An hypothesis about RT3 – did you know you might have a hidden pool of it?

arrowEveryone makes Reverse T3 (RT3)–an inactive thyroid hormone. It’s a way to clear out excess T4 when your body isn’t needing that extra storage hormone. i.e. instead of the T4 converting to the active T3, your body (and specifically your liver), will convert it to RT3. If someone without a thyroid problem gets the flu, up goes the RT3 to conserve energy. If someone has a bodily injury, up goes the RT3 to conserve energy.

And thyroid patients seem to see their RT3 go up in the presence of low iron or a cortisol issue.

But if you think about it, why doesn’t it go down faster when we decrease our T4? T4 has a half life of one week, yet it can take 8 – 14 weeks for RT3 to go down. Hmmmmmm…

Thyroid patient Sebastian from Germany sent me this information about Reverse RT3 that I find fascinating. What do you think?

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I’m studying biology and chemistry and have Hashimoto’s Thyroiditis with high RT3. I just wanted to inform you about an interesting idea/hypothesis I have found.

There seems to be a “hidden pool” of RT3 in the human body. This RT3 pool can increase in size while enough T4 is available, and then secrete RT3 in times where the body needs it but hasn’t got enough T4 to produce it via deodination (the removal of an iodine molecule).

“It is concluded that a hidden pool of RT3 production exists in vivo in man.”
“It would appear that hypertrophy of this hidden pool of rT3 production occurs in high T4 states […]”

Source: LoPresti et al., “Does a hidden pool of reverse triiodothyronine (rT3) production contribute to total thyroxine (T4) disposal in high T4 states in man.”, J Clin Endocrinol Metab. 1990 May;70(5):1479-84. http://www.ncbi.nlm.nih.gov/pubmed/2335581

I have made observations regarding  my own thyroid blood tests and the blood tests of other patients that seem to support this hypothesis. I have been on T3-only for 6 weeks now, started with an RT3 of 330 pg/mL at approx. day 0, and now have measured a RT3 of 685 pg/mL (twice as much!), even though my TSH is low, FT4 has fallen rapidly to 0.5 ng/dL, and no T4 medication has been taken for full 6 weeks.
Another patient I know has also made interesting correlations between FT4 and RT3. He isn’t on T3-only, but observed a time-delayed (!) correlation between both values – which could be interpreted as an indicator for the presence of an RT3 storage pool in the body, that grows when enough T4 is available, and sets RT3 free in times when there is less T4 available.

I also found studies which found that RT3 has a 1000 times less feedback on the TSH than T3 has, and 100 times less than T4. This could explain any differences between TSH and symptoms, as the “RT3-system” seems to be almost completely isolated from the thyrotropic regulation system (the latter is that which directly influences the secretory activity of the thyroid gland).  RT3 can obviously rise and fall without having (almost) any effect on the TSH.

Source: Cettour-Rose et al.: “Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats”, European Journal of Endocrinology (2005) 153 429–434.

In combination, this could explain why the clearing process of RT3 takes approx. 8-14 weeks, although T4 has a plasma half-time of only 8 days, and rT3 only 4.5 hours!

The intracellular T3 receptors aren’t “clogged”, and then suddenly become free after that period of time has elapsed. Instead, RT3 is a competitive inhibitor of T3, meaning it constantly goes in and out of the T3 receptor. You probably know that already.

Patients report feeling well with T3 only dosages of approx. 80-120 µg T3 per day. According to Celi et al., 2010, this would be equal to 240-360 µg of T4. I always wondered why they don’t end up feeling hyper.

This all makes sense now under the assumption that a hidden RT3 storage pool exists somewhere in the body. Although there is no new T4 being produced or taken in, and although the remaining T4 and RT3 have both decayed rapidly after one starts with the T3 only method, there is still alot of RT3 being set free by the storage pool all the time. This storage pool might be big enough to last for several weeks to months. Since RT3 is the competitive inhibitor of T3, this might be why patients are able to tolerate (and even need) so very large amounts of T3.

Then, after the storage pool has been emptied, the remaining RT3 rapidly decays because of its short half-time and no new RT3 can be produced because no T4 is available in the body. Therefore, RT3 concentrations within blood and cells drop. Thus, the competitive inhibition gets a lot weaker at that point, and patients start feeling hyper because the same amount of thyroid hormones (T3) is now significantly increased in its effect, since it can stay much longer in the T3 receptors without being competitively inhibited (kicked out of the receptors) by RT3.

This process of totally emptying the RT3 storage might occur very quickly, therefore the drop in RT3 concentrations is very suddenly, all of which might happen within several days. And this is why patients then get hyper and have to reduce their dosage to half or less of what they’ve taken previously over the 8-14 weeks.

