Complete T4 and T3 Guide: What Do They Mean for your Thyroid?

If you’ve been diagnosed with a thyroid problem then you may, at some point, have thrown your hands up in the air in frustration.

After all, why does it even matter if you as a thyroid patient understand how your thyroid functions?

For one simple reason:

The thyroid patients who understand thyroid function are always the ones that feel their best.

It may sound daunting, but I promise that it’s not as confusing as you might think.

Let me explain what you need to know, in simple terms, starting with T3:

Understanding T3 (In Plain English)

T3 is probably the single most important thyroid hormone. 

Why?

Because it is the most biologically active thyroid hormone and most of the functions we associate with your thyroid gland come from the interactions of T3 in your cells (1).

T3 is short for the term Triiodothyronine which is the name given to this form of thyroid hormone. 

But how does your body create T3?

T3 is created FROM the most abundant thyroid hormone in your body T4. 

Enzymes, known as deiodinases, remove an iodine moiety at a certain place on the T4 hormone which turns it into the most active thyroid hormone T3 (2).

The process by which T4 is turned into T3 is known as thyroid conversion. 

And this conversion process is critical to understanding how your thyroid works. 

Thyroid conversion is the method that your body uses to tightly regulate thyroid function in the body. 

It is used to help create the EXACT amount of thyroid hormone needed at any given time and for all tissues. 

Think about it:

Your body has created a system in which it can convert, or not convert, T4 into the active T3 thyroid hormone based on the needs of the system (3).

So, if you are currently under a lot of stress, or if you need to produce more energy or heat, then your body can rev up the thyroid conversion process to produce more T3. 

On the opposite side of the spectrum, your body can also choose to slow down the conversion and put energy into more important bodily functions in instances where you may be critically ill. 

We see reduced conversion in people who are critically ill (4), those in the hospital, people taking certain medications, and so on (5).

More recently, we also see some patients with obesity and metabolic syndrome with lower-than-normal T3 levels due to a slowing of peripheral thyroid conversion (6).

In this way, thyroid conversion is becoming a more important topic because it influences how Doctors should treat and evaluate certain patients. 

This regulation is one of the most important concepts to understand in thyroid physiology. 

Thyroid conversion occurs ALL the time and occurs in major tissues such as your liver, and your gastrointestinal tract (7) but it also occurs in each cell. 

So what does T3 actually do?

T3 the thyroid hormone floats around in your bloodstream until it hits the target cell. 

Once there it can activate cellular function in two important ways:

The first is through non-genomic changes in the cell. 

Non-genomic changes include directly impacting enzymes and transporters on the surface of the cell itself (8).

An example would be the way that T3 activates calcium channels in the heart which may cause palpitations when ingested. 

The second is through genomic changes in the nucleus of the cell. 

These changes directly impact the expression of DNA and, therefore, which proteins are created. 

The proteins created from genetic changes go on to increase mitochondrial function, increase ATP production efficiency, and so on (9).

Put into plain English:

T3 helps increase your metabolism, improves your gastrointestinal tract, helps regulate your weight, regulates your mood, and so on. 

Perhaps the most important changes that occur secondary to thyroid hormone occur as the result of T3 changes in the cell. 

Understanding T4 (In Plain English)

The majority of thyroid hormone produced by your thyroid gland is actually in the T4 form (also known as Thyroxine). 

Your thyroid gland, if working properly, produces around 80% T4 and about 20% T3 (10).

This means that T4 is MUCH more abundant in your body when compared to T3. 

It’s also important to understand that T4 is NOT as biologically active as T3. 

This means that it doesn’t have the same cellular effects as T3 and it doesn’t activate your cells in the same way. 

So what is the purpose of T4?

T4 helps to serve as a reservoir for T3 conversion, so T4 levels are still critical to proper thyroid function. 

T4 also does have some cellular activity, but these are not felt to be as strong when compared to T3. 

T4 is important to understand because most of the medications that Doctors prescribe to treat hypothyroidism come in this form. 

The idea is that supplying the body with T4 (the less biologically active thyroid hormone) is safer when compared to using T3. 

T4 also has a longer half-life when compared to T3 (11) and comes with fewer side effects. 

What About T2 Thyroid Hormone?

T3 and T4 tend to get most of the attention when it comes to thyroid hormones, but there’s another one that you need to be aware of:

T2.

T2, also known as 3,5-Diiodo-L-thyronine (or T2 for short) is not as powerful or potent as T3 and T4, but it still does provide important physiologic effects.

The most important may be its propensity to impact basal metabolic rate or metabolism.

Some studies have shown that even though T2 is far less biologically active when compared to T3 (12) (it’s about 1/80th as potent), its impact on metabolism may be equal to or greater than that of T3.

Some studies attempt to compare T2 to T3 on the basis of its biological activity, but I don’t think that’s how it works.

T2 appears to act as a ligand on the thyroid hormone receptor which enhances the activity of T3 on your cells.

Through this mechanism, it not only provides its own benefits but appears to enhance the function of other thyroid hormones.

One of the most interesting aspects of T2 is not its mechanism of action, but the fact that it is available for purchase as an over-the-counter supplement.

Unlike T4 and T3, you don’t need a prescription from your doctor to take T2.

This provides you as a thyroid patient a unique and powerful way to adjust thyroid hormones in your body without the need of a doctor.

And because studies show that T2 can help increase energy metabolism (14), it’s a tool you may benefit from using.

T2 is a great option for thyroid patients who are taking standard thyroid medications but are not feeling their best.

T2 as 3,5 diiodo-l-thyronine is available in both capsule form and cream form.

You can learn more about the cream form here.

And you can learn more about the capsule form here.

