T3 Controversies: Should T3 Levels Be Normal When Treating Hypothyroidism?

Evidence-Based: Written by a Board-Certified Endocrinologist

In Comments and Controversies on Hormones Demystified, I laid out the case for why I needed to write this series of posts about T3. In this and other articles on the topic, I address the myriad claims and questions that have come up over the years in the Comments section of T3 Or Not T3 – Exploring The Controversy. Per my current Comment policy, I will aggressively moderate reader-generated content that doesn’t meet the standard. I would also ask you to restrict your thoughts, questions, and theories about T3 to the narrow subject of each post in the T3 Controversies Series. I believe this will make the reader experience better for everyone, allowing people to more easily find the information they need. Let’s get started on today’s subject!

Claim: Because T3 is the active form of thyroid hormone, it is important to monitor T3 levels on thyroid hormone replacement therapy1 and ensure that T3 is within the normal range.

HD: Mostly False. Although T3 is the active form of thyroid hormone, I must grade this claim as “mostly false,” because targeting T3 levels to a specific number or range does not have adequate data to support it being presented as a necessary strategy. Let me get a couple of disclaimers out of the way, before we dive into the meat of this post:

  • T3 levels might be an important target for a subset of people with hypothyroidism, but studies have failed to demonstrate how to identify these people.
  • Saying that T3 levels are generally unhelpful in the management of hypothyroidism ≠ saying that T3 (liothyronine) is never needed as an add-on to T4 (levothyroxine) therapy.

As regular readers know, this is not a medicopedia website, so I don’t plan to simply duplicate information you can find at reputable thyroidology sites, like American Thyroid Association or Thyroid Disease Manager. Rather, I will attempt to synthesize and distill the information from various sources, adding my opinion regarding how to interpret and apply the data in real life.

Starting With First Principles

Let’s start with going back to first principles, as I haven’t seen this T3 topic addressed in quite this way in the literature. When I think about measuring or monitoring free T3 levels (FT3), the very first thing that comes to mind is: the typical hypothyroid person has never checked a FT3 prior to becoming hypothyroid. That’s unfortunate, if one desires to restore FT3 to its normal baseline2.

The next logical question is: if we knew someone’s baseline FT3, would that be helpful? The answer to that might seem like an obvious “yes,” but it’s not that simple. In order to claim there is utility in knowing the baseline FT3, we would have to make several assumptions:

  • FT3 levels in the blood clearly correlate with symptoms.
  • FT3 drops in a progressive, linear fashion as thyroid failure progresses.
  • FT3 measurements are reliable, reproducible, and don’t change much throughout the day in euthyroid3 people.
  • FT3 is always somewhere within the normal range in euthyroid people.
  • FT3 levels in the blood correlate well with FT3 levels/activity in individual tissues.

Now, let’s examine each assumption and see how it holds up:

Assumption: FT3 levels in the blood clearly correlate with symptoms.

HD: False. There is a fair amount of literature looking at this issue, and you’re more than welcome to peruse it at your leisure, but I hope to save you the time4. In the vast majority of hypothyroid people on levothyroxine who feel well, FT3 will be low-normal or slightly low, FT4 will be normal or slightly high, and TSH will be normal. Unfortunately, hypothyroid folks on levothyroxine who don’t feel well often have the same thyroid function test profile. Basically, these two cohorts look the same on paper, meaning that we cannot use T3 levels to guide clinical decision-making.

Assumption: FT3 drops in a progressive, linear fashion as thyroid failure progresses.

HD: False. As the active form of thyroid hormone that gets inside cells, binds to nuclear receptors, and gets the job done, T3 is super-important. The body realizes this and is therefore remarkably adept at defending T3 levels. What does this mean? It means that, if your thyroid is failing or if some scalpel-wielding surgeon removes it, the body will try its best to maintain blood T3 levels at their usual set point. As a result, T3 levels often don’t drop that much until the thyroid is severely damaged and/or the body has maxed out its compensatory mechanisms5.

Because of all this, checking T3 levels in the setting of untreated hypothyroidism will often yield low-normal levels. Unfortunately, you won’t know if the FT3 used to live higher in the range and is barely hanging on for dear life; or if the FT3 has always been perfectly happy to reside in its current portion of the range.