“Clogged receptors” don’t make sense because RT3 is a competitive inhibitor, capable of traveling in and out of the T3 receptor all the time.

“Clearance” occurring after 8-14 weeks, although both educt (T4) and product (RT3) have significantly (!) shorter lifetimes, doesn’t make sense either.  Neither does a totally defective TSH lab test, because in principle, it worked fine for all the patient’s lifetime before they got their thyroid disease; and because significant correlations between TSH and FT3 and FT4 can be observed.

This all makes sense to me now, based on two assumptions:

1. While T3 and T4 have a strong negative feedback effect on TSH secretion, RT3’s effect on the TSH secretion is minimal, being about a thousand times smaller in effect than that of T3, and about a hundred times smaller in effect than that of T4….as described in the study of Cettour-Rose et al., 2005, mentioned above.

2. The body has a large, previously unknown storage for RT3. This storage can grow while enough T4 is available, and the storage’s content can be set free when needed. As described in the study of LoPresti et al., 1990, mentioned above.

I hope you can use this information for further research. Thanks for reading.

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48 Responses to “An hypothesis about RT3 – did you know you might have a hidden pool of it?”

  1. OM

    Very interesting,…..wonder what the purpose of an RT3 pool might be and whether or not we should be trying to reduce it by taking T3 only? Usually the body knows what it is doing….do we?

    If RT3 can move in and out of T3 receptors and can produce T3 when needed, maybe it is a backup in case of problems with T4 to T3 conversion. If RT3 doesn’t “block” T 3 receptors as we thought is our assumption that RT3 is harmful really the case? Looking forward to learning more about this.

    Reply
  2. carol

    If you take only T3, can T3 be converted to RT3??

    Reply
  3. Jennifer

    Fascinating reasoning! What if this hidden pool is actually in the thyroid gland? Nah…it’s probably in the gut where everything else seems to be these days. I hope the author continues research on this topic. I love researchers who also have hypothyroidism!

    Reply
  4. Elenor

    Very very interesting. This might also explain why a higher (and higher) dose of T3-only has not led to even the slightest hyper symptoms at all? (Alas, been hopin’ for the weight-loss one! {wink}) If this hidden store is competing with the T3 ingested, then keeping the ingested T3-only high(er) (to ‘push down’ the internal T4 production) should (should?) allow the hidden cache to empty (over the 8-10 weeks or longer)?

    Reply
  5. Sebastian

    Hey folks,

    first of all, rT3 does not “block the receptors” in the way many texts on the internet suggest. The mechanism by which rT3 acts is called “competitive inhibition” and should be taught at any biology class in school. The principle is, that both T3 and rT3 fit into the T3 receptor (which is located nearby the DNA in every body cell’s core), but while T3 creates a reaction while sitting in the receptor, rT3 does not (it just fits, but does nothing except sitting there). Now, what must be understood is, that this is a *dynamic* system. It is, by all means, not static. The T3 and rT3 molecules always fly around in the cell’s core, sometimes they enter the T3 receptor, sit there for a while (very short time!), and then leave it again. This process of entering, staying and leaving is very quick, meaning fractions of a second, but it happens very often. Both T3 and rT3 “jump in and out” of the T3 receptor all the time. And by means of statistic, the more rT3 there is in relation to T3 (= the lower the T3/rT3 ratio *in the cell* is), the longer the T3 receptor gets blocked by an rT3 molecule, the shorter the time is when there is a T3 molecule in the receptor, and consequently the weaker the T3’s effect as a hormone is.

    As you already know, T3 only has an effect while sitting in the T3 receptor. You can have a shitload of T3 in your cells, it wouldn’t matter unless they were able to temporarily bind to the T3 receptor. Only while sitting there, these T3 molecules trigger a hormonic response/effect in the body. That’s what you understood and know already. Now, you just have to imagine this process being dynamic, meaning T3 and rT3 constantly jumping in and out of the receptor, like a battle for who gets to sit in there. And the effect that the thyroid hormone T3 has, is then determined by the statistical length of time that the receptor is inhabited by a T3 molecule, and the statistical length of time that the receptor is inhabited by an rT3 molecule. Which is exactly the reason why the ratio between T3 and rT3 can be used as a means of measurement for T3’s real activity as a hormone in the body (somewhat insecurely though, because these values are derived in the blood, not in the cells).

