Reverse T3, also known as rT3, is a possible marker of poor conversion and potentially blunted T3 action. This makes it useful to test for in some cases.
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. Only T4 can be converted into rT3.
The deiodinase enzymes can be up-regulated or down-regulated 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 ongoing 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. T3 is also converted into T2 and then into T1. So, even on T3-Only therapy, the body creates enough T2. Natural desiccated thyroid (NDT) users often cite the T2 content of NDT as being an advantage over using T4/T3 – but it is not. You get all the T2 that you need from T3 medication.
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. For those who have a working thyroid, or are on medication containing T4, rT3 is a natural bi-product because the body needs a way to clear excess T4. So, having rT3 is natural and is not necessarily a bad thing.
Let me be very clear rT3 cannot bind to any thyroid receptor. RT3 itself does not block T3. There is no particular level of rT3 that is suddenly a special concern. RT3 does not have to be below mid-range. There is no FT3 to rT3 ratio that is either bad or good. There is much information out on the Internet that is clearly very incorrect with respect to rT3. However, this does not mean that excessively high rT3 cannot indicate a problem – because it can.
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 could inhibit some of the T3 hormones from connecting with thyroid receptors in the cell nuclei. For this reason, only, elevated rT3 could be a potential marker of slower metabolism. Some doctors say rT3 has no importance at all but research has shown that there is value in assessing rT3 under some circumstances. Elevated rT3 does indeed slightly reduce the number of D2 deiodinase enzymes that are present. Moreover, because it is D3 deiodinases that convert T4 to rT3, very high rT3 can be a 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 can be a marker of T3 being blocked in both ways – through slightly lower conversion (less D2 deiodinases) and blocked T3 (high D3 deiodinases). Note: the words ‘can be’ in the last sentence. You have to look at the complete picture with the thyroid lab test results and especially at the clinical presentation of the patient (signs and symptoms).
See this research paper that shows that reverse T3 (rT3) is a T3 blocker and not an inactive metabolite:
“Qualitative and quantitative differences in the pathways of extrathyroidal triiodothyronine generation between euthyroid and hypothyroid rats.”. J E Silva, M B Gordon, F R Crantz, J L Leonard, and P R Larsen 10.1172/JCI111313 https://www.jci.org/articles/view/111313
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. 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 deiodinase enzymes. 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.
Having said all the above, it is obvious to me from my own experience and from working with thousands of thyroid patients that a few thyroid patients can not tolerate T4 medication and even low levels of rT3. This cannot be determined from laboratory test levels of rT3 or FT4. It has to be determined based on the symptoms and signs of the patient during treatment. These patients need to be on T3-mostly or T3-only therapy.
The late Dr. John C. Lowe provided some excellent information on reverse T3, and he talked about whether it can actually be used to diagnose hypothyroidism:
“… I’m never confident of coming to the 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 is 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, ageing, 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 in having any real interest in reverse T3, as correct titration of T3 thyroid hormone can only be done correctly by 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.
In predominantly T4 based treatment, rT3 is still useful to test.
If a patient using natural desiccated thyroid, or T4 medication, even in a combination with T3 and their symptoms are not improving with medication increases, then checking rt3 as well as the other thyroid labs of TSH, FT3 and FT4 can be very insightful.
So, what should a patient who is on T4 based medication or a T4/T3 combination be on the lookout for with respect to rT3? Well, having T4 go into a lot of rT3 can mean the T4 isn’t converting into the necessary level of FT3. Only improving FT3 level tracks with the improvement of symptoms.
Consequently, for someone on T4 or T4/T3 (including NDT), they need to be assessing:
1) does the FT3 level increase AND
2) do they feel their symptoms and signs have improved?
If either FT3 does not improve OR symptoms and signs do not improve then any rising rT3 may signal a conversion issue.
This assessment can be made whether the T4 or the T3 has been increased in any T4/T3 combo. Testing rT3 can help in making the assessment.
Any issues with the conversion of T4 to T3 could be due to the unsuitability of the type of thyroid treatment being used or due to something else like low iron or cortisol levels.
