一种刺激甲状腺的抗体。
So it's an antibody that stimulates the thyroid.
甲状腺无法区分这种抗体和TSH。
The thyroid doesn't know the difference between this antibody and the TSH.
于是整个甲状腺均匀增生，产生大量甲状腺激素。
So the whole thyroid gland grows homogeneously producing a lot of thyroid hormone.
因此甲状腺功能亢进时，它会大量生成并分泌激素。
So you have a hyperfunctioning, it produces a lot and secretes a lot.
所以血液循环中T4和T3水平都会升高。
So you have high levels of T4 and high levels of T3 in the circulation.
突然间所有组织都暴露在过量的甲状腺激素中。
Now all of a sudden all the tissues are exposed to an excess of thyroid hormone.
这些组织原本适应于激素水平极其稳定的环境，现在甲状腺激素水平却突然高出两三倍。
They were used to a situation in those hormones that never changed, they're super stable, and now they have two or three fold higher levels of thyroid hormone.
所以患者会主诉心悸，这是最典型的症状。
So you will see patients complaining of heart palpitation, that's the number one symptom.
稍微运动就会感到心脏剧烈跳动。
For any exercise, anything the heart will just pound very heavily.
甲亢患者也会出现乏力症状。
Weakness is also seen in hyperthyroid patients.
患者会显得焦躁不安，可能出现失眠，对任何刺激都反应过度，反射亢进且迅速，同时伴有体重下降。
Jittery, patients are really agitated, they might have difficulty sleeping, they are very triggered by anything, they are very responsive, the reflexes are very rapid, very fast, and they lose weight.
因此，甲状腺功能亢进患者通常会明显消瘦。
So typically a patient that has hyperthyroidism will lose significant amount of weight.
有趣的是，你经常在和患者握手时就能做出诊断。
It's interesting, you frequently make the diagnosis as you shake hands with the patient.
你会注意到那只手温暖、非常柔软且潮湿，因为他们在出汗。
You're going to see that hand that's warm, very soft and wet because they are sweating.
他们正在产生大量热量。
Are producing a lot of heat.
记住甲状腺激素会刺激能量消耗，所以他们正在燃烧卡路里。
Remember thyroid hormone stimulates energy expenditure, so they are burning calories.
你只需握住他们的手就能看出他们存在未控制的甲亢症状。
You can just take their hand and you see that their uncontrolled hyperthyroidism is going on.
这就是其中一种甲状腺功能亢进类型。
So that's one type of hyperthyroidism.
为了确诊，你需要抽血检查，会发现他们的促甲状腺激素（TSH）基本为零。
And just to make the diagnosis, to confirm it, you're going to draw blood, you're going to see that their TSH is basically So press zero.
因为大脑在提示甲状腺激素过多，需要关闭分泌。
Because the brain is saying there's too much thyroid hormone, let's turn this off.
你要检测抗体吗？
You're going to draw for the antibody?
是的，你应该检测。
Yes, you should.
对。
Yes.
你会尝试测量抗体来确认，因为这可能是另一种甲状腺功能亢进，这就是区分的依据。
You will try to measure antibodies to confirm because it could be another type of hyperthyroidism, that's how you're going to distinguish.
但你会测量游离T4和T3，会发现两者都升高。
But you're going to measure free T4 and T3, and you're going to see both elevated.
无论是游离T4、游离T3还是总T3，都会看到各项指标升高。
Free T4, free T3 or total T3, you're going to see everything elevated.
抗体阳性检测，即TRAB或其它可测量的抗体检测方法，这将最终确诊为格雷夫斯病。
And the antibody positivity, it is called TRAB or there are different forms of antibody methods that you can measure, but that closes diagnosis of Graves' disease.
那么治疗方法是什么？
And the treatment for that?
治疗方法就是使用抑制甲状腺功能的药物，这是首选方案，属于药物治疗。
The treatment is you're going to give a drug that inhibits the thyroid gland, that's the number one, is the medical treatment.
药物主要有两种类型，我们通常选用能抑制碘进入激素合成酶的那一类药物。
There are drugs, there are basically two types of drugs, we try to use one type of drug that inhibits the enzyme that puts the iodine into the hormone.
