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The Connection Between Hypothyroidism and “Adrenal Fatigue”

How thyroid hormones impact your adrenal glands, cortisol levels, and energy production.

Is “adrenal fatigue” real? Here’s what we know about how stress impacts cortisol levels, and how a low T3 state can contribute to feelings of tiredness and fatigue.

Video Transcript

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What’s the connection between hypothyroidism and adrenal fatigue? 

There’s a controversy as to what “adrenal fatigue” is. There are some people, especially in the functional integrative space, who think chronic stress leads to the thyroid or the adrenal gland no longer being able to generate cortisol. It just becomes too fatigued. 

And I don’t know if that actually really happens, but it’s talked about a lot.


So here’s a classic definition of adrenal fatigue: 

Chronic stress leads to an inability of the adrenal gland to make cortisol, resulting in symptoms like tiredness, fatigue, sleep issues, etc. This stress drives up cortisol, which then blocks T4 and T3 from getting into cells, and that causes us to be tired and fatigued. 

And I don’t know how much of that occurs either, but people talk about it a lot. 

So one of the things that happens, definitely in acute situations, is the adrenal gland drives up some cortisol. It can also increase the production of something called catecholamines. And I’ve got a theory about this, and I don’t know that it’s all worked out yet, but just a theory. So something to talk about later…


So with acute stress, adrenal cortisol goes up. Why would the body increase cortisol? 

Well, if there’s some type of danger response, one of the things that cortisol is going to do is stimulate some of those defense mechanisms that can help increase an acute need for glucose, and it can have essentially an anti-inflammatory effect as well. 


So in time when stress is chronic and the adrenal gland can no longer make cortisol, people call that “adrenal fatigue.”

But is that what’s really happening? I don’t know. 

How do we typically identify that somebody has adrenal fatigue? 

Well, if you go to a functional medicine practitioner, a functional health coach, maybe an integrated practitioner, they may do salivary cortisol, they may do urinary cortisol and tell you, “Hey, yeah, your urinary metabolites are low, or your salivary cortisol is low, therefore you have adrenal fatigue.” And that’s how they get to this diagnosis. They see it low on the urine test and that you see it low on saliva. 

But then if you go into a GP, they’ll run a morning blood cortisol level, and your cortisol levels will probably be normal or high. And so how do we justify that? 

Somebody could have adrenal fatigue if the morning cortisol is normal. I see it all the time. The cortisol and the blood is normal, but the DUTCH test or salivary test or whatever metabolite test you’re doing to look at the free hormones, the cortisol and the urine, those things look a bit low.

So I think there’s a couple of things that we have to consider…

One: acute stress does increase cortisol. We know that it can increase your catecholamines as well, your fight or flight hormones, epinephrine, and norepinephrine, these fit into that category. 


But when we have chronic stress going on, we have the cell danger inflammatory process going on, and that can cause decreased production or decreased conversion of T4 to T3. 

That’s a lot of times, in my opinion, how hypothyroidism starts out. It doesn’t start at the gland, it starts at the tissue level because most people are experiencing signs and symptoms they associate with hypothyroidism long before they’re often diagnosed. 

So we get this decreased conversion of T4 to T3 that’s impacting some cells and tissues, maybe not all of them. And so the person’s maybe seeing some elevated lipids, maybe they have some signs and symptoms at the adrenal gland, and I’ll talk about that more in a second. 

But we have the cellular hypothyroid state go on, and when we have tissue hypothyroidism, we have less T3 inside the tissues, and we often can see that as a low total T3, a low free T3, a low free T3 to free T4 conversion.


And then we’re going to have reduced mitochondrial function. Now is that a problem? Because a lot of people just say, “Hey, just take mitochondrial support and that’ll fix your mitochondria.”

I often look at mitochondrial downregulation as an adaptation – at least early on – not the problem. Because when cells perceive danger, that kicks in their cell danger physiology, and the mitochondria is a huge sensor of that. 