Note: in many cases, the type of thyroid treatment being used is limited in its success simply because a doctor fails to increase it to a high enough level because the TSH is low or suppressed. This is frequently a huge mistake because the patient is neither over-medicated nor hyperthyroid. This is a very common error and it stops many thyroid patients from recovering.
It is important to remember that in some cases rT3 may appear normal and yet the patient still may have problems with processing the T4 thyroid hormone and getting sufficient T3 hormone. RT3 can only provide some additional insight.
RT3 is only a guide and has to be put into perspective with patient symptoms and signs being the most important focus, along with how FT3 changes with changing treatment.
I hope you found this helpful.
Best wishes,
Paul
(Updated in December 2019)
Hi Paul. I am hypothyroid due to Lyme disease and having a very difficult time getting symptom resolution. I have tried T3 only and NDT. And I have gone to very high doses with both. I do best on NDT until eventually I start getting worse. At this point I check my reverse T3 and if is high. Since I don’t feel as good on T3 only, I was thinking maybe I should try a combo therapy with mostly T3 and modest T4. What do you think? Also, what is the most NDT you’ve seen someone need? 10 grains? More? Same question for T3 only: what’s the highest dose you’ve seen needed? Thanks.
Hi Michael,
Lyme disease makes things much more difficult.
The people I have worked with who have Lyme tend to be poor converters and do better with T3 only.
Did you use the slow and steady multi-dose protocol for using T3 that I discuss in Recovering with T3?
Did you also test cortisol properly with both a saliva cortisol test and an 8-9 am morning blood cortisol test? Lyme often causes low cortisol and makes it very difficult to tolerate any thyroid meds or get the right response to them.
Treating the Lyme properly is essential – you’d have to seek expert advice on this as it isn’t my area.
T3 doses required ought to be assessed using symptoms and signs – talking about specific numbers isn’t useful as people vary so much.
I would definitely assess the cortisol situation as this can change the way you are using T3 (see the Recovering with T3 book for more details).
Making sure the Lyme is getting totally eradicated is also important – this can be very difficult.
Best wishes, Paul
Hi Paul. Thanks for the fast response. I have all my cofactors — cortisol, iron, etc. — well managed at this point, after much research and experimentation. Unfortunately with cortisol, the circadian method didn’t work for me. So I supplement cortisol. I do still take my first dose of thyroid, be it NDT or t3 depending on the protocol I’m trying, early in the morning. I have tried the slow and steady multidose t3 method from your book several times now. But I have found I have to increase eventually to very high doses, up to 300 mcg, and still I never get complete symptom resolution. My main symptoms unfortunately are mental. In particular I fight severe, suicidal depression symptoms. So I am very motivated. And I have done much research, including reading your books. I marvel at the research you did prior to the Internet. You are a hero to me because I have been fighting terrible symptoms for years, and I know you did and now share your knowledge with others like me. By the way I am writing from the middle of Texas.
I assume you’ve checked B12 thoroughly when not had any B12 supplements for several months?
Check red blood cell count and mean cell volume on a full blood count too. Low cellular B12 can cause severe depression.
Multi-dosing ought not to need individual doses of 300 mcg – if that’s what you meant.
I’m not sure what else to say Michael.
Good luck to you!
Paul
Hello, I wonder if you can advise please?
I have suffered with ME/CFS for 30 yrs. In 2017 I had half my thyroid removed due to cancer. No further treatment required. My health continued to deteriorate and I “crashed” in 2019. In 2021 I had a Genova test and my TSH was slightly raised -3.57 – (although considered normal) and I had high levels of both antibodies. My private GP put me on Novathyrol (75mg) and I also took a saliva cortisol test and take 10mg DHEA and 100mg Pregnenelone daily.
A follow-up blood test resulted in improved TSH, T3 and T4 remained in range although towards the bottom but RT3 was elevated and antibodies remained high. As a result I switched to T3 (Liothyronine 20mg), she said I needed to get the RT3 down. My TSH has now gone up again to original levels, my T4 is below normal and my T3 is at the bottom of the range. My antibodies are coming down but my RT3 has remained high. My Private GP has moved out of the area and I am not feeling any better – in fact I haven’t really progressed since I began treatment a year ago, in some ways I may be worse.
