The endocrine system: exploring thyroid, adrenal, and sex hormones | Peter Attia, M.D.

**Peter Attia** (0:11)
Hey everyone, welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you wanna take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are, or if you wanna learn more now, head over to peterattiamd.com forward slash subscribe.
Now, without further delay, here's today's episode.
Welcome to a special episode of The Drive.
In many of our previous podcasts, and as we'll see in upcoming episodes, we have spoken about and will speak about various hormones. And while in these conversations, we can get into some of the details, a lot of times we skip some of the basic biology and treatment implications around these hormones.
As such, I wanted to do an episode that answers a lot of these questions we get around the various hormones.
When thinking about the best way to do this, I reflect back on how I used to do this in pre-COVID days. I always used a whiteboard or a piece of paper, and I would draw sketches of the systems. As such, I've recorded a video series here where I go about these various endocrine systems, the thyroid system, the adrenal system, and the sex hormone system for both men and women. In these videos, I'll talk about how these hormones are regulated, what their feedback cycles are, and then talk a little bit about how we treat deficiencies of these hormones. So while we will be releasing this episode in audio format with all the videos combined into one audio, I really can't recommend highly enough that if you find this topic interesting, you really will need to watch the videos. Watching these videos instead will provide much more understanding around the topics that we're going to cover. And of course, as the cliche goes, a picture says a thousand words. So without further delay, I hope you enjoy this special episode of The Drive.
So let's start with the thyroid system. I've drawn a little bit of a schematic here. It's a bit oversimplified, and it's also at the same time a little bit messy. So I'm going to try to explain it, and hopefully it makes sense. You have the thyroid gland. This is the thing that sits in front of your larynx, you can actually feel the thyroid gland, and it's shaped as a shield, which is how it gets its name. And the thyroid gland is regulated directly via a hormone called TSH. So TSH is stimulated from the anterior portion of the pituitary gland, and it tells the thyroid gland to make T4 and T3. And the pituitary gland is regulated upstream by the hypothalamus, which stimulates it via a hormone called TRH. Now I'll come back to the regulation of these in a moment, but let's just go back to the thyroid gland. So the thyroid gland makes mostly T4 and a little bit of T3. Now where do the three and the four come from? What are they referring to? Well, they're referring to the number of iodines that are in the molecule. So not surprisingly, T4 has four iodines, T3 has three iodines.
What's the difference between them? The difference has to do with their biologic activity. When you think of all the things that the thyroid hormone does, for example, how it keeps you warm, aids in metabolism, controls things like the brittleness of your nails, your hair, bowel function, all sorts of things, all of the thyroid promoting functions are controlled by the active version, which is T3. T4, conversely, is the inactive version of the hormone. So if you're paying attention to what I just said, you'll note I just said that basically most of what comes out of the thyroid is T4, which is inactive. Now it's not entirely clear what the ratio is between these, but it's directionally about four or five to one. I think it's almost just as easy to imagine that virtually everything the thyroid is producing is T4.
So if the thyroid is producing T4, which is inactive, it needs to be converted into an active hormone in the body.
And that's where these enzymes called deiodinases come in. And as their name suggests, deiodinases remove one of the iodines from T4 to create T3, which is the active hormone. Now, the story gets a little bit more complicated because there are different types of deiodinases. But the three most relevant are D1, D2 and D3. So let's talk for a moment about these three deiodinases. D1 and D2 are quite similar in that they both convert T4 into T3. More about that in a moment. It's just where they do it that's slightly different. D1 is extracellular. It's on the cell membrane facing outward, whereas D2 is on the membrane of the endoplasmic reticulum, and it's facing internal to the cytosol. But put that aside for a moment and just keep in mind that D1 and D2 both convert T4 into the active hormone T3. This is the one that has all of the positive effects of thyroid hormone. Now D3 is different in that D3 takes T4 and makes something called reverse T3. Reverse T3 is very similar to T3, except for a very important difference, which is it doesn't activate the receptor that T3 activates. So it occupies the receptor without activating it. So in effect, you can think of reverse T3 as anti-T3. It basically blocks the effects of T3.