Reverse T3 and Thyroid Dysfunction

If you’ve been on a ‘thyroid journey’ for a while now, you might be familiar with some of the big names in thyroid health. There’s TSH, T4, T3 and then there’s the thyroid antibodies. But have you heard about reverse T3? Put simply, reverse T3 is an inactive ‘thyroid hormone’, but one that can sometimes wreak havoc when everything else is seemingly functioning as it should be. In this article today, we’ll explore the role of reverse T3 in thyroid health and will discuss when and why you might consider having your rT3 tested. But first, let’s set the stage with a little recap of how the thyroid works.

A Recap on the Thyroid

To recap some of my other articles on the topic, the thyroid is a butterfly-shaped gland that sits in the neck and produces hormones that control our metabolic rate. To make the thyroid do its job, the brain sends out a chemical messenger called TSH, or ‘Thyroid Stimulating Hormone’. This hormone stimulates the thyroid to produce thyroid hormone, which is known as T4 (along with small amounts of another thyroid hormone, called T3).

T4 is released into the bloodstream and taken to various tissues, where it is converted into T3 - the active form of thyroid hormone. When T3 binds to our cells, it regulates things like our metabolism, body temperature and heart rate, to maintain homeostasis in the body.

A percentage of T4 is also converted into something called reverse T3 (rT3) - the inactive form of T3. Reverse T3 can bind to T3 receptors on cells, but it doesn’t evoke a response, which is why it is considered inactive. In effect, it competes with T3 at a cellular level. Because of this, researchers believe reverse T3 is a natural ‘buffer’ against hyperthyroidism; a protective mechanism to prevent thyroid overactivity.

Why Can Reverse T3 Be A Problem?

As I discussed above, reverse T3 is a natural by-product of thyroid hormone production and an important regulatory mechanism in the body. That said, in some situations, reverse T3 production can increase relative to T3 levels, and this can cause problems. Reverse T3 and T3 are natural antagonists of each other, meaning they compete at a cellular level for receptor sites on cells. If these receptor sites are blocked up with lots of reverse T3, then T3 itself can’t bind to the cells to exert its effects. This can result in symptoms of hypothyroidism, even if T3 levels are within range. This is why some patients may be experiencing symptoms of hypothyroidism, despite having adequate T3 levels in the blood - if their reverse T3 levels are very high, T3 can’t bind to the cells and do its job, meaning symptoms of hypothyroidism can occur. In such cases, it’s important to assess both reverse T3 and T3 itself, so the two can considered in relation to each other. If reverse T3 is elevated with respect to free T3, then it is important to work out why!

What Causes Elevated Reverse T3?

It’s important to remember that reverse T3 is always produced as a natural consequence of thyroid hormone production. This means that even patients with a well-functioning thyroid will still be producing reverse T3, and this is a normal, healthy occurrence. It also means the more thyroid hormone being produced, the more reverse T3 will be produced as well. Therefore patients with naturally high T4 production will produce more reverse T3 as well, but this is generally not a problem if T3 levels are within a good range as well.

What isn’t normal is when excessive amounts of thyroid hormone is shunted towards reverse T3 production, leaving little leftover to be converted into the active thyroid hormone. This can happen for a number of reasons including:

  • Stress (our stress hormone cortisol increases conversion of T4 into reverse T3)

  • Poor blood sugar management and insulin resistance

  • Inflammation

  • Starvation or crash dieting

  • Chronic illness

  • Certain nutritional deficiencies

  • Certain medications (such as glucocorticoids, Amiodarone and certain beta-blockers)

All of these factors contribute to increased conversion of T4 to reverse T3, potentially resulting in symptoms of hypothyroidism or thyroid dysfunction.

When looking at these factors, in many ways you can see how reverse T3 is a clever evolutionary adaptation by the body. During times of stress, famine or starvation, reverse T3 production increases, to slow the metabolic rate and conserve energy. Back in the cavemen era, this would have been a clever, protective adaptation when food supplies were low. In today’s world though, this ‘stress’ may take the form of a crash diet or a stressful work environment, but the effect on our thyroid hormones is the same: increased conversion of T4 to reverse T3, and a lower metabolic rate as a result. A similar effect is seen with glucocorticoid medications, such as prednisone, as these medications mimic the effect of our body’s own stress hormone, cortisol, causing increased shunting of T4 towards rT3 production.

When Should You Test Reverse T3?

For most patients with suspected thyroid dysfunction, a thyroid function test assessing TSH, T4 and T3 will be sufficient to identify hypo- or hyperthyroidism. Testing thyroid antibodies (such as TPO, Tg and thyroid receptor antibodies) is useful in identifying whether there is an underlying autoimmune disease contributing to or causing this dysfunction. In most cases, reverse T3 is not tested, as T4 and T3 are considered more useful in identifying and monitoring overt thyroid dysfunction.

When I might advocate reverse T3 assessment is when a patient is still experiencing symptoms of hypothyroidism, despite having a seemingly well-functioning thyroid. For example, if a patient is experiencing weight gain, low energy levels and hair-loss despite normal thyroid function, I may recommend testing reverse T3, in addition to looking at other potential causes of their symptoms (such as low iron levels, poor blood sugar management and so on). I may also recommend reverse T3 testing if the patient has such symptoms and has been under prolonged stress, or if they fulfil some of those criteria above for increased reverse T3 production - in these cases, identifying a raised reverse T3 can be helpful to shed light on why they may still be feeling hypothyroid, despite adequate thyroid hormone levels. Ultimately, if reverse T3 levels are raised, identifying the reason or reasons why is integral to addressing the problem - Whether its stress, insulin resistance, inflammation or nutritional issues, correcting these underlying factors will help regulate thyroid hormone metabolism and ideally, improve conversion of T4 to its more active form, T3.

Ultimately, if you’re experiencing unexplained symptoms of hypothyroidism, or symptoms that don’t fit the picture as told on your blood tests, it’s worth investigating these further and a conversation with your GP or naturopath may be all it takes to get the ball rolling!

Yours in health,

Niki x