这样甲状腺就无法生产甲状腺激素，因为它被抑制了关键合成步骤。
So there's no way that gland is going to produce thyroid hormone because it's inhibiting that step that's critical.
所以你要减少甲状腺激素的分泌。
So you're going to reduce the production of thyroid hormone.
还有其他治疗方式。
There are other forms of treatment as well.
还有手术治疗。
There is surgical treatment.
患者可以服药几个月，降低甲状腺激素水平后接受手术切除，要么切除整个甲状腺，要么切除四分之三的甲状腺，因为这样能减少分泌甲状腺激素的腺体质量。
Patients can 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 a thyroid because you are going reduce the amount of mass of gland that's producing thyroid hormone.
第三种治疗方式是放射治疗。
And the third form of treatment is radiation.
放射性碘。
Radioactive iodine.
放射性碘。
Radioactive iodine.
只需服用一剂放射性碘，因为它只集中在甲状腺上，就能杀死甲状腺。
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.
完全手术切除与放射性碘治疗的利弊各有哪些？
What are the pros and cons of complete surgical removal versus radioactive iodine?
这非常有趣。
That's very interesting.
在这个国家，大约二十年前，关于如何治疗甲状腺功能减退患者的讨论非常少。
In this country, maybe twenty years ago, there was very little discussion about how to treat patients with hypothyroidism.
当时普遍采用放射性碘治疗。
It was being given radioactive iodine.
所以患者来到诊所，确诊后离开时已经接受了放射性碘治疗。
So patients would come to the office, the diagnosis was made, they would exit already having received radioactive iodine.
首选的治疗方式就是放射性碘治疗。
The number one form of treatment was radioactive iodine.
在欧洲和其他国家，他们并没有这种偏好，他们会选择药物治疗，使用抑制甲状腺的抗甲状腺药物。
In Europe and other countries they didn't have such a preference, they would go for medical treatment with the drugs, the anti thyroid medication that inhibits the thyroid.
药物治疗的问题在于需要持续服用一至三年，寄希望于患者能够进入缓解期。
So the problem with the drugs is that you have to take them for one or two or three years hoping that the patient will go into remission.
随着甲状腺激素分泌减缓，身体承受的压力水平降低，抗体产生会自行减少，从而进入缓解期。
So as you slow down the production, you decrease the level of stress to your body and the production of antibodies will reduce by itself so that you will go into remission.
大约30-40%的患者能够进入缓解期。
About thirty-forty percent of the patients go into remission.
治疗时间越长，患者缓解的比例就越高。
The longer you treat the higher the percentage of patients.
所以你可以给患者两个选择：要么现在就烧掉你的甲状腺，要么服用这种药物两到三年，期待病情好转。
So you would offer the patient I can either burn your thyroid right now or you can take this drug for the next two or three years hoping that you're going to get okay.
你会好起来的，没错，正是这样。
You'll get better but yeah exactly.
确实如此。
Exactly.
第三种选择是手术。
Now the third option was surgery.
人们根本不喜欢手术。
People didn't like surgery at all.
如果有另外两种选择，谁愿意接受麻醉呢？
Mean who wants to go under anesthesia if I have these two other options?
手术始终是较不受欢迎的途径。
Surgery was always the less preferred route.
如今我们知道放射性碘并不那么安全。
Now today we know that radioactive iodine is not that safe.
会有什么后果？
What are the consequences?
有很多
There are lots
研究表明，接受放射性碘治疗的患者癌症发病率上升，可能罹患多种癌症。
of studies showing that you could have increased cancer, different types of cancer in those patients that take radioactive iodine.
主要是颈部局部癌症还是全身任何部位？
Local cancers to the neck primarily or anywhere in the body?
我记得是乳腺癌和肺癌，不确定，需要再确认一下。
I think it was breast cancer that was found in lung cancer, I'm not sure, I'll have to check on that.
但接受放射性碘治疗的患者确实癌症发病率更高。
But there is increased incidence of cancer in patients that take radioactive iodine.
所以现在人们逐渐放弃放射性碘治疗，重新选择抗甲状腺药物和手术治疗。
So people are now moving away from giving radioactive iodine and they are going back to treatment with medicine with the anti thyroid drugs and the surgery now.
