Reverse T3: A Roadblock to Thyroid Success

Patient Expert
iStock

When it comes to hypothyroidism diagnosis and treatment, you will usually become familiar with more common tests like thyroid stimulating hormone (TSH), free thyroxine (Free T4) and free triiodothyronine (Free T3). But does your doctor test for reverse T3 (RT3?) Do you know what RT3 is, what it does, and how it can be a roadblock in feeling well with hypothyroidism?

It's useful to understand RT3 as part of your overall diagnosis and management of hypothyroidism, so let's delve into the details, so you can understand this test, and potentially incorporate it into your hypothyroidism treatment.

What is reverse T3?

To understand RT3, you need to understand the thyroid hormone production process. Your thyroid gland primarily produces thyroxine (T4), and a smaller amount of triiodothyronine (T3). T4 is considered a storage hormone. It needs to lose an atom of iodine to become triiodothyronine (T3), the active thyroid hormone that your body can use. This process of dropping an atom of iodine is known as deiodination, or more simply, T4-to-T3 conversion.

Conventional endocrinology assumes that most of the time, everyone converts T4 to T3 perfectly. They acknowledge, however, that physical illness or injury can derail the conversion process, and instead of converting the T4 into active T3, some of the T4 is converted into RT3. RT3 is inactive, meaning that it cannot perform the function of active T3 in your body or help to facilitate the delivery of energy and oxygen to your cells.  RT3 is not used by conventional endocrinologists and most physicians for diagnosis or management of thyroid disease in general, or hypothyroidism specifically.

Measuring RT3

RT3 is measured by a blood test. The two key U.S.-based labs have similar reference ranges for RT3:

  • LabCorp's range is 9.2−24.1 ng/ml
  • Quest's range is 8-25 ng/dL

Note that the RT3 test is not included in standard thyroid test panels and needs to be specifically added to a laboratory requisition. (Patients can also order an RT3 test in most states without a doctor's visit by using a direct-to-consumer laboratory services like MyMedLab or HealthCheckUSA.)

The controversy over RT3

As noted, the conventional endocrinology world does not test RT3 and does not use RT3 levels to make diagnosis and treatment decisions. They assert that the T4 to T3 conversion process almost always functions smoothly, and when elevated RT3 is detected, it has no bearing on thyroid function or treatment.

Integrative physicians and cutting-edge hormonal healthcare providers are, however, increasingly using RT3 as an important input in diagnosing hypothyroidism, and in making hypothyroidism treatment decisions.

They base their use of RT3 on several key concepts.

Many factors contribute to elevated RT3. RT3 can be elevated not only by illness or injury but by:

  • ongoing chronic physical stress
  • ongoing emotional stress
  • adrenal imbalances
  • low levels of ferritin (stored iron)
  • chronic infection or inflammation
  • ultra-low-calorie or starvation diets
  • long-term use of certain medications, such as beta blockers

According to the National Academy of Hypothyroidism (NAH):

"In a properly functioning thyroid, roughly 40 percent of T4 is changed to T3, and about 20 percent is translated into Reverse T3 daily. However, if one's thyroid is malfunctioning, or if the body needs to conserve energy and is under significant stress, the conversion ratio may change to 50 percent of T4 becoming Reverse T3. A significant change such as this greatly impacts thyroid function and hormone availability.”

RT3 is not just inactive; it blocks T3. According to integrative physician Kent Holtorf, M.D., Reverse T3 and T3 both fit into the same receptors. When you have more RT3 in your system, it competes with T3, attaches to receptors, and blocks T3 from reaching your cells. RT3 is “the body’s emergency brake.” In that sense, RT3 works as an antithyroid agent, going to your cells, and instead of stimulating energy and metabolism, it attaches to receptors, does nothing in the cells, but also actively blocks T3. RT3 is like a giant roadblock on your energy highway.

Elevated RT3 — even when other levels are in range — is evidence of hypothyroidism. According to Dr. Holtorf: “So, many people seemingly have normal thyroid levels, but if they have high Reverse T3, they're actually suffering from hypothyroidism.”

What is an elevated RT3 level?

Many integrative physicians consider RT3 to be elevated when the ratio of your Free T3/Reverse T3 is 20:1 or less. What that means is that you should have at least 20 times as much T3 as compared to RT3, assuming that both levels are using the same unit of measurement.

Example: To calculate the ratio, if your Free T3 is 420, and your RT3 is 24, divide 420 by 24, to get 17. Since 17 is less than 20, this is an unfavorable ratio and indicates excess T3.

Treating elevated reverse T3

Some physicians measure RT3 to help identify cellular hypothyroidism. Elevated RT3 or an unfavorable ratio — even when other levels are within the reference range — may suggest hypothyroidism that warrants treatment.

Some healthcare providers test for RT3 to help identify better hypothyroidism treatment options for patients taking levothyroxine. According to Dr. Holtorf, “These patients often experience debilitating fatigue, and continue to get worse in spite of taking T4 thyroid hormone medication.”

Integrative physician Amy Myers, M.D., is also a proponent of RT3 testing. Dr. Myers says: “If RT3 is high — you are likely converting too much T4 to RT3 and not enough to FT3, which can cause hypothyroid symptoms even if your TSH and T4 levels are optimal.”

Elevated RT3 and unfavorable ratios are primarily treated by adding — or replacing some of your thyroid treatment with — a T3 medication like liothyronine (Cytomel) or natural desiccated thyroid. Other approaches include:

  • Reducing your dosage of thyroid hormone replacement medication
  • Adding selenium supplementation
  • Dealing with underlying infections/inflammation
  • Dealing with underlying adrenal imbalances
  • Stress management

RT3 and mainstream endocrinology

Antonio Bianco, M.D., is one of the few endocrinologists who is looking at the role of T3 and RT3, and how they contribute to the poor resolution of hypothyroidism in patients on T4-only (levothyroxine) treatment. Dr. Bianco's research focuses on the role of type 2 deiodinase (D2) protein in the T4-to-T3 conversion process, and how genetic differences affect the expression of D2 in some people, causing lower T3 levels, higher RT3, and worsening hypothyroidism symptoms. According to Dr. Bianco: “The concept that localized ‘hypothyroidism’ coexists with normal circulating levels of thyroid hormone is well established.

He adds:

“At first glance, treatment for hypothyroidism seems straightforward; administration of daily tablets of levothyroxine … The main goal of levothyroxine monotherapy is to normalize the serum TSH level; the deiodinases are expected to normalize serum T3 on their own. Most hypothyroid patients respond very well to this approach … Clinical evidence indicates that not all parameters are normalized in patients receiving levothyroxine replacement therapy … In fact, for about 15 percent of patients on levothyroxine monotherapy, T3 levels remain below the normal range … is this why some patients on levothyroxine monotherapy remain symptomatic despite having normal TSH levels? Although this has not been clearly demonstrated in the existing clinical trials, it is almost intuitive to answer yes given that T3 is the biologically active form of thyroid hormone.”

As Dr. Bianco’s work gains traction and visibility, we can expect to see more studies and insights emerging on the role of RT3, and how it affects the diagnosis and treatment of hypothyroidism.

See more helpful articles:

How Your Thyroid Works

Thyroid Patients: Why You May Need T3

Making the Most of Your Hypothyroidism Treatment