    This mechanism of “competitive inhibition” is long-known and well understood. I learned about it when I was in school. You can easily look up in literature, that rT3 is the competitive inhibitor of T3. Therefore, the concept of rT3 “clogging the receptors” and then suddenly clear them after about 8-14 weeks, didn’t make sense to me, and I began to investigate other possible explanations for this observed behaviour. This when I stumbled upon the study of LoPresti et al., described in the blog post above, in which the authors state the hypothesis that a hidden storage pool of rT3 may exist in the human body. Hopefully, this sheds some light on why the concept of “clogged receptors” does most certainly not apply; because rT3 doesn’t have the ability to permanently bind to a T3 receptor. It can only bind for fractions of seconds before being released again, as can T3, but they both can bind again shortly after that, resulting in a constant “battle for the receptor”, between one hormone that is biologically inactive, and one that is biologically active, therefore resulting in what is called competitive inhibition.

    The storage pool itself may be (and that’s just an idea from me) an evolutionary advantage for the human body, since it helps with shutting down the body’s metabolism when such an action is required. For example, after a totally exhausting exercise (running until you cannot run anymore etc.), a quick shutdown of the metabolism was a big advantage for survival, because it forces one to sit down and relax, thereby saving energy and forcing the body into regeneration. Other, not so imminent scenarios may be sudden temperature changes or changes in food availability, or illness.
    Having a huge storage of rT3 (maybe in the liver? who knows) would have been a huge advantage for survival in such scenarios, because the body could simply release the already existing large amounts of rT3, which is quick and costs almost no energy. This would have been a much more efficient way than having to produce these amouts of rT3 by deiodination (T4 –> rT3), which in comparison is a much slower process, plus this process is being further slowed down if T4 levels were dropping, which can be observed e.g. after doing sports. The less T4, the longer it takes to produce the same amount of rT3. It would be much more efficient to just have a storage of rT3, fill it up in times where more than enough T4 is available, and then just release it when neccessary. From an evolutionary point of view, humans with this storage (or other animals; the thyroid is very old in comparison with the dawn of our own species!) would have had a big advantage over those who don’t, thereby distributing their genes for the rT3 storage very widely through the whole population by means of natural selection. Just a thought where it may come from. Remember, even frogs need T4 to induce their metamorphosis, the thyroid is “historically” very old in the tree of life, and therefore such things would have potentially hundreds of millions of years to develop into its current form.
    [by the way, did anyone see the Bill Nye vs. Ken Ham debate? I’ve seen it via youtube, if you ever wanted a scientist to explain how evolution works, and why the earth isn’t 6000 years old, just watch it, it’s worth the time!]

    Back to our problem/situation at hand, the hypothesis that this hidden rT3 pool exists in man has been stated by a team of scientists around LoPresti et al., not by me. I just dug out this >20 year old research paper that apparently no other scientist ever cared about.

    To adress carol’s question: No, to the currrent state of knowledge, there is no interconversion between T3 and rT3 possible in the human body. I find it very unlikely, since eliminating the T4 results in a (time-delayed, but existing) significant drop in rT3 concentrations in the bloodstream. If there were a conversion “T3 –> rT3”, then taking T3 only would most possibly not work, yet it can be observed that it does. Therefore, the most logical assumption is, that T4 indeed is the only source from which rT3 can be made, by means of deiodination.

    Jennifer, please understand that I am not a scientist, nor a doctor, although I have a Bachelor of Science degree in biology and chemistry. Therefore, everything posted here is my own personal theory / explanation model, except the scientific studys that I have posted as sources for my claims.
    I personally think it’s most likely that this “hidden pool” is either located in the thyroid gland or in the liver. The liver is like the “Amazon of the body” (meaning the online shop) where everything gets packed up, delivered, sorted, and (this is where the Amazon-model doesn’t work anymore) is being processed and transformed in a lot of different ways. Somehow, people often seem to think that the liver is just there for processing alcohol…that’s definitely wrong 😉 It can process, store, transform… a lot of things. Just as two examples, there are large stores of glycogene (an energy source for your body) and vitamine B12 existing in your liver, the B12 storage alone being about 2.000 to 5.000 mcg in size, while your body needs about 5 to 10 mcg per day. This B12 storage in the liver lasts for several years! I think it’s an educated guess to assume that a previously unknown large storage of rT3 may be located in the liver. The liver has one of the largest deiodination capabilities in the whole body, it would be the perfect place if you ask me.