为什么选择手术？
And why surgery?
因为如今外科医生的技术已非常精湛。
Because surgeons are extremely skillful today.
我们有专门从事甲状腺手术的外科医生。
We have surgeons that only do thyroid gland.
外科医生每年可进行一百到一百五十例甲状腺切除术。
Surgeons can do between one hundred and one hundred and fifty thyroidectomies per year.
这些是最优秀的医生。
Those are the best ones.
我的意思是，如果你去看外科医生，你不会想找那种每年只做10例手术的医生。
I mean if you go see a surgeon you don't want to go to that surgeon that operates 10 patients per year.
你至少需要找有100例手术经验的医生。
You want to have at least 100 cases.
因此手术已成为非常可行的选择，这需要与患者讨论，考虑年龄等多方面因素后选择最适合的方案。但总共有这三种治疗选项。
So surgery became a very viable option and this needs to be discussed with the patient, what is the best option for that patient, considering age, considering a lot of things, But those are the three options.
当你选择手术方案时，是否相对容易根据实验室数据判断需要切除多少甲状腺组织？
And when you do the surgical option, is it relatively easy based on the labs to figure out what volume of thyroid to remove?
还是你们基本上总是切除四分之三
Or do you always take basically three quarters
我认为他们总是采取相同的做法。
I of the that they always take the same thing.
我的意思是这要由外科医生来决定，但我从未见过相关讨论。
I mean I would defer that to surgeons but I've never seen a discussion.
我想理念是：我要采取能确保治愈这位患者的方案，但我无法保证那些患者
I think the idea is that let's take something that I know I'm going to cure this patient, but I cannot guarantee that those patients
是的，你无法保证他们可能不需要一点甲状腺替代治疗。
Yeah, you can't guarantee they might not need a little thyroid replacement.
最终他们都会需要的。
That's eventually they will.
因为刺激甲状腺的自身免疫疾病同时也具有破坏甲状腺的成分。
Because the autoimmune disease that stimulates the thyroid also has a component of destruction of the thyroid.
所以手术后十年又十年，会有大量患者发展为甲状腺功能减退。
So ten years after surgery and ten years after, you will have a great number of patients that evolve to hypothyroidism.
那么最后一点，正在收听我们节目的格雷夫斯病患者，20年前接受过放射性碘治疗的，他们是否需要做额外的癌症筛查？
So final point on this, people that are listening to us who have had Graves' disease, who 20 ago received radioactive iodine, should they be doing additional cancer screening?
我认为他们应该咨询医生。
I think they should talk to their doctor.
我认为他们应该咨询医生，询问现阶段该采取什么措施。
I think that they should talk to their doctor and ask what they should be doing at this point.
好的。
Okay.
那么另一种甲状腺功能亢进的表现形式，通常表现为
So the other form of hyperthyroidism, which usually shows up as
热结节。
hot nodules.
结节，对。
A nodule, yeah.
这只是一个增生，一个结节，甲状腺中的一个肿块，可能是单发的，也可能是多结节性甲状腺肿，会自主分泌大量甲状腺激素。
It's just a growth, a nodule, a lump in the thyroid that will, or maybe either a solitary one or a multinodular goiter that will produce bites autonomously, a large amount of thyroid hormone.
所以这就像是一个功能亢进的腺瘤。
So this is like a hyper functioning adenoma.
没错。
That's correct.
这种情况可以通过手术治疗。
And this can be treated surgically.
我们是用药物治疗还是历史上常用的放射性碘治疗？
Do we medically treat this or use radioactive iodine historically?
这三种方式都可以采用。
The three forms can be used.
不过，由于这是增生组织，它们往往会继续生长。
However, because it's a growth, these things tend to grow.
它永远不会自行缓解。
It will never go in remission.
虽然可以服用抗甲状腺药物，但由于这不是自身免疫性疾病，所以没有缓解的可能。
You can take the anti thyroid drug but there's no chance that this is going to go into remission because it's not an autoimmune disease.
因此服用抗甲状腺药物是为了降低甲状腺激素水平，而根据患者年龄和整体状况，很可能最终需要手术治疗。
So you would take the anti thyroid drug to reduce the levels of thyroid hormone and most likely that patient should go to surgery depending on the age, depending on the whole thing of the patient.
