Explaining Reverse T3

[Sailing14]

Could someone explain in more detail what this is and why it happens? Also, the symptoms.

Thank you.

[tattybogle]

yes ...

but apparently i've got to go and fry some pakora's to stop somebody else doing it and filling the kitchen full of smoke .....

if you're still inthe dark after dinner i'l tell you then

[tattybogle in reply to tattybogle]

Ok i'll have a bash :

T4 can either be turned into T3 by removing one iodine atom from one place .

or it can be turned into reverse T3 by removing one iodine atom from a different place.

T3 is 'active' , it is what makes our cells 'do' their thing .

Reverse T3 is not .... it cant fit into T3 receptors inside the cells, so it can't make them 'do' anything .

The decision to make T4 into T3, or Reverse T3 ,is made by the deiodinases which are partly controlled by how high/low the T4 level is ,... partly controlled by how high/ low the T3 level is .....and partly controlled by the TSH level.

This process is constantly adjusted by the body , Reverse T3 is part of the normal healthy functioning and balancing of our thyroid hormone regulating system , There is nothing to worry about with having some reverseT3....it is supposed to be there ,

Reverse T3 is then 'recycled' by the body first into T2 then T1 (as a way of recycling the iodine... T4 is 4 iodine atoms .. T3 is 3 iodine atoms.. T3 is 2 and T1 is 1)

One way of looking at Reverse T3 is that it is a sort of 'safety valve' to get rid of 'too much' T4

There is a 'normal' range for Reverse T3 .. level s within this range are not a concern.

If Reverse T3 is over range there can be a multitude of reasons for it ,

only one of them has anything to do with our thyroid hormone levels... if fT4 is too high for us, then high Reverse T3 is the consequence .

I've forgotten what the many 'other' causes of high reverse T3 are , greygoose has written several excellent replies on the subject , if you look up her previous replies on her profile page you will find them, or she may pop up to reply here ( i hope she does , we've been missing her expertise lately )

As far as i know , Reverse T3 doesn't ' do ' anything .... it just is...but that is an oversimplification.

i think radd has more understanding than me about what high reverse T3 means in regard to thyroid hormone function and conversion of T4 to T3

[Sailing14 in reply to tattybogle]

Thank you for your very detailed response. I am reading over it now and will look into the links too that you also kindly included.

[radd in reply to tattybogle]

Sailing14

Well, you can’t summarise it in a few sentences 😉. 

There are three deiodinase enzymes, D1, D2, D3 which act like control points dictating whether thyroid hormone is activated or deactivated. D3 is the one responsible for RT3. Just as we require a certain ratio of FT4:FT3, we also need FT3:RT3. When symptoms and/or labs signify a problem it is not the RT3 itself but the converting deiodinase enzyme D3 which when over-stimulated brings about negative repercussion, even impairing further healthy FT4-FT3 conversion. 

There are numerous causes for D3 over-activation such as the inflammation seen in severe illness and autoimmune conditions, constant calorie deficit or obesity, or by medicating excess thyroid hormone meds when the body will congruently covert T4 to RT3, and T3 to an inactive form of T2 called 3,3′-T2 as a safely protection measure. Some RT3 will metabolise further to T2 and other inactive metabolites whilst a tiny bit is pee’d out.

Another deiodinase enzyme D1 helps to clear RT3 from the blood but the higher RT3 becomes, the more FT3 lowers in a sea-saw fashion and this lowers D1 activity, so decreasing the ability to remove excess RT3. Also as T4 rises (even within range) conversion of T4-T3 reduces in another seesaw fashion in a process called ubiquitination involving the inactivation of D2. Low D2 also loses some RT3 conversion efficiency leaving what is there hanging about and reducing T3 levels further.

High RT3 can occur with high FT3 levels but the high RT3:T3 ratio is more widely recognised in ‘low T3 syndrome’ (non-thyroidal illness syndrome) or just non-thyroidal illness as it occurs in people with both a healthy thyroid or absence of thyroid. It is this association between high RT3 and illnesses and/or hypothyroid symptoms that incorrectly invited thought that RT3 hindered T4-T3 conversion, blocked T3 transport into cells and plugged receptors, and you can still read this in many articles. 

However, latest research shows it to be the action of D3 that allows the transport of T3 into the cell but then takes T3 apart before it reaches the receptors in the cell nucleus and mitochondria rendering it inactive. Therefore, there might be a period of time where hypo symptoms occur although labs still show adequate amounts of  FT3 in the blood stream before eventually they plummet. 

High D3 activity risks deactivating our meds and the symptoms are felt as anything hypo. Symptoms may even occur in the presence of low RT3 (when there is not enough T4 to convert) as if conditions are right to activate high D3, efforts become concentrated in reducing T3 (as above). As we know T3 is the active hormone that achieves wellbeing.

All three deiodinases influence each other by levels and behaviours. Because thyroid hormones are transported on proteins they are vulnerable to other hormonal changes and effected by a multitude of biological factors, and this is why having RT3 levels measured is so immensely difficult to interpret. Everyone’s baseline of med needs, life style and health conditions are different, constantly changing and will reflect in the levels and sensitivity of thyroid hormone transporters and receptors.

Testing RT3 is expensive and time consuming. I’ve previously tested mine but only as a primary evaluation of reasoning for remaining so symptomatic and desperate whilst medicating supposedly adequate meds for several years. I don’t think you can use results for titivating thyroid meds unless to reinforce suspicions of over-medication in the absence of inflammation. 