So when that happens, there’s this whole change that goes on in the cell to slow down the metabolism and ramp up cell defense. And reduction of T4 to T3 conversion inside those cells and tissues is part of that process, a very important part. 

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So when we get this cell stress response, we get downregulation of T4 to T3 that helps support the downregulation of mitochondrial function. 

The problem is, if we have decreased mitochondrial function, that impacts something called the Krebs Cycle or the Citric Acid Cycle. We have downregulation of this electron transport chain, so we can make less ATP, the currency for energy in the cell. 

And when we have decreased ATP, this results in the increased circulation of something called adenosine. Adenosine is the base molecule, adenosine triphosphate. As I pull off those phosphate groups and I’m left with more adenosine, adenosine is your sleep molecule. When adenosine binds receptors, that’s what makes you tired and sleepy, and this is why you’re taking things like caffeine to block adenosine from binding to receptors so that your brain doesn’t feel as tired and sleepy. 

When you have more circulating adenosine because you don’t make a lot of ATP, you’re going to have some chronic fatigue because adenosine is constantly hitting your brain, telling you you’re tired and fatigued. 

Now your body will start to compensate for that – and that can be something like your catecholamine, your fight or flight hormones start kicking in to help. 

Or you might start adding things to try and artificially stimulate the brain and prevent it from feeling sleepy, but then that creates a potential problem as well. 


So as we have less T3 in the cell, we can also have less cholesterol transport into the adrenal gland. 

So the adrenal gland makes cortisol in one of two ways. 

One: in acute stages, the adrenal gland can make its own cholesterol and then convert that into cortisol. 

Two: the adrenal gland brings cholesterol from the bloodstream into the adrenal gland to make it into cortisol. And that’s the bulk of the cortisol we get is from that mechanism. 

Now, to get cholesterol out of the bloodstream and into the adrenal gland, you need T3. So if I have a low T3 state, guess what? I’m not going to be able to bring as much cholesterol into the adrenal gland to have it available to make into cortisol. 

The next step, once cholesterol is in the adrenal gland, it gets converted into something called pregnenolone in the mitochondria. 

But if I have a low T3 state, then I’m going to have reduced mitochondrial function. So I’m not going to be as efficient at converting cholesterol into pregnenolone and pregnenolone into cortisol. 

So these mechanisms can all contribute to decreased cortisol production. 


But why would my blood cortisol be normal if my doctor checks my blood waking cortisol? 

Well, you have something called a Cortisol Awakening Response. And remember, I said the adrenal gland can make its own cholesterol. It does this many times in acute situations, and it’s my thought process that this also is part of the cortisol awakening response. It’s this adaptive piece of our physiology that needs to occur. 

So even though somebody might have low urinary metabolites, lower saliva cortisol, the morning waking blood cortisol could be normal because they have this ability in situations. 

I think the Cortisol Awakening Response is one of those where the adrenal gland is just making its own cholesterol to support cortisol in the blood to help us with this whole awakening response. 

So if we have decreased cortisol and we have decreased thyroid hormone, the body’s probably going to compensate for energy production by increasing catecholamine – and this is where we can feel “wired but tired” because our body’s driving energy with fight or flight symptom hormones that cause the brain to be active, but the rest of the body is in crisis fatigue mode. 

I think there’s a concept, I haven’t proven this out yet, but I think there’s this thing I call “Tyrosine Steal.” My wonder is when we have this cell stress cell danger thing going on and we need to drive up catecholamines, are we stealing tyrosine from the thyroid gland to do that? I’ll make a video on that later…

Here’s some further listening for you on the connection between the thyroid and adrenal glands: Thyroid Answers Podcast Episode 135: Thyroid Adrenals, and Reproductive Health

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Hi, I’m Dr. Eric Balcavage, owner and founder of Rejuvagen. If you’re struggling with health issues or have questions, let’s chat. You can schedule a 15-minute call with me to get started.