那么，他们能用放射性碘治疗吗？
Now, can they be treated with radioactive iodine?
是的，绝对可以。
Yes, absolutely they can.
因为这是个单一的热结节，所以需要给这位病人用更低剂量吗？
Do you need a lower dose for this patient because it's a single hot nodule?
不，通常你会使用相似的剂量。顺便说一句，剂量完全是经验性的，有不同公式计算剂量，但最终都在8到10毫居里之间，病人带着这些剂量回家。
No, usually you would use a similar dose And by the way the dose is completely empirical, there are different formulas to calculate dose, but in the end it's all between eight and ten millicuries and the people go home with those doses.
所以我的倾向是，如果你有个结节，我认为现今手术效果非常好，你应该认真考虑手术切除。
So my bias is if you have a nodule I think that surgery is so good today that you should strongly consider removing it surgically.
好的，现在我们来谈谈甲状腺功能减退症，这显然更为常见。
Okay, so now let's talk about hypothyroidism which is obviously far more common.
这就是所谓的内分泌科医生的日常工作了。
This is the so called bread and butter of the endocrinologist.
但也有许多病因，包括一些无法确定具体原因的病例。
But there's also many etiologies including some for which there's no identifiable cause.
那么让我们从常见情况开始，逐步深入探讨。
So walk through the Let's start with the horses and go to the zebras.
甲状腺功能减退的诊断有多少次是基于患者向初级保健医生陈述'我感觉不适，有以下症状'而做出的，又有多少次是通过年度筛查测试发现异常（通常是TSH显著升高）从而需要进一步检查的？
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, something shows up, usually a very elevated TSH, that then warrants further investigation.
这两种情况的比例如何分配？
What's the breakdown between those two scenarios?
答案随着时间推移而变化。
The answer evolved over time.
对吧？
Right?
在我几十年前刚开始行医, 接诊病人时，你实际上是通过症状来诊断或产生'这个病人可能患有甲状腺功能减退'的假设。
It used to be when I started doing medicine, seeing patients decades ago, you would actually diagnose or make the hypothesis, oh this patient might have hypothyroidism because of the symptoms.
现在，我记不清上一次仅凭症状诊断甲状腺功能减退是什么时候了，因为这太容易了。
Today, I cannot tell you the last time I made the diagnosis of hypothyroidism just because it's so easy.
每个病人都带着化验单来看病。
Everyone's showing up with labs.
TSH被用作常规检测项目。
TSH is used as a routine test.
这项检测非常有效，能筛查出所有问题。
It's so good, the test, that you pick up everything.
所以甚至在出现甲状腺功能减退的临床表现前，当TSH值达到七、八时，你就已经开始调查了。
So even before it has clinical manifestations of hypothyroidism you already have a TSH seven, eight and you start investigating.
因此现在很少见到通过症状来确诊甲状腺功能减退的患者了。
So it's rare to see patients that come with symptoms of hypothyroidism to make the diagnosis.
如今大多数情况下，我们都是通过TSH升高这一检查结果发现的。
In most cases today we have an elevated finding of elevated TSH.
当然，如果你去医疗资源匮乏的地区，那里的人没有固定家庭医生，也不做年度体检，这些患者可能会出现甲状腺功能减退症状并因此就诊。
Now it is possible that if you go to an underserved population that don't have primary care physician, they don't go for annual checkups, those patients might develop hypothyroidism and present clinically to their patients, to their doctors.
目前最常见、最典型的甲状腺功能减退病因是自身免疫性疾病。
Now the most cause, the bread and butter hypothyroidism is an autoimmune disease.
即患者体内产生的抗甲状腺抗体。
Antibodies that are produced by the patient's body against the thyroid.
患者的免疫系统无法识别甲状腺为自身组织，并试图摧毁它。
The patient does not recognize the thyroid as self and wants to destroy it.
因此免疫系统会攻击甲状腺，最终摧毁这个腺体。
So the immune system will target the thyroid gland, will destroy that gland.
这被称为桥本氏病或甲状腺自身免疫性疾病。
That's called Hashimoto's disease or autoimmune disease of the thyroid gland.