    One last (important) thing, that I want to mention. Janie forgot to add it to her blog post. I have made a third assumption (assumption one and two are written in the blog post) regarding to *why* the body of patients with autoimmune thyroid diseases wants to create such large amounts of rT3, being much larger than anything observed on healthy persons while not ill, not cold, and well fed. Here it comes:

    Assumption No. 3:
    3. It might be possible that the body reacts to its own thyroid cells in the very same matter that it reacts to any foreign pathogen (e.g., a bacterium that would cause a typical cold). The very basic idea of an autoimmune disease is, that the body looses the ability to distinguish between its own cells and foreign pathogen cells. So, it is only reasonable to assume that the body reacts to its own thyroid cells in exactly the same way that it would react to any foreign pathogen: First, by attacking it via the specific immune system, and second, by massively increasing the rT3 production in the body, in order to shut the metabolism down for the duration of the illness, to save energy. It is known that healthy humans react in this manner when they have a typical bacterial infection.
    I clearly stress that this is only a yet unproven hypothesis, but it is a reasonable one. This hypothesis could explain the reason *why* the body of patients with autoimmune thyroid disease so desperately tries to generate these large amounts of rT3 that we can indeed observe via blood tests. It can also explain why patients, as to common observation, often feel hypothyroid long before their TSH rises above the upper normal range limit. (which, by the way, according to German researcher Völzke et al., should be set at approx. 2.1 mIU/L; see: http://www.ncbi.nlm.nih.gov/pubmed/15785248)

    Therefore, to close this long post, I personally think that eliminating this over-production of rT3 is critical in curing hypothyroidism. It seems that the body tries to “fight an infection” (meaning its own thyroid cells, which it doesn’t realize) and is therefore generating large amounts of rT3, just like it happens in healthy people as stated in medicine literature. And since it would take something in between a few years and a whole lifetime to totally destroy all thyroid cells, the “infection” is never cured, and the body gets stuck in what someone may laughingly call “flu mode”. The body is still generating large amouts of rT3 (to shut down the metabolism to save energy), and is still fighting the thyroid cells via the immune system, because it believes that the infection is still ongoing.

    If this is true, reducing rT3 concentrations to levels of healthy persons (about 200 pg/mL and below) first, and then reducing the rT3 production by strongly limiting T4 for the rest of the lifetime, may be the only known strategy that could fully cure hypothyroid symptoms. This does not mean that T4 has to be completely avoided though! The brain derives about 70-80% of its T3 via local deiodination of T4, because T3 cannot cross the brain-blood-barrier as good as T4 can. T4 also has a stabilizing effect on the well-being because of its relatively long half-time (8 days). Avoiding T4 completely may not be a good idea, there are even clues in research papers that T4 somehow has hormone effects in the body, that are completely different from T3; especially in matters related to hair (Source: van Beek et al., “Thyroid Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte Proliferation and Hair Pigmentation”, J Clin Endocrinol Metab 93: 4381– 4388, 2008).

    Therefore, I presume that after rT3 has been reduced to levels of healthy persons, one should add T4 again, but in small doses, large time-intervals (8 weeks or more), step-by-step, and of course new lab tests every time to ensure that rT3 doesn’t exceed above a level that a healthy person would have.

    Elenor, I totally agree with both of your points.

    I clearly want to encourage everyone here to do little experiments on their own, as long as you be careful while doing so.

    Reply
    • Tricia

      Sebastian, how do you reduce the rt3 concentration?

      Reply
    • Erin M.

      Thanks so much for all of the interesting information! Your assumption three definitely fits with speculations I’ve been entertaining about my own situation–Hashi’s with plenty of antibodies and plenty of symptoms, but normal TSH and fT4, but low fT3 and high rT3. It’s always good to put together more pieces of the puzzle! Now if you coul only explain where the adrenal piece fits into all of this… 😉

      Reply
      • Sebastian

        Low fT3 could be a result of too less iron, or too less selenium. Iron is needed for the thyreoperoxidase (TPO) in the thyroid gland to function properly, therefore an iron deficiency reduces the overall production of thyroid hormones. That’s the reason why iron deficiency causes symptoms that are very much alike hypothyreoidism, by the way.
        Selenium on the other hand is a vital trace element needed for the so called deiodinases to function properly. These are enzymes in your body that can convert T4 to T3, or T4 to rT3, or rT3 to 3,3′-T2, or T3 to 3,5-T2, or… you get the picture. Selenium is needed for the production of selenomethionine, an amino acid, which is then used in the active site of the different deiodinases.
        Both trace elements are worth checking out. Zinc and copper are also very important for the body in general. Iron, zinc and copper are the three most abundant trace elements in the body, almost everything would break down if you have deficiencies there.