Assumption: FT3 measurements are reliable, reproducible, and don’t change much throughout the day in euthyroid people.

HD: Mostly False. Without getting bogged down in an overly detailed description of laboratory methodology, the typical FT3 assay can be thrown off by lots of things, and it tends to be less reliable toward the lower end of the reference range. While FT3 levels are fairly stable over the course of days, weeks, and months, T3 production does have a subtle circadian rhythm that could result in slightly different values at different times of day.

Assumption: FT3 is always somewhere within the normal range in euthyroid people.

HD: False. In order to assign importance to T3 levels, we have to assume that people with normal thyroid function always have normal T3 levels. Unfortunately, that isn’t necessarily the case. In part, this is due to assay issues, particularly when the FT3 likes to live near the lower end of the normal range. In that case, it may register as slightly low, even though that person is “normal.”

There are also other situations in which people with normal thyroid function will exhibit low FT3. For example, people eating a ketogenic diet or engaged in significant fasting may have low FT3, even though they feel fine. People who land in the hospital with a severe non-thyroidal illness will also often have low T3 levels, making it very difficult to assess thyroid function using that test under those circumstances.

Assumption: FT3 levels in the blood correlate well with FT3 levels/activity in individual tissues.

HD: False. I’ve written about this ad nauseam throughout this blog, but it bears repeating. Most tissues in the body can regulate their T3 levels and/or activity through a number of physiologic mechanisms. The T3 level in the blood cannot tell you what the body’s tissues are doing at the local level. In fact, this is probably why FT3 levels in the blood can be low in people who feel just fine – they are likely up-regulating T3 conversion, transport, and action at the tissue-specific level.

When Might a FT3 be Helpful?

I think an argument could be made for checking a FT3 in someone on levothyroxine +/- liothyronine who feels poorly despite normal TSH and normal-slightly elevated FT4, and who has a pre-hypothyroid FT3 level for comparison. Admittedly, this will apply to an extremely narrow segment of the hypothyroid population, but I’m offering an evidence-based recommendation here, and the evidence is what it is6.

In a person such as this, we could titrate the levothyroxine or liothyronine up to restore a low FT3 to its pre-hypothyroid, presumably normal level. If symptoms improve, then we’d have our answer. Likewise, if symptoms fail to improve, we’d have our answer – it’s not the thyroid.

The biggest problem I see with the above strategy, however, comes into play when using liothyronine as an adjunct to levothyroxine. Because liothyronine’s half-life is fairly short, and there is no sustained-release version7, it’s hard to know when to check the FT3 in relation to the dose. The best I can say is: if one takes three equivalent doses of T3 roughly every 8 hours, that would somewhat mitigate the delta between the peaks and troughs of FT3. That said, I’d probably check the FT3 4-8 hours post-dose, given that the peak is usually seen at 2-4 hours post-dose. In other words, I’d rather see what the level is doing between the mid-point and the trough, to make sure that there is sustained exposure to whatever FT3 level I’m targeting.

Of course, the aforementioned strategy is mostly academic, as most people are not going to take a medication thrice daily. The highly motivated readers of this blog might, but trust me – most people I treat with liothyronine can’t remember to take the second dose of the day, let alone a third. Suffice it to say, I am very much anticipating the eventual release of a true, sustained-release T3 product. Not only would this have the potential to relieve symptoms in those who can benefit from T3, but it will make it easier to study the biochemical monitoring of T3 therapy.

But I Read My FT3 Should be High-Normal

I am going to close out this post by addressing one of the most misguided pieces of advice promulgated across the quack-o-sphere. The recommendation on many websites to push levothyroxine, liothyronine, or pig thyroid doses up in order to achieve high-normal FT3 levels seems to be widely justified by some version of the following: “In our experience, this is where people feel best.”

Sorry, but I’m calling BS. First, if this strategy was the holy grail of treating hypothyroidism, there wouldn’t be tens of thousands of dissatisfied hypothyroid people frequenting thyroid forums. They’d all be “adequately” treated by now – either by alternative medicine providers willing to prescribe heroic doses of thyroid hormone or by Dr. Dark Web, where desiccated thyroid can be purchased without a prescription.