同时还会出现淋巴细胞浸润现象，你会发现大量淋巴细胞也在破坏甲状腺组织。
There's some level of cellular infiltration as well, you're going to find lots of lymphocytes destroying the thyroid as well.
结果导致甲状腺体积缩小。
And as a result the size of the thyroid reduces.
它变得萎缩。
It becomes atrophic.
体积可能缩小一半甚至更多。
It can reduce by half or even more than that.
由于甲状腺被破坏，激素分泌不足，血液循环中的甲状腺激素水平会下降。
And because it's destroyed the production is no longer there and the levels of thyroid hormone in the circulation will reduce.
这与甲状腺功能亢进症完全相反。
It's exactly the opposite of hyperthyroidism.
甲状腺激素水平会下降，组织将缺乏甲状腺激素。
It will come down and the tissues now will be missing thyroid hormone.
原本应该到达这里的激素在哪里？它们现在缺失了。
Where is the hormone that comes here and they don't have that?
甲状腺功能减退症的一个有趣现象是，当患者出现心力衰竭时，我们试图治疗心脏问题。
The interesting thing about hypothyroidism is that when a patient has heart failure we try to treat the heart.
我们使用药物让心脏泵出更多血液，降低外周阻力。
We give drugs to make the heart pump more blood, reduce peripheral resistance.
我们想要帮助心脏更好地工作。
We want to help that heart to work.
但我们不会对甲状腺这样做。
We don't do that for the thyroid.
我们只是对甲状腺置之不理。
We just forget about the thyroid.
我们不会说‘哦，让我们进行自身免疫治疗’，不不不。
We don't say oh let's give an autoimmune treatment, no no no.
人们很容易想到，让我们替换激素，让甲状腺自行消亡，因此甲状腺功能减退的治疗是通过所谓的替代疗法。
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.
所以我们想，只需给身体提供甲状腺原本产生的激素即可。
So we think let's just give the body the hormone that the thyroid was producing.
托尼，这其中隐含的未言明但必然正确的含义是，那个正在摧毁甲状腺的自身免疫状况，并未在身体其他部位造成任何有害影响。
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.
换句话说，要相信通过替代因免疫系统攻击甲状腺而流失的激素就能解决问题，你必须相信身体其他部位没有受到损害。
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.
对吧，但这实际上并不正确。
Right, but that's not actually correct.
确实不正确。
It's not.
我们是进化而来的。
We evolved.
确实如此。
Exactly.
我们正是这样想的。
We're thinking like that.
但后来你开始思考，等一下，我举个例子。
But then you start thinking, well wait a minute, I'll give you an example.
一位甲状腺完全健康的女性怀孕了。
A perfectly healthy woman with a healthy thyroid becomes pregnant.
作为筛查，我们将检测TPO抗体，这种抗体会破坏甲状腺。
And as a screening we are going to detect the TPO antibody, the one that destroys the thyroid.
检查结果显示，尽管她的甲状腺功能正常，但TPO抗体呈阳性，而且她目前怀孕了。
And a finding, okay she has positive antibodies, TPO positive, even though her thyroid is normal, but she's pregnant and she has positive TPO.
我们知道如果孕妇TPO抗体呈阳性，流产的风险会增加。
We know that if you have positive TPO and you're pregnant, your chances of having a miscarriage increase.
增加多少？
How much?
我认为不同研究系列会有不同的数据，但这并非无关紧要。
I think that different series will have different numbers, but it's not insignificant.
我需要稍后告诉你具体增加了多少风险。
I will have to get back to you on how much is increased.
而且早产的概率也会增加。
And there's also increased chance of prematurity.
仅仅因为TPO抗体呈阳性。
Just because the TPO antibody is positive.
即使TSH没有升高？
Even without rise in TSH?
在没有甲状腺功能减退的情况下。
Without hypothyroidism.
正是如此。
Exactly.
这本身就证明了要么TPO抗体自身在起作用，要么它的存在与某些我们尚未知晓的其他因素相关。
So that in itself is a demonstration that either the TPO is doing something on its own or its presence is associated with something else that we don't know.