        How the adrenal piece fits in my model?
        Well, that’s purely speculative of course, but I did think this one through and it’s simple. Unlike most other substances, the production of cortisol is mostely limited to a small part of the day, the early morning hours while you are still sleeping. That’s when most of the cortisol gets synthesized and released into the bloodstream by the adrenal glands. Now, on the one hand, my model states that the body is still hypothyroid while there is too much rT3 in the cells, inhibiting T3’s effect via competitive inhibition, while exerting almost no negative feedback on the pituitary TSH production (thus we can’t see this inhibition by just looking at the TSH lab test).
        On the other hand, my model predicts that the adrenal gland should be hypothyroid as long as there is too much rT3 in the cells that it is made up from. To be more exact, it will be hypothyroid as long as the ratio of free T3 and free reverse T3 in all of these cell’s cores will be lower than in a healthy individual, statistically spoken. Because the strength of T3’s effect can be increased by either lowering free rT3 concentrations, or alternatively by increasing free T3 concentrations. It is very important that this last sentence is fully understood; you can still overcome rT3’s inhibiting effect by pumping a lot more T3 into the cells.

        Now, for any other organ like the heart, that would not have a time component. The heart beats 24 hours a day.
        The adrenal gland, on the other hand, produces and secretes cortisol mostly in the early morning hours, in a very small time window.

        Therefore it’s not surprising for me that a large dosage of T3, taken at an exact time, is able to overcome the hypothyroidism of the adrenal gland temporarily, resulting in the organ to function properly in those crucial hours, and normalization of the cortisol morning peak. The timing of this dosage must be exact, so that the adrenal gland’s cells are flooded with T3 just as they need to start production of cortisol, and the dosage itself must be high enough to rise the intracellular free T3 concentrations to the necessary level.

        There is a method called T3CM, which interestingly does exactly the same thing. 😉 My model can explain why timing is so critical with this method: T3 decays rapidly in cells and bloodstream, one dosage only lasts for several hours, plus it needs time to be digested, build up in the bloodstream, and be transported inside the cells. After a few hours the T3 concentration in the adrenal gland’s cells will decay rapidly, therefore the inhibition through rT3 gets stronger, and the cells become hypothyroid again. And hypothyroid cells can’t produce enough cortisol.

        In my personal opinion, the adrenal gland producing too less cortisol (if not caused by Morbus Addison) is a side effect of a hypothyroid adrenal gland.

        Reply
        • Erin M

          Wow, thank you so much–sorry, I only checked in today to see your lengthy reply. I was mostly joking when I asked about where adrenal fatigue fits in, and then amazed to see your thought-through answer! I’ve actually started out with the T3-only and CT3M methods over the last few weeks, and am having good results so far. Thanks again!

          Reply
        • Orthomolecular therapist

          Hi Sebastian,

          My neighbour 🙂 (I’m from the Netherlands)
          Thank you for your insights.

          I am thinking the following:
          It seems like the hidden pool of rT3 is not bad.
          Just a emergency system of the body.

          So, if you have rT3/fT3 problems, what about the following:
          Improve the minerals/cortisol.

          This will increase the T4 and fT3.
          More T4 means the emergency rT3 will NOT have to be used and can remain dorment.
          More fT3 in the receptor is increased energy instead of rT3 in the receptor.
          More rT3 won’t be created since the problems (minerals/cortisol) have been.

          You said somewhere that with T3 medication the rT3 pool will still release the rT3.
          I can imagine that if you do not address the underlying issues.
          So with the above in mind, perhaps this can take place much faster?
          Perhaps even without medication? Not sure about the last one.

          I’m noticing pretty good resultst though with my idea described above in some patients.
          Hope you still read this. Would love to hear your feedback.
          Dankeschön 🙂

          Reply
    • Roger M. Wilcox

      Hi Sebastian. Is there a site, or a study, or even a passage in a textbook I could link to that describes the competitive inhibition and dynamic interplay between T3/rT3 and the T3 receptors? I’d love to have a citation I could use as a footnote in (say) a Wikipedia article on the subject.

      Reply
  6. Sebastian

    I’m using the “T3 only” method. So far, after 6 weeks, my rT3 is now twice as high as it was in the beginning. I’m continuing the method, but with an increased dosage to counteract the rT3’s effects. With my TSH being suppressed, and no T4 taken in, it’s only a matter of time before my rT3 will start falling.

    Reply
    • Janie Bowthorpe

      I’ve seen that happen repeatedly if someone isn’t on high enough of T3-only to suppress the TSH–i.e. the RT3 will continue to be made from your endogenous natural T4. By the way, many people can lower their RT3 just by being on small doses of NDT, too, or small NDT with T3.

      Reply
      • Sebastian

        I doubt that, since my free T4 has fallen from 1.3 ng/dL to 0.5 ng/dL, which is way below the normal range. While my free T4 has fallen rapidly, my reverse T3 has doubled.

