Thyroid Blood Tests - What is Reverse T3?
I wrote this originally in 2012. However, I thought I would edit it and push it higher up my list of blog posts because it sits nicely with the other recent posts of Dr. Tania S. Smith that I have referenced. It seeks to make clear that there is still some value in knowing what rT3 is because it is a marker of poor conversion and potentially blunted T3 action.
T4 is a relatively inactive hormone. T4 only becomes useful to the body after one of the D1 or D2 deiodinase enzymes converts it into the biologically active T3 hormone. Another deiodinase enzyme (D3), is able to convert some of the T4 into reverse T3 (often shortened to rT3). T3 cannot be converted into rT3.
The deiodinase enzymes can be upregulated or downregulated depending on the need to increase conversion from T4 to T3 or reduce it, and increase or decrease rT3 (in order to manage T4 clearance).
The conversion process of T4 to rT3 occurs on an on-going basis within the cells, in order to clear excess levels of T4 from the body. RT3 is eventually broken down by other enzymes and converted into T2, which in turn is converted into T1. T2 and T1 are simpler molecules with fewer iodine atoms. The body then eliminates these molecules within roughly twenty-four hours. A spin-off takeaway from this post is that even on T3-Only therapy the body does create T2 from T3 (having T2 has always been an argument for using desiccated thyroid by the pro-NDT camp - but it isn't an issue if just using T3 therapy).
RT3 is an isomer of T3, which means that it has the same molecular formula as T3, but the atoms form a slightly different internal structure. RT3 is very similar to T3.
It is the D3 deiodinase enzyme that converts T4 to rT3. This is important to be aware of because high levels of D3 deiodinase enzymes can block the T3 hormone from connecting with thyroid receptors in the cell nuclei.
Elevated rT3 is a marker of slower metabolism. Some doctors say rT3 is metabolically inactive but research has shown that this is incorrect. Elevated rT3 does indeed reduce the number of D2 deiodinase enzymes that are present. Because it is D3 deiodinases that convert T4 to rT3, very high rT3 is a likely marker that these D3 enzymes may be interfering with T3 action in the cells (even though it is not rT3 that does this directly). So, high reverse T3 is a marker of T3 being blocked in both ways - through lower conversion (less D2 deiodinases) and blocked T3 (high D3 deiodinases).
RT3 exists in order to provide a dynamic mechanism to match the amount of available T3 to the body's needs. RT3 also provides a mechanism for slowing down the metabolism in the event of starvation, serious illness or high stress, and in these circumstances the conversion rate of T4 to T3 decreases and more rT3 is made. As rT3 increases it also reduces the effect of FT3 through the D3 deiodinases. The reduced T3 level that occurs during illness, fasting, or stress slows the metabolism of many tissues. Because of the slowed metabolism, the body does not eliminate rT3 as rapidly as usual. The slowed elimination from the body allows the rT3 level in the blood to increase considerably.
Some studies show that most people convert over 50% of their FT4 to rT3 and therefore, they convert less than 50% of FT4 to the metabolically active hormone FT3. The levels of reverse T3 fluctuate up and down through the day. There is no ideal level for rT3 or any perfect ratio of FT3 to rT3.
The late Dr. John C. Lowe provided some excellent information on reverse T3 and whether it can actually be used to diagnose hypothyroidism during a telesiminar with Bette Dowdell on 29 December 2010:
"... I’m never confident of coming to a conclusion that someone has a problem with high reverse T3, not unless the person has had multiple measures of the reverse T3 over a 24-hour period. Like the TSH, free T4, free T3, reverse T3 levels vary dramatically every 30 minutes or so. Depending on when a person’s blood is drawn or saliva taken. Sometimes the levels will vary enough so that a clinician will give the patient a different diagnosis from the one that he or she would have given 30-minutes before or after the blood or saliva sample was taken. So blood levels vary rapidly. Because of this, I don’t believe the reverse T3 or the other lab tests in general are very useful. However, I do believe the reverse T3 is useful under one circumstance: when we have enough measures to get averages over time, and when the levels are regularly way out of range. So, in my view, the reverse T3 can be useful, but I think its usefulness is limited, which is true of the TSH and other thyroid hormone levels."
There are many conditions that can upset the balance of T3 and reverse T3. These include: iron issues, taking too much T3 with T4, poor conversion of T4 due to lack of important nutrients like selenium, infections, tumours, damaged heart muscle, aging, chronic alcohol abuse, diabetes, liver disease, kidney disease, severe illness, stress, surgery, a number of drugs, genetic defects affecting deiodinase enzymes (DIO1 and DIO2 gene defects), or other key components that may affect the pathways involved in thyroid hormone metabolism. Many more issues may be added to this list over time.
Once a decision has been taken by a doctor and patient that it is time for the patient to have a trial of T3 replacement therapy, the decision has been taken that T4 based medication should no longer be the predominant thyroid hormone being used. After this decision there is little point having any real interest in reverse T3, as correct titration of T3 thyroid hormone can only be done well using symptoms and signs.
Consequently, I believe the only real scenarios where rT3 may have some use are in treatments that are predominantly T4 based, i.e. with T4, T4/T3 (where only small amounts of T3 are used), or natural desiccated thyroid replacement therapies. I believe that in predominantly T4 based treatment, rT3 may be useful to assess. If a patient using natural desiccated thyroid, or T4, has very high rT3 levels, this does suggest that the treatment is failing. This failure may be due to the unsuitability of the particular thyroid treatment for that patient, or due to something else like low iron or low cortisol levels. But the rT3 test would illuminate the problem at least. However, it is important to remember that in some cases rT3 may appear normal and yet the patient still may have problems with T4 thyroid hormone, and the rT3 interfering with the biologically active FT3.
Note: I do not believe that any particular level of rT3 or any ratio of FT3/rT3 is important. It is only a guide and has to be put into perspective with patient symptoms and signs being the most important focus.
I hope you found this helpful.
(Updated in December 2019)