I'm looking to better understand (and help my Endo understand) the difference between what FT3 and Total T3 lab results indicate, and exactly why FT3 is widely considered the more relevant indicator to use in making adjustments to T3 dosing.
I understand the general concept of FT3 being indicative of the amount of T3 that is immediately available to cells, but my Endo (who I'm otherwise quite happy with) believes that T3 dosing should be adjusted based on Total T3 instead because "FT3 fluctuates and only tells you what's happening at the time the test was done, and is not a reliable indicator." I could be wrong, but I think this may be a common belief among Endos in the US. My doc is relatively open-minded, but I don't know enough to convince him to consider FT3 instead of, or at least alongside, TT3 in making dose adjustments. Right now my FT3 (which he does test at my request) remains steadily near the bottom of the range.
Any links to quality research or expert-written articles explaining why FT3 is more meaningful would be especially helpful.
Thanks so much in advance.
P.S. If it matters, thought I would add that in my case, my Total T3 has risen with starting and slightly increasing T3 dosing over the past year, but my FT3 has not.
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As you said, the FT3 tells you how much T3 is available for use by your body. The TT3 - or Total T3 - is exactly what it says. It's the total of both forms of T3 in the blood: Free and bound. But, it doesn't tell you how much of each.
The T3 you are taking in pill form is unbound - Free. And, you should test what you're taking, for one thing, quite apart from the fact that you need to know how much T3 your body has available.
T3 doesn't exactly fluctuate, but it is at its highest early morning, and the level drops thoughout the day - like TSH, only less so! And, they're quite happy to believe that the TSH tells them all they want to know, no matter what time it's tested.
"FT3 fluctuates and only tells you what's happening at the time the test was done, and is not a reliable indicator."
Well, you could say that about all thyroid testing. The TSH being the prime example. All blood tests are just snapshots. If he wants a more reliable indicator of status, he should do urine tests. But, I doubt he'd be able to interpret them. He's just parroting what he 'learnt' in med school, but I doubt he really understands why. If you asked him in-depth questions - especially about the fluctuation of T3 - I doubt he'd be able to answer.
"The T3 you are taking in pill form is unbound - Free. And, you should test what you're taking, for one thing, quite apart from the fact that you need to know how much T3 your body has available."
Thanks greygoose. Would you have any thoughts on why the addition of T3 to T4 in my case has increased my Total T3 but not my FT3? Is there some reason the body would prioritize attaching T3 to the proteins rather than leaving them as free molecules for the cells, even when FT3 levels are near bottom of the range and clearly more is needed by cells based on symptoms?
Most T3 is carried round the bloodstream attached to transport proteins i.e. is "bound". While this is the case it can't get into the body's cells and is biologically inactive.
To make T3 biologically active it must be separated from the transport proteins.
Free T3 tests measure the actual biologically active T3 (unbound T3).
Total T3 tests the total of the Free T3 plus the biologically inactive T3 attached to transport proteins.
There are people who have good levels of Total T3 and poor levels of Free T3, so presumably, for reasons I don't know, these people can't separate transport proteins from T3 very well.
The issue of not being able to separate transport proteins from the biologically active hormone happens with other hormones, for example, cortisol. A few people have posted that they have had good levels of cortisol in a blood test, but have very poor levels of free cortisol in saliva. Cortisol is always "free" in saliva as far asI know, but is a combo of free and bound cortisol in blood.
Iv been trying to explain this to my Dr, I take 75-100mcg but still get joint pain, fatigue and muscle weakness. Taking a higher dose doesn't get rid of the last 3 symptoms but considering how ill I was, I am probably as good as I will get.
So even on 150mcg a day I am no better than on 75mcg, so my free t3 is what I test. My t3 is over range for a few hours when it peaks but drops quickly.
Eek, sorry to hear that endomad, that's frustrating. So you don't experience symptom relief on the larger doses even though they raise your FT3, or do the higher doses not raise your FT3? I may be misunderstanding...
Seems I am stuck with the last 3 symptoms. There no point me taking twice as much to get the same level of recovery. I was under treated for many years and I just think the damage to my body was permanent. My thyroid was removed 2009 I went from super fit and strong to barely able to walk, 6 stone gained in 2 years, chronic pain, the list was endless, it was 5 years of absolute misery. So compared to that I am a lot better but back to who I was, no I still feel a million miles away from who I was.
i am so sorry endomad :/ glad to hear you're at last better but hope something new is discovered in the near future that is able to help people like you with TT get closer to who you were. i still have my thyroid but i feel like my anxiety (and, subsequently, rigidity) went way up when i went hypo, and within a few years i could tell that i had lost the laid back sense of humor that was once such a huge part of who i used to be. that coupled with increasing brain fog and bouts of severely low mood and increasing fatigue etc have changed me and my life trajectory significantly, so i feel you. i do have lots of hope for change though!
I had a great life up until then, so i miss who i was but at 60 years old now maybe it was time i slowed down a bit. Yes the anxiety is horrid, having always been really assertive ( pushy) that was and is still hard to deal with, i also have very low cortisol so no longer deal well with stress.
I lost a few friends when i was no longer the wild, crazy, spontaneous, fun person i was, they missed the old me, i told them to jog on as i wasnt there just to entertain them! but tbh i miss the old me. It was sad for my hubby to accept that actually i am much better but the girl he married 24 years ago has gone. It is life changing thats for sure. We do the best we can, i have a quieter life now in the countryside, dogs, gardening a few close friends but i am home at night ready for bed by 9-10pm or i am exhausted for the next few days. I have to plan my energy and use for only the things i really want to do.