Reading this article I am wondering if we really needed to have worried about the RT3 in the first place or should we focus on the adrenals/cortisol levels and managing the Hashimotos? (Iron levels have been checked and are fine I believe.)
Many thanks and apologies if this is not appropriate – please delete if so.
Sarah, what you haven’t said is whether you actually have symptoms. Some people are okay with levels of FT3 that would make others feel ill.
So, I would need to know if you have hypothyroid symptoms. If you do then you aren’t on enough T3. Taking enough T3 will always ensure FT3 goes up and rT3 goes down if the person is not taking too much T4 medication. But there is no need to change anything unless you are symptomatic. Going by labs alone is not sufficient.
Best wishes, Paul
Dear Paul
Thank you so much for responding, yes I definitely have symptoms. I will keep preserving.
Many thanks.
Best wishes
Sarah
I wouldn’t persevere, I would test the active, free hormone Free T3 (FT3).
Focus on the scientifically important thyroid level and assess whether supplementation with thyroid hormone (and what sort of thyroid hormone) is the right thing to do. Ideally, you would test TSH, FT4, FT3 and reverse T3 (rT3). But FT3 is key.
Best wishes, Paul
p.s. my The Thyroid Patient’s Manual book really explains why my answer is so relevant.
It is a practical guidebook to getting thyroid issues sorted out.
What I don´t understand is this: rT3 is said to act as a metabolic break when the body needs to slow down and preserve energy, for instance, in illness, during periods of extreme stress, or due to severe calorie restriction. The need to preserve energy would explain why hibernating bears have very high levels of rT3.
If that is indeed correct, then why is rT3 inactive and unable to block T3 to slow down metabolism?
In a euthyroid person with high rT3, does that only mean that less T4 is converted to free T3 and more to rT3 and this in turn slows down metabolism? And, in a person on T3+T4 or NDT, that the T4 is converted to more rT3 than FT3, but that the additional T3 from the drugs is not affected? So, a person on a synthetic combo or NDT could in theory remain euthyroid thanks to the extra T3 s/he is taking?
I have also read that rT3 only stays in the body for a few hours before being converted to T2, which is why it does not have time to pool. It is also stressed that levels vary a lot throughout the day. But even if that is true, I imagine new rT3 is made all the time in people with severe illness, high cortisol, inflammation, or on strict diets, etc. So, does that not mean that new rT3 is constantly created, which can have adverse effects on metabolism?
Or is the theory that rT3 only exists to dispose of excessive T4, and does not affect FT3 at all?
I didn’t say this exactly Anna.
In the case of saving energy during illness or even hibernating bears what is happening is a lowering of FT3 and an increase of rT3. The T4 that people (or even bears) have is no longer going into so much FT3 but is going into a lot more rT3. It is the lowering of the FT3 that is really having the effect, with a much more minor effect of the D3 deiodinase that converts to rT3.
In the case of people on thyroid treatment especially a mix of T4/T3 then what they have to look out for is that the T4 content isn’t so high that it is failing to produce enough FT3 but going into a lot of rT3. I’ll leave you with a blog post link on that shortly.
There is much misinformation on the Internet – the entire idea that rT3 blocks receptors to FT3 is nonsense.
I think this blog post will help you:
https://paulrobinsonthyroid.com/more-t4-t3-thyroid-medication-might-not-always-raise-patients-ft3-levels-in-thyroid-hormone-treatment/
On T4 treatment or T4 / T3 treatment assessing rT3 is still helpful as it indicates how well the T4 component is converting. But the idea that rT3 is just blocking the T3 from working totally is wrong. The D3 deiodinase enzyme has some limiting effects on the activity of T3 in the cells but it isn’t a massive effect.
Hope this helps. Although I’m not sure what problem you are trying to solve.
My The Thyroid Patient’s Manual book might help a lot also.
Best wishes, Paul