Thyroid Blood Tests Part 5 - What is Reverse T3?

T4 is a metabolically inactive hormone. It only becomes useful to the body after an enzyme called 5’-deiodinase converts it into the active hormone, T3. A different enzyme, 5-deiodinase, is able to convert some of the T4 into reverse T3 (often shortened to rT3).

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.

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 but it is not biologically active.

Like FT3 and FT4, rT3 may enter the cells and bind to the thyroid receptors in the cell nucleus but it is unable to trigger any metabolic effects. If too much rT3 is produced then it may have a negative effect on metabolic rate and the regulation of cellular function.

RT3 exists in order to provide a dynamic mechanism to match the amount of available T3 to the body's actual 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. 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 ideal 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."

For a full transcript of the interview with Dr. Lowe see: http://toopoopedtoparticipate.com/blog/dr-john-c-lowe-speaks/

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, some drugs, genetic defects affecting deiodinase enzymes 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 then 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 at the present time.

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 in a lot of cases. If a patient using natural desiccated thyroid or T4 has very high rT3 levels then 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 competing for the thyroid receptors with the biologically active and more important FT3.

I believe that far more research is needed regarding the natural hormone rT3 and what conditions can cause elevations in its level and whether it is possible to use it in practice for diagnosis or treatment.

My best regards,

Paul