        One could argue that the free T4 has fallen because it has been converted into rT3. But considering that I’ve taken no T4 at all for about 6 weeks, and have previously lowered my T4 dosage to 37.5 mcg even before I began with T3 only, I would be surprised if all of that reverse T3 would have been derived from deiodination of T4. Remember that rT3 has a very short half-time, the literature states about 4.5 hours.

        Therefore, cutting free T4 in half, and doubleing reverse T3, doesn’t make sense to me unless you assume a hidden storage of rT3.

        You’re right that it’ll be better to suppress TSH for the duration of the T3 only protocol, to further minimize T4 production via the thyroid gland. This is one reason why I greatly increased my dosage recently (30 mcg to now 80 mcg). The other reason is to hopefully counteract the competitive inhibition from the tons of rT3 circulating in my body now. This dosage will suppress my TSH for sure.
        (I tried the lower 30 mcg dosage for experimentative purposes, wanted to see if T3 only works without suppressing the TSH, since as you say NDT works too, despite it contains large amounts of T4)

        Reply
      • monsie pickles

        I have been on a high T3 up to 100 mcg/day and 1/4 NDT. After 5 months I had the most horrendous lab results. Scary.
        monsie pickles

        Reply
  7. Chrissie

    This is interesting but doesn’t explain my case… or am I just weird? I was on T4, and was supposedly well after nearly 3 years of treatment – according to my TSH results. But I felt terrible and was getting worse… I wanted to die. I persuaded my GP to prescribe T3 only and continued to get worse, but not as quickly. I managed to increase my dose a couple of times, but could not increase it again – every time I tried to increase my dose, I felt like I was going to die. It was terrible. I stayed in this terrible state for about 5 years before I got my hands on NDT – my last TSH result before switching to NDT was 59 – more than 15 times the maximum normal range and I was really ill, but I could not increase the dose. As soon as I started on the NDT, the TSH started to drop and I started to feel better. Unfortunately, I don’t have any RT3 or T3 measurements I can refer to as these were not taken at the time. Any ideas?

    Reply
    • Sebastian

      A TSH of 59 mIU/L was clearly hypothyroid (even dangerously high).

      Being unable to increase the T3 dosage could be through a lack of cortisol. This is the reason why every package of thyroid hormones contains a warning, that the person taking it should be checked for adrenal problems before starting to take the medication. At least that’s the case here in Germany (although patients and doctors just seem to ignore that).

      But to be honest, this is just soothsaying. It’s just a lucky guess. I’ve seen patients being unable to increase their dosages due to a lack of cortisol.

      Reply
  8. Olga L. Z.

    Can anyone tell me the relationship of the HCG diet and the changes in thyroid hormone dosing – In Dr Simeon’s HCG diet protocol (1950’s) it mentions that the thyroid may change to require less intake of hormone –
    Thakx

    Reply
  9. Giovanna

    Thx Sebastain, loved it and experimented on myself for 6 weeks no T4 (started by lowering first ten stopped it) however did not overly increase my T3 but From 37 to 50 max a day split in 3 times. i felt hypo and put weight on and my RT3 doubled!!!

    now i readded T4 (100 only) and on 37 T3 on most days and sometimes I up my T3 to 50. i am self medicating!

    Reply
  10. Giovanna

    forgot to add taht 10 years ago i had a RAI treatment so relying competely on T4 and recently, 6 months ago added cytomel T3.
    since i have lowered my T4 and started cytomel i felt better however i completely stopped T4 and relied on cytomel 50 I put weight on and exhibited symptoms of hypo. i am at my heaviest weight now and my RT3 doubled too that is why i decided to reintroduce T4

    Reply
  11. Jennifer Tiedeman

    Janie, could this be my problem? I currently have been on ndt for about 7 months. Every month it seems that I start getting a lot of anxiety and hyper symptoms. It seems that if I stop taking my ndt for a couple days I start to feel better. My morning cortisol was low but it is much better after using hc for 3 months. As far as I know, my iron is OK too. I’m feeling a little lost and hopeless that I’m never going to be optimal.

    Reply
  12. Rosemary Mossa

    Ok, I have different labs than a lot of you. I have been working on my high RT3 since November. It did go down to 13 from 27 in January. I had been on sutained release T3 and I asked my doctor to switch me to cytomel, he did (although it was the generic), I went downhill ever since started taking it. I was doing between 40 and 50 mcg.. My new labs are not good, my RT3 went back up to 25 and my TSH is 0.01, so very suppressed, my T4 went up to 1.5 (0.4-1.8)and T3 to 6.1 (2.3-4.5), so my T3 is to high and so is T4 and TSH way suppressed. What does all this mean, my doctor doesn’t know why my RT3 went back up when I am doing T3 only. Not sure what to do, he changed my prescription to brand name cytomel so am picking that up today. I know some people don’t do well on generic.