Second, pushing T3 levels to high-normal assumes that more thyroid hormone is always better. This is flat-out wrong and potentially dangerous. Most thyroid bloggers and alt med enthusiasts lament rampant under-treatment of hypothyroidism. They often make unsupported assertions like, “Before the TSH blood test came along in the 1970s, people were on 2-3x as much levothyroxine and nobody was dying from arrhythmias or getting osteoporosis.”

Piggybacking on my second point, my third point is that these MaxT38 enthusiasts completely ignore the fact that most people have no knowledge of their pre-hypothyroid, baseline FT3. Remember that the reference range for most blood tests will show a bell-curve distribution, with the smallest numbers of people at either end of the range. Therefore, does it make any intuitive sense to recommend that all people push their T3 levels as high as possible? Does it not stand to reason that the vast majority of these MaxT3-ers will bathe their tissues in excessive amounts of thyroid hormone9?

Fourth and finally, I can tell you that I see a fair number of people who have been inappropriately prescribed large doses of thyroid hormone to achieve “optimal” T3 levels. They come to see me because they want a second opinion. Why do they want a second opinion? Because they are fatigued, sleeping poorly, losing hair, anxious, achey, and depressed. Sounds very much the same as under-treatment, doesn’t it?

By reading this site and interacting with me and others in the Comments, you agree to abide by my Disclaimer. As a reminder, please restrict your comments and questions to the narrow topic at hand. There are plenty of opportunities to discuss different claims and controversies in my other T3 Controversies posts.

Image Credit: Photo by Chris Barbalis on Unsplash

  1. For the purposes of this discussion, thyroid hormone replacement therapy will be defined as levothyroxine therapy, which is the standard of care. I will touch on liothyronine (T3) add-on therapy, but I will not be discussing desiccated thyroid hormone therapy in this post. []
  2. Don’t you dare cut and paste this statement into some thyroid forum and claim that HD says everyone should check a FT3 at some point in their life to get a baseline. You would be taking my statement out of context, and you know it. []
  3. This term refers to normal thyroid function. []
  4. If you want a list of source papers, check out the bibliography of this document. []
  5. i.e. increasing T4:T3 conversion, decreasing T3 inactivation, increasing T3 transport into cells, increasing T3 binding to nuclear receptors, etc. []
  6. I suppose that we could start routinely checking FT3 in our patients about to undergo thyroidectomy, in order to provide this data point for more people. []
  7. Please don’t tell me about your “compounded” sustained-release T3. Compounding pharmacies do not have to prove that their product does what they say it does. The pharmaceutical industry has been working on this problem for decades and still hasn’t launched a product. []
  8. I think I just coined this term, but please let me know if I’m mistaken. []
  9. The body will obviously attempt to compensate by down-regulating T4:T3 conversion, decreasing T3 transport into cells, and decreasing T3 binding to receptors. But it is quite possible that high levels of T3 in the blood will overwhelm the body’s compensatory mechanisms, exposing the tissues to too much T3. []

23 Replies to “T3 Controversies: Should T3 Levels Be Normal When Treating Hypothyroidism?”

  1. Thanks for the post. Anxiety about whether the doctor should be ordering T3 tests or a “full thyroid panel” is something I see very often online.

    But I’m not sure I understood what you meant to say near the end, about the patients who come asking for a second opinion. Are the symptoms of overtreatment similar to the symptoms of undertreatment, or is there something else going on?

  2. YES YES YES. omg, this site so good, so logical. As someone struggling to find “normal” after a hemi_T_ectomy, it is the absolute truth that “body will try its best to maintain blood T3 levels at their usual set point.” Over two years, my T3 is the same on 50mcg levo, 25mcg levo, 1 1/2 grains NDT and also, on…wait for it….NO MEDS. Your body is amazing at making all the T3 it needs, I can def. attest to that. I am someone who once falsely believed the MaxT3’ers and that maxing out T3 is…”where people feel best” and tried it with a #fail. Months of AFIB, extreme anxiety even weight gain resulted even as my naturopath kept telling me though “but your blood tests look great “… “pushing T3 levels to high-normal assumes that more thyroid hormone is always better. This is flat-out wrong and potentially dangerous. ” AMEN. #proofinthepudding and thanks for posting all your wisdom.

