What is the function of T3?
The thyroid gland releases about ten times as much of the thyroid hormone T4 (thyroxine) as T3 (triiodothyronine). Normally, the liver and kidneys then convert much of the T4 to T3; about three quarters of the T3 circulating in the blood arises from conversion from T4 in these tissues.
T3 and T4 appear to have the same effects on the body, increasing the basal metabolic rate and causing many other physiological effects. The two hormones appear to stimulate the same thyroid hormone receptors found in tissues all over the body, so their function does not really differ, at least as currently understood (source: “Medical Physiology” by Boron, 2005).
In terms of its effects on the body, however, T3 is much more active and potent than T4. This is due to two factors. First, more T4 than T3 stays bound to carrier proteins in the blood (and therefore can’t signal hormone receptors). Second, T3 is more effective than T4 at binding and activating the thyroid hormone receptors. This is why the conversion of T4 to T3 is of such importance.
What is Reverse T3 and how is it related to T3?
Reverse T3 (also known as rT3) is a molecule that is very similar to T3 in structure. It is in fact an isomer of T3 (which means it has the same number and kind of molecules as T3, but in a different spatial arrangement). Unlike T3 and T4, rT3 has no known biological activity or effects. But it is normal to have some rT3 present. Your thyroid releases very little rT3. It is produced mostly in nonthyroidal tissue (such as the liver and kidneys). Like T3, it is synthesized from T4. T4 that is converted to rT3 is not available to be converted to the active version of the hormone, T3.
Under different circumstances, more of the T4 in the peripheral tissues may be converted to rT3 and less converted to T3, resulting in elevated levels of rT3 and reduced levels of T3. This can occur in many different types of chronic and acute illness, including in some autoimmune diseases. Exactly why and when this happens is not well understood, but it may relate to levels of stress hormones such as cortisol or levels of inflammatory substances.
The condition has been most studied under conditions of acute stress in severely ill patients. These patients show elevated rT3 and low T3; TSH and T4 are also affected if the condition becomes more severe. At this point, it is not clear whether these changes are an adaptive response to illness that might have some unknown benefit, or if these changes should themselves be treated. Theoretically, an elevated rT3 level paired with a low T3 level might indicate that the conversion of T4 to T3 is at least partially at fault for low T3 levels and a patient’s symptoms.
Why does taking T3 (as a second pill or through desiccated thyroid hormone) make me feel so much different from T4-only medication?
The answer to this is not yet clear, but some patients do report symptom improvement on T3, even after their TSH levels and T4 were in what is considered the normal range. In recent years, researchers and clinicians have explored whether treatment with T3 in addition to standard treatment with T4 might lead to better results for certain patients with hypothyroidism. The results of these studies have been mixed, and this topic remains quite controversial among endocrinologists, some of whom believe treatment with extra T3 might prove dangerous.
However, in a recent study of patients with hypothyroidism, 49% of patients preferred treatment with T3 and T4, compared to 15% who preferred T4 alone, and 35% who had no preference. Certainly, if certain patients are ineffectively converting T4 to T3 in the peripheral tissues (due to genetic variations in the responsible enzymes, or other environmental factors such as inflammation and stress) it might make sense that supplementing T4 with T3 might provide a better therapeutic response, at least in some patients.
Questions for your doctor
- Should I get might T3 levels tested? What about rT3 levels?
- Are there any risks to adding T3 to my regimen? How can I monitor them?
- Would a trial of a T3 product be appropriate in my case?
About the Author
Ruth J. Hickman, MD, is a freelance health, science, and medical writer. She specializes in writing about medical topics for the lay public and for health science students. She can be reached at [email protected] or through her website: ruthjhickmanmd.com.