    Reply
  13. Irene

    Hi, I’ve just finished reading your amazing book and after struggling for years on Euthyrox, I am determined to find a doctor to prescribe NDT or at least synthetic T4+T3 drug, or check my cortisol and actually listen to what I feel. (fatigue, severe brain fog, inability to focus etc. we’ve all been there!) My question is do I need NDT if I have secondary hypothiroidism NOT Hashimoto’s? I’m 31 y old, female and I developed hypopituitarism around age 4 (diabetes insipidus and seondary hypo). Thank you!!

    I have great respect for everything you do and if anyone has thyroid issues, I’ll be sure to refer them to your book!

    Reply
    • Janie Bowthorpe

      Irene, yes, no matter what the cause, thyroid patients have found that Natural Desiccated Thyroid (or at the least, adding synthetic T3 to synthetic T4) gives them FAR better results! Thank you for your kind words! 🙂

      Reply
  14. cabro

    You theorize that the “hidden pool” is either in the thyroid or the liver. I have no thyroid, and I have rT3 showing and moving up and down. So, if you are right, that leaves the liver for this pool. Thanks for an interesting hypothesis and commentary.

    Reply
  15. ree

    don’t know anything but how I feel, so I continue on with very low doses of T3 everyother day like 5 mcg and still doing 50 mcg of T4, feel good and that is what I do

    Reply
  16. Linda

    I am confused on what the rT3/T3 ratio is supposed to be that is considered normal. Mine has gone from 4.9 to 14 to 9.1, and everyone is saying it should be 18-20. Is this like the TSH in that the lower it goes really means hyper? My T4 is always high at top range and my T3 is below optimal, although it has been in optimal range a couple of times. I was on 3.25 grains of Armour. Now my doctor cut my NDT in half for the T4 pooling but I feel so hypo I can’t function. I asked to have Cytomel added, but she refused. Seeing a new doctor tomorrow. Thanks for all the wonderful help you offer. You have enriched and changed so many lives!

    Reply
  17. Julia

    Sebastian or someone else – Do you know any scientific articles or studies of the mechanism how rt3 gets in the cell and clogs it? There is a huge controversy over the fact if rt3 actually takes t3’s place in the cell it among the patients and doctors in my country at the moment and I would like to back myself up with cold facts when fighting over this issue (just starting my t3 treatment). If I may ask you, is there anything you could possibly link proving that rt3 has hypometabolic properties? Thanks a lot forehand!

    Reply
  18. michele

    My TSH is very low and T3 is high, what do I do? my doc wants me to go back on levothyroxine?

    Reply
  19. Bob

    Sebastian if you’re still posting here I’m curious if your reverse t3 ever went down using the t3 protocol. I am doing the same thing and although I feel better physically on t3 some of my symptoms like my eyebrows thinning and my hair texture and loss have actually gotten worse and I’m wondering if it’s because my reverse t3 has gone up also I have a blood test scheduled for next Tuesday. I have been on t3 only for 4 weeks today

    Reply
  20. Bob

    Hi Janie,I understand rt3 comes from t4 but his rt3 going up and his theory got me thinking and researching. There are a lot of different theories about rt3, I even read one about too much t3 causing t3 to be converted into rt3. I do think his idea about t3 and rt3 going in and out and playing musical chairs has a lot of merit
    I am only on 20mcg of t3 at this time because I am self treating because i cant find a Dr that will do anything even though my rt3/t3 ratio is under 12 and am waiting on my next bloodtest before I go up anymore

    Reply
    • Janie Bowthorpe

      Hi Bob. T3 can’t be converted to RT3, though. And 20 mcg is definitely underdosing you, we’ve seen repeatedly. So if your thyroid still makes even some T4, it’s what can convert to RT3, especially in the presence of low iron and/or adrenal issues.

      Reply
      • Bob

        I don’t really think that t3 does but it was another idea that I read and his theory was to picture a cup and the excess t3 that flows over was turned into rt3, That was my point that there are all kind of ideas out there and no one really knows but Sebastians idea was the one that makes sense to me because I got a major energy boost right away from t3 even though I have a High RT3.
        I am going to increase my dose of t3 slower than I was , I got to feel a little hyper and dropped my dose from 40 back to 20 for a week. blood test on Tuesday, I am going to ask for feratin again and a saliva cortisol test along with the thyroid tests, all they did last time was blood cortisol and it was fine.
        I was hoping they would prescribe cytomel but I was told my I was within range and Rt3 means nothing by the endo, luckily my normal doctor will run blood tests to humor me

        Reply
  21. monsie pickles

    My myxoedema has increased to the point I can’t hardly walk. I am on T3 the top range (100mg). On the 14th January it will be 3 months I started taking T3 (not 100 mg straight away of course).
    monsie

    Reply
  22. Adam

    If RT3 increases as a signal to slow the metabolism down in times of bodily stress, maybe focus on reducing the stressors (inflammation, deficiencies, leaky gut etc) instead of tinkering with the hormone balances.