  3. I think this is one of the better posts you have made because it’s about a commonly stated functional medicine claim (mid-upper FT3 levels and mid-upper FT4 levels). I personally still like to get all three tests done just in case sometime in the future they become useful. I personally do not know if the tests are useful or not. But I do find them interesting when I see the results. So far, I can see no obvious patterns for these tests based on past results. Do endos talk about these items in their get togethers? It would be useful for them to have answers when questioned by patients. When I asked an early endo about FT3 levels, he said “why would we test for that?”. It made me think he didn’t know what he was doing. However, maybe a better response would be “I know you read about FT3 online, but here is why it’s not needed”

    1. I hear you, Mike. I agree that it would be better to use your suggested verbiage. That may have been your early Endo’s way of prodding you to tell him what you read, and then perhaps he would have addressed your concerns based on whatever you said next. As a group, Endos tend to focus on issues that have new information or are very controversial within the field. Since following T3 levels in hypothyroidism is not controversial within mainstream Endocrinology, it is not a major focus of our CME lectures. The only controversy is that which has been manufactured by alt med.

  4. “First, if this strategy was the holy grail of treating hypothyroidism, there wouldn’t be tens of thousands of dissatisfied hypothyroid people frequenting thyroid forums.”

    Wait what? You have it backwards. If mainstream thyroid treatment was the holy grail of treating hypothyroidism, people wouldn’t be flocking to thyroid forums trying to figure out how to feel better. If PCPs and endocrinologists were doing a great job, people wouldn’t be frequently complaining of fatigue etc despite following their doctor’s orders and having good TSH values. Standard thyroid treatment as it stands seems to be missing something and no one seems to be able to figure out what that is.

    1. I would have to agree with Aims on this one. I think we as thyroid patients have been failed by both mainstream and functional medicine. It’s not a small amount of thyroid patients having issues. It’s a large percentage. And T3 is one of the potential reasons. I think it’s a much more complicated issue than is thought about in mainstream medicine. And possibly Hashimotos itself is one of the reasons.

      1. I think that Aims, Mike, and I can agree that there are a large number of people who feel unwell and look to thyroid forums for answers. However, I must push back on several of your points/assumptions:

        – While this may represent a sizable number of people, it is still a small percentage of the overall number of hypothyroid folks out there. Most hypothyroid people are doing just fine on standard therapy.

        – It is highly likely that a sizable percentage of the people on thyroid forums looking for answers do not have a thyroid problem at all. They either hope to have an easily treatable thyroid problem to explain their myriad symptoms, or they have been misdiagnosed with hypothyroidism by alt med (or even a mainstream healthcare practitioner).

        – Of the truly hypothyroid people on thyroid forums, it is highly likely that a sizable percentage of those who feel unwell have other, unaddressed problems to account for their symptoms (poor sleep, diet, exercise, mental health, stress management, sleep apnea, etc).

        My point is that, if MaxT3 was the answer to most of these people’s problems, the number of people on these forums would dwindle down to next to nothing. That has not happened.

        1. That’s reasonable. I think you may need to add a few things to the list. Some of which are common among people with Hashimotos: Gut infections, nutrient deficiencies, SIBO to name a few. I had to ask my doctors to test for Vitamin D and Iron. Both of which can be commonly an issue. Both of which were either at the lower end of normal or below range. I feel the Hashimotos side of things are often ignored. But yes, T3 for the sake of T3 is not always the answer. However, it could be exactly the answer for people who are not quite right on T4 only treatment. And I have seen a lot of folks claim that is what greatly helped them turn a corner. So it’s certainly a thing for people who are struggling. But I feel that the dosing of combination medicine is not well understood enough by Endos and I’m afraid to try it under the care of my Endo.

          1. I think an Endo who is open to the concept of add-on T3 therapy will likely be able to manage that appropriately.

  5. Does it stand to reason that when LT4 is increased the body just clears out the excess it doesn’t need (via rT3)? If that is the case pushing LT4 up and taking LT3 to “correct” rT3 and increase T3 seems like a waste of time.