所以自身免疫性疾病可能会与其他自身免疫性问题同时出现
So it happens that autoimmune diseases, they might come together with other autoimmune of
当然，在这种情况下，当你这样表述时，第二种情况似乎更有可能
course in that situation when you state it that way, it seems far more likely that it's the second of those two scenarios.
正是这个现在攻击甲状腺的免疫系统——我们可以通过TPO检测到——同时也在攻击
The very same immune system that is now attacking the thyroid, which we can detect through the TPO, is also doing attacking the
其他东西
something else.
因为胎儿是外来物
Because the fetus is foreign.
或者胎盘之类的
Or the placenta or whatever.
而且我们知道TPO阳性的患者中，可能有30%的人对脑组织或身体其他部位也有阳性抗体
And we know that patients that have TPO positive also, maybe thirty percent have positive antibodies against brain tissue, or different parts of the body.
那么你知道——显然我对产科一窍不通——现在是否所有孕早期女性都会做TPO筛查？如果结果阳性就会被转诊给高危产科医生？
So do you know, because obviously I know nothing about obstetrics, is this something where now any woman in her first trimester is getting a TPO screen, if it's coming back positive she's being shuttled to a high risk obstetrician?
他们应该这样做，虽然我不确定他们是否正在实施，但我绝对会推荐这个做法，因为我认为这很重要。
They should, I don't know that they're doing it but I certainly would recommend that because I think that's important.
另一个角度就是要回应你提出的关于这不是甲状腺特异性疾病的问题。
The other angle is just to address the question you made about not being a thyroid specific disease.
一旦患有一种自身免疫疾病，你可能还会患上其他疾病。
Once you have one autoimmune disease you might have others.
不孕不育可能与TP抗体阳性有关。
Infertility might be related with positive TPO antibody.
我这么说只是基于个人经验。
And I say this from an anecdotal point of view.
我曾接诊过一些患者，她们怀孕后会来找我做甲状腺复查，因为她们有甲状腺问题。
I used to see patients that once they become pregnant they come see me for a thyroid follow-up because they had a thyroid issue.
那么你的甲状腺问题是什么？
So what was your thyroid issue?
我之前怀孕困难，TP抗体检测呈阳性且数值偏高，虽然我没有甲状腺功能减退，但我的不孕不育医生认为TP抗体可能影响了受孕。
Well I had difficulty getting pregnant, my TPO antibody was positive, was high, I did not have hypothyroidism, but my infertility doctor thought the TPO antibody could be affecting.
于是我接受了一个泼尼松疗程。
So I went through a course of prednisone.
泼尼松龙。
Prednisolone.
泼尼松龙。
Prednisolone.
为了
To
降低TPO水平，之后我就怀孕了，现在我就站在这里。
reduce the levels of TPO and then I became pregnant and now I'm here.
第一次听到这个故事时，我很难相信。
The first time I heard that story I had a hard time believing.
我实际查看了数据，她之前确实有TPO阳性抗体，服用类固醇后抗体水平急剧下降，随后就怀孕了。
I actually looked at the data and in fact she had TPO positive antibodies before and after she took the steroids it decreased dramatically and she became pregnant.
所以我手头没有足够数据可以明确告诉你，比如百分之百的随机对照结果。
So I don't have the data to tell you, okay, a 100 randomized control.
不，我可以说我在那种情况下也见过很多患者。
No, I can tell I saw a lot of patients in that scenario as well.
我不知道这是否只是巧合，但我向许多不孕不育医生提出过这个问题，他们告诉我这是标准做法。
And I don't know if that's just coincidence, but I have asked that question to a lot of infertility doctors and they tell me it's a standard.
这非常有趣。
It's very interesting.
我认为像你这样同时扎根实验室的医生拥有一种真正的奢侈，那就是你能与那些基本上在为你提供假设的患者互动。
I think physicians such as yourself who live in the laboratory as well have a real luxury, which is you get to interact with patients who are basically giving you hypotheses.
完全正确。
That's exactly right.
我想起我跟随学习的导师，他的情况也是如此。
And I think about my mentor who I trained with and it was the same way for him.
他是一名肿瘤学家。
He's an oncologist.
但真正给予他最大实验室灵感来源的，正是他在照顾患者时的临床观察。
But it was really what he saw taking care of patients that gave him his greatest ideas for what to go and do in the lab.
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