    Reply
  23. Lynette

    It would make testing rt3 so much easier if there was a stick and test like they do for sugar and iron. To have a tester that could read the amount of rt3 in your blood from a prick and a test strip would take away the cost and time of going to a doctor or a clinic. My doctor refuses to increase my t3. I ask for a rt3 blood test and she says she cant do it, I ask for a cortisol saliva test and she refers me to a endo which costs even more money which I have none of. I have given up on doctors in general sad to say.

    Reply
    • Lynette

      Also, is there a way to reduce rt3 without just waiting for the reserve to run out?

      Reply
  24. Eric

    Occam’s Razor tells us that all things being equal the simplest explanation is more often correct.

    The hidden pool idea requires that no one has ever found this pool. It also requires that either the pool is huge or RT3 in the pool has a very long half life beyond the 3-5 hours plus or minus usually believed. Otherwise it couldn’t last weeks to months.

    I propose a simpler theory.

    Enzymes can facilitate chemical reactions in both directions. The 5′ de-iodinase that is found in all tissue converts T4 to T3. I submit it could in cases of high T3 supplementation develop a bias in the other direction as well and create T4 out of supplemented T3. This newly created T4 could then be converted to RT3 by the enzyme 5 de-iodinase which is also available in all tissue except the pituitary.

    So you take more supplemental T3 than your body can handle and in some percentage of patients in two steps it converts it to T4 and then RT3 to get rid of it. Resulting in more RT3 than ever. And a rising blood test for RT3.

    The iodine necessary for the up-conversion of T3 to T4 is readily available in all tissue not the least because the enzymes cited above in all tissue are also stripping iodine from T3 and RT3 to create T2 and T1 after the active forms of thyroid hormone have done their job. The stripped iodine could be added to T3 when more than the body can handle is present.

    This theory also has the added benefit of explaining Wilson’s observation of patients experiencing what he calls compensation. Many of his patients feel better when initially going to some dose of sustained release T3 only to have a return of symptoms within a day to a week. It seems reasonable that the dose of T3 initially works until the tissue has time to react and begin up-converting that T3 to T4 and then RT3. Thereby reversing the surge in active T3 in tissue from supplementation. And reduction in the initial benefit.

    Reply
    • Eric

      While I am at it I will express my suspicions about another theory that is incorrectly being represented as fact. Many people are saying that RT3 blocking uptake of T3 at the receptor site is the cause of low thyroid symptoms. I have found no evidence that this has ever been proven. I believe that those who say or imply it blocks enough uptake to cause low thyroid are making an assumption that is a logical error.

      The great philosopher of science, Carl Popper pointed out that correlation is not causation.

      A high RT3 may often correlate with low stimulation of tissue by thyroid but may not have much direct cause in that low stimulation. It could be that high RT3 is a consequence of the same mechanism that causes too little T3 inside the cell. And, it is the low T3 inside the cell that results in under stimulation.

      There is a fundamental problem with the theory that RT3 blocks enough T3 uptake at the receptor to be a main cause of low thyroid. RT3 has a much, much shorter half life than T3. So it doesn’t hang around long enough to block much T3.

      Remember that the measurement of T3 in the blood is not necessarily representative of T3 in the cell for at least two reasons.

      Over 40% of the T3 necessary for optimal stimulation of receptors is created inside the cell after the thyroid hormone mix of molecules leaves the blood and enters the cell. Every cell in the body has the enzyme 5′ de-iodinase to accomplish this. If things aren’t going right inside the cell after the hormone molecules leave the blood this would not necessarily be directly picked up in blood tests.

      Cellular membrane resistance to T3 and/or T4 could also explain low intra-cellular T3.

      I have evidence of people with supposedly good F-T3/T-RT3 ratios above 20 who haven’t resolved symptoms.

      I have developed a simple formula using FT3, FT4 and Total RT3 as inputs which so far I have found to be more predictive in diagnosis and treatment than what I call the Holtorf ratio of F-T3/T-RT3. I call it the Holtorf ratio since Dr. Holtorf in California is the first one I heard using it.

      Reply

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