The aim for hypothyroid peeps is not only to medicate the correct amount of thyroid hormone but to get the hormones working effectively in alleviating symptoms with the right deoidinase activity and supports in place. When symptomatic it is better to use labs to view the intracellular T3 loss caused by possible elevated RT3 (just assume it is there). Treatment is everything as advocated on the forum:

- Keep thyroid hormones optimised to your individual sweet spot (ranges are a useful guide).

- Optimise essential nutrients/iron. 

- Ensure gut issues are dealt with whether this be eradicating infection, adopting a  g/f diet, and/or adding HCI/digestive enzymes, etc. 

- Consider a DIO-2 genetic polymorphisms and add T3 meds if appropriate. 

- Support adrenals and sex hormones if required.

[radd in reply to radd]

This pic courtesy of Tania Smith shows RT3 (empty pink circles) inside the cell with T3 (solid pink circles). RT3’s main aim is to stop T3 from entering the nucleus to become active, by converting it to another hormone before it gets there (not blocking or plugging the receptor as RT3 lacks an iodine atom at a key position on the molecule disabling it from binding to the nuclear receptors.). The more active D3 is in making RT3, the more T3 gets crowded out. Only T3 can enter the actual nucleus and there is also thought that when the receptor is left unoccupied for a long duration it can desensitise.

More info at .... thyroidpatients.ca/2019/11/...

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[tattybogle in reply to radd]

Thanks so much for that lovely explanation radd

I can understand 'deiodinase'..... but i can't 'speak it ' yet

[Auders in reply to radd]

oh my goodness! You have completely blown my very foggy brain!😄

[Hidden in reply to radd]

so radd is it that STTM are saying rT3 is cause, HU et al. Are saying it is effect?

[radd in reply to Hidden]

dfc,

Yes, STM used to talk (maybe still does?) about RT3 plugging T3 receptors because high RT3 and low T3 occur together, but RT3 are a different shape and wouldn’t fit into a T3 receptor.  We also need a certain amount of RT3 to maintain brain and peripheral tissue euthyoidism but STTM demonised it as a very negative hormone.

RT3 is a consequence of D3 (deiodinase type 3 thyroid hormone deactivating enzyme) and which when excessively unregulated creates high levels of RT3 but also many other spiralling negative actions. It is an up regulation of D3 that can impair our thyroid hormone meds from working so well.

If you want to learn more about RT3 you need to understand how the three deiodinases (enzymes that activate and deactivate thyroid hormone) change in response to differing physiologic conditions but are also influenced by each other. This complex set of workings is required to ensure different tissue levels of T4 and T3. Otherwise we would be flooded in some areas (hyper) and deficient in others (hypo). eg T3 is not only influenced by how much meds we take but activity of the tissue deiodinase D1, D2, D3.

T4 is made up of four iodine atoms and all three deiodinase work by removing atoms selectively to create T3 or RT3 (both three iodine atoms). Further deiodination works to create T2 (two iodine atoms). Selenium is a major component of the deiodinase and why so heavily promoted on the forum.

After thyroid hormones are made they are bound to transport proteins until reaching the cellular membrane where they become free. Whether they are activated or deactivated is dependant not only on our metabolic demand but factors such as nutrient deficiencies, obesity, illness, calories deficit, etc . Positive health attributes such a clean diet and good sleep have a positive effect on the deiodinases. D1 and D2 create T3 (although through different mechanisms), and D3 creates RT3.

Most scientific papers are tricky to understand but I recommend you look at Tania Smith blogs that are truly fascinating, and come with pictures 😬. 

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Deiodinase Type 3, not RT3, plays the T3-blocking role thyroidpatients.ca/2019/11/...

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Reverse T3 in the context of health status, dosages, and thyroid levels

thyroidpatients.ca/2020/11/...

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RT3 inhibits T4-T3 conversion. How worried should we be?

thyroidpatients.ca/2019/11/...

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Think twice about cancelling patient-pay Reverse T3 tests

thyroidpatients.ca/2020/02/...

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Deiodinase Type 3, not RT3, plays the T3-blocking role

thyroidpatients.ca/2019/11/...

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Meet deiodinase type 1 (D1): The philanthropist enzyme

thyroidpatients.ca/2021/02/...

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Principles and Practical tips for Reverse T3, FT3, FT4

thyroidpatients.ca/2019/11/...

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A complete pathway map of T4 and T3 metabolism and clearance

thyroidpatients.ca/2021/08/...

[Hidden in reply to radd]

thanks Radd, will add those resources to my list! If we need rT3 for brain, do you think those on T3 only are running a risk of their brains being negatively impacted?

[radd in reply to Hidden]

dfc,

For those on T3-only, D3 will still convert excess to an inactive form of T2 independent of T4 metabolising to RT3, which is controlled by neurones that degrade excess. Other control mechanisms I know of are the bi-directional binding proteins, and cell and thyroid hormone specific cell membrane transporters. There must be multiple other ways the body controls levels of thyroid hormone control but after the basics, its all a bit beyond me.

We have more T3 receptors in the brain than anywhere else, and T3 is actually a neurotransmitter in its own right. When I started T3 meds I had pops and whooshes and effervescent bubbles going off for about two years that no-one could explain but I think it was a near life time of hormone starved receptors waking up. 

Just found this pic depicting D3 stopping T3 from entering the cell's nucleus.