    1. I would not recommend thinking about this issue in the context of rT3. When T3 medication is used, it is used with the intent to improve symptoms, not with the intent to “correct” rT3.

      Nonetheless, I think I understand what you mean: T4 will be inactivated – to some extent – to rT3, when the body determines it needs to do that. But I think it’s too reductionist to say that taking T3 to raise T3 is a waste of time for that particular reason.

  6. One underlying issue that may be confused with fatigue symptoms is endocrine myopathy. As I understand it, it’s caused by excessive or incorrect amounts of thyroid hormone damaging muscle tissue. Apparently it takes months to get relief after thyroid levels are restored. I wonder if people taking max doses of thyroid hormone could make this worse? Great article, much appreciated.

    1. We tend to see these muscle symptoms in people with untreated (or undertreated) hyperthyroidism, who have had high thyroid hormone levels for awhile. But yes, if someone takes too much exogenous T3 or T4 (or both) for long enough, it could happen.

  7. “There is a fair amount of literature looking at this issue, and you’re more than welcome to peruse it at your leisure, but I hope to save you the time”

    HD, I have read through the guidelines referenced quite a few times (quite the read). But I found they are fairly inconclusive on the use of T3 with T4. I also don’t believe there is much research in this area. Partially because in general doctors do not test FT3 on a regular basis. If you look at the guidelines 13B and 13C where they discuss combination therapy, the first one is weak recommendation moderate quality evidence and the second is insufficient evidence. Also, a lot of what I got from the entire set of guidelines is more research is needed (especially in the area of combination therapy). Again, I’ve seen more than a few people say adding T3 was a game changer for them. It doesn’t work for everyone, but it certainly needs consideration. I’m still personally going to give T4 only a full try (getting my TSH between 1-2) before I got that route. But it seems to me that there clearly needs to be more research on this. Especially based on patient experiences (many of which went to someone other than an endocrinologist to get help). Let’s not forget the entire reason those guidelines were created is because so many hypothyroidism patients don’t do well on T4 only treatment.

    1. I agree with pretty much everything you said, except that there are a bunch of studies out there about this subject. It’s just that the studies – when taken as a group – are inconclusive. I totally agree that we need more research on when to use combination therapy and the optimal way to manage it.

  8. Do you think the studies are inconclusive due to study design, medication doseage/administration, and/or some other factor?

    1. Good question. What I meant is that, taken as a whole, the studies do not conclusively answer the most important questions we have: is combination therapy better, what’s the ideal regimen of T4/T3, when are T3 levels truly helpful, etc. The inconclusiveness is due to conflicting results among studies, different study designs, lack of a physiologic delivery method for T3 medication, etc.

  9. I am curious what effects lifelong exposure to strontium 90 might have on the pituitary/hypothalamus and thus on thyroid function. This situation resulting from exposure to fallout from the above ground testing of the 1950’s and resulting absorption of calcium seeking strontium 90 into the bones—skull in particular—of infants seems to be a topic that could have impact on why some of us old farts have some things going on that are masked by TSH levels being “in range”, regardless of us feeling like garbage and having hypothyroid symptoms. Is this addressed in med. schools as part of our national history that does have health implications? If I understand the radioactive strontium 90 has a half-life of 20 or so years, meaning it is exposing brain to radioactivity for most of our lives, and the reaches of exposure went far beyond the states in and adjacent to the testing sites due to drift (hence the term downwinders). My fT4 and tT4 levels are always low/low normal, TSH normal to low normal, and fT3 in lower quarter of range. Shouldn’t TSH be high in that situation?

    1. This is veering off topic, and I don’t recall encountering anything written about strontium and the pituitary, so I’m going to pass on commenting about it. As for the answer to your question about low-nl T4/T3 levels and low-nl TSH, that is often perfectly normal for lots of people whose bodies prefer living in that portion of the range. Could it represent central hypothyroidism, though? Well, that’s a fairly rare condition, and it is typically diagnosed when FT4 is frankly low, so I’d have to be really suspicious of central hypothyroidism to start going down that road. In other words, there would have to be signs of other pituitary hormone problems, or the person would have to be at high risk for hypopituitarism (like from a tumor or TBI, for example) for me to consider going down that road.

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