What is Reverse T3?

On top of the active thyroid hormones, you also need to know a little something about the dreaded anti-thyroid metabolites.

Reverse T3, known as RT3 or 3,3′,5 triiodothyronine, is one of these.

It’s created from the conversion of other active thyroid hormones like T4.

But wait, didn’t we already mention that T3 is created from T4? How can reverse T3 be created from T4 as well?

Both statements are actually true. 

You can think about thyroid conversion as a fork in the road. 

Your body has the ability to turn T4 into reverse T3 or T3 and it must choose one or the other. 

If it chooses reverse T3 over T3 then there’s one less molecule of thyroid hormone that can be activated. 

Beyond “stealing” from your potential T3 supply, reverse T3 can also block thyroid action at the cellular level (15). 

So not only does the conversation of T4 into reverse T3 lower circulating T3, it also makes it more difficult for what little T3 remains to do its job.

In this way, you can think of reverse T3 as the major anti-thyroid metabolite and the enemy to any thyroid patient looking to feel their best.

Why does this conversion to reverse T3 occur?

In response to certain and specific conditions, some of which are under your control.

Some states which encourage the product of reverse T3 include:

• Inflammatory states (16)
• Obesity
• Metabolic abnormalities
• Exposure to LPS
• Exposure to EDCs
• Illness
• Medications

Reverse T3, like the other thyroid hormones we’ve mentioned (but with the exception of T2), can be measured in the serum through simple lab tests.

There’s some debate about whether or not ordering reverse T3 is beneficial, but my opinion is that it’s worth keeping an eye on from time to time.

TSH VS Thyroid Hormones

It may be confusing to hear about thyroid hormones such as T4 and T3 when you are so used to hearing about TSH. 

TSH, while important, is not necessarily more important than your thyroid hormones. 

TSH, known as thyroid stimulating hormone, is a hormone secreted by your pituitary gland. 

TSH then acts to stimulate the RELEASE of thyroid hormones from the gland. 

TSH doesn’t necessarily say how much T4 and how much T3 to produce, however. 

It just “stimulates” the gland to produce thyroid hormone in general. 

The actual activation and conversion of T4 into T3 (which is more important as it relates to thyroid activity) is controlled by the liver, gut, and individual cells. 

TSH is important, however, in helping to diagnose gross abnormalities in your thyroid gland and in helping to determine how “responsive” the gland is to TSH. 

If you have high TSH in your bloodstream then that is often a sign that you have LOW thyroid levels in the body or a condition known as hypothyroidism. 

High TSH is an indication that your thyroid gland is not responding to the TSH. 

Low TSH, on the other hand, may be an indication that you have TOO much thyroid hormone in the body (known as hyperthyroidism). 

TSH is an important factor in thyroid management, but it should not overshadow the evaluation of free thyroid hormones such as T3 and T4. 

In addition, there are situations in which the TSH becomes less helpful as a tool for evaluating thyroid function. 

You can read more about this concept here. 

Testing for T3 & T4 & Getting Optimal

Because of the importance of thyroid hormones in thyroid physiology, it’s important to evaluate and monitor their levels in your body. 

You can do this through simple blood tests for both hormones. 

These hormones should be evaluated in addition to the standard TSH (Thyroid stimulating hormone) which is often ordered to evaluate thyroid function.

TSH gives you an idea of how the pituitary is functioning and how responsive your thyroid gland is, but T3 and T4 give you much more actionable information on how thyroid hormone is being utilized in your peripheral tissues. 

Always use these blood tests in conjunction with TSH. 

You can find the list of thyroid hormone testing below:

• Free T3 – Free T3 is the number of FREE and ACTIVE thyroid hormone. Remember that T3 is the most potent and biologically active thyroid hormone. For optimal results, this value should be in the top 50% of the reference range (top 20% for weight loss). 
• Free T4 – Free T4 is the number of FREE and ACTIVE thyroid hormone but is NOT as biologically active as Free T3. For optimal results, this value should be in the top 50% of the reference range. 
• Reverse T3 – Reverse T3 is the anti-thyroid metabolite that competes for binding with T3. For optimal results you want this value to be less than 15 ng/dL. 

When using thyroid medication (such as Levothyroxine or Synthroid) you want to optimize your Free T4 level to be in the top 20% of the reference range and your free T3 to be in at least the top 50% of the reference range. 

If weight loss is your goal then aim for even higher free T3 levels (top 20% of the reference range). 

In order to achieve these levels, you may need to use a combination of T4 + T3 thyroid medications. 

This may require adding Cytomel or liothyronine to your existing dose of T4 or by switching to NDT medications such as Armour Thyroid. 

Final Thoughts

Understanding how T3 and T4 work in your body will help you to understand how well your body is functioning. 

Remember that your thyroid gland controls very important functions in your body ranging from your metabolism to your mood and everything in between. 

These functions are TIGHTLY controlled and regulated by your thyroid gland, thyroid hormones, and thyroid conversion.

Small changes, or dysfunction, to any of these systems, may result in quality of life issues that will manifest as weight gain, depression, fatigue, hair loss, and so on. 

If you suffer from hypothyroidism or another known thyroid disease, please make sure that you evaluate your thyroid hormones in addition to TSH. 

Ordering T3 and T4 will help shed insight into how well your body is utilizing thyroid hormones and how well you are converting thyroid hormones. 

If you find that you are not optimal, even if your TSH is normal, then you may need to have your medication adjusted to include different medications or a different combination of T4 and T3. 

Now I want to hear from you:

Have you had your T3 and T4 tested?

Are you suffering from high reverse T3 or other thyroid issues?

Are you taking thyroid medication?

Leave your comments below!