✅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.
- 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.
- 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.
- This term refers to normal thyroid function.
- If you want a list of source papers, check out the bibliography of this document.
- i.e. increasing T4:T3 conversion, decreasing T3 inactivation, increasing T3 transport into cells, increasing T3 binding to nuclear receptors, etc.
- 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.
- 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.
- I think I just coined this term, but please let me know if I’m mistaken.
- 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.