The lack of decent drs, endos and general lack of understanding means we do not get the treatment we need soon enough. I was paid by nhs to tell my story to final year med students for 2 years at the local teaching university, in all that time i didnt meet a single dr who wanted to study endocrinology, they had virtually no training (half a day!) so i doubt things will ever get better.
Well I'm 60 now and I have no intention of slowing down ... it is the new 50 😉
I have felt very ill in the past but at the moment I am feeling very well so I am making the most of it because I don't know how long it will last this time.
You are right about not many doctors wanting to be Endocrinologists because I think it is very complicated and thyroid disease is so difficult to diagnose and treat. I went over 2 years going back to my GP who told me I was suffering from the menopause at 48. In a way I am lucky because I wasn't left as long as some people have been. At least I now know what to do if I become ill again because I don't trust any doctor with my thyroid health and never will.
:/ how long were you unwell before you started feeling better? that is a difficult story to hear and it shouldn't be that way.
under the NHS are patients assigned specific doctors that they must work with, or can you shop around for a different doctor if you're not happy with the one you have? from the stories i've read on here it sounds like the former? not that good doctors are easy to find in the US and of course individuals who don't have insurance or other resources are SOL (I was in this situation for a couple years until 2019, and it took me another 9 months afterwards of persistently researching and calling around before I finally found and was able to get an appointment with an endo willing to consider and treat my low T3). but in the US at least that's an option that exists, whether or not it is in reach!
My thyroid removed 2009 age 48 I went downhill fast by 2014 I was house bound with panic attacks, pain, anxiety, fatigue, I couldn't stay awake more than 1-2 hours, of course now I know I was slipping towards coma. Xmas 2014 I told my husband I didn't think I would be alive much longer. Fast forward a 2nd opinion with Dr peatfield adrenal support and NDT it was like switching the light back on, so I was very ill 5-6 years, what a waste of life, spent in bed, in pain and in tears.
My GP was an idiot, he did apologize but I hope he and everyone he ever cares about has their thyroid removed.
I went t3 only after a year of NDT, got a decent Endo but I still have crashes, joint pain and fatigue. I think the damage done during the first 5-6 years is permanent, most of my symptoms have gone but I never regained my full health. X
sorry for your experiences. i know many others on this board have had really devastating experiences too. so glad you’re doing relatively better and hope that continues
Thank you so much for the explanations greygoose and humanbean ! Those are very helpful. And I apologize for the delay - it's been a busier than expected couple days and unfortunately, the very limited bandwidth from my brain fog is what I struggle with most.
This may sound like a silly question but I'm just trying to understand this well so that I can have a productive discussion about this with my Endo tomorrow and be able to respond well to what he says: Does the level of Total T3 have any impact at all on what gets into cells? For instance, is it possible that if cells need more T3, bound T3 can be released as needed despite low levels in blood, so that if more is needed more is released from carrier proteins and quickly taken up by cells, keeping free-flowing T3 levels low? (I'm anticipating he may suggest something like this. )
I did a little research to try to understand why Endos in the US tend to look at Total T3 vs Free T3 and came across the same concept over and over: This is from UptoDate, a generally very well-respected resource among the medical community in the US - it attempts to summarize the latest well-accepted evidence-based research to help doctors with clinical decision-making (of course as we all know doctors don't seem to think about the fact that a lot of research doesn't ask the right questions or ask them in the right ways, but in any case...) - the last sentence in the excerpt is key here (despite being contradictory to the second paragraph):
"Serum free T4 and T3 — The free hormone hypothesis states that the unbound or free hormone is the fraction that is available for uptake into cells and interaction with nuclear receptors [17]. The bound hormone, on the other hand, represents a circulating storage pool that is not immediately available for uptake into cells.
Since drugs and illness can alter concentrations of binding proteins or interaction of the binding proteins with T4 or T3 (table 1), the free and total hormone concentrations may not be concordant. An example is estrogen-induced TBG excess, in which total T4 concentrations are high due to increased TBG-bound hormone, but the physiologically important free T4 concentrations are normal (see "Euthyroid hyperthyroxinemia and hypothyroxinemia"). It is therefore necessary to estimate free hormone concentrations.
●Assays – Most laboratories measure free T4 and free T3 by "direct" measurement.
- "Direct" free T4 – Direct free T4 measurements can be automated, and varying methodologies have been used by commercial laboratories [18]; however, none of these actually measure unbound T4 directly since free hormone represents only 0.03 percent of serum total T4. The perceived advantage of direct free T4 measurement is that confusion related to binding protein abnormalities is mitigated by providing values that allegedly take binding abnormalities into account. The disadvantage is that no currently available assay provides correct free T4 values for all the binding abnormalities that have been described. Direct free T4 measurements may be unreliable during pregnancy due to low albumin and other factors (see "Overview of thyroid disease and pregnancy") and in malnourished or critically ill patients due to low levels of binding proteins (see "Thyroid function in nonthyroidal illness"). The normal range also varies with the methodology used.
- "Direct" free T3 – Direct free T3 measurements use similar methodology and are increasingly available, but these assays demonstrate even higher variability than the free T4 assays, and we agree with American Thyroid Association guidelines that the use of total T3 measurements are more reliable [19]."
Do you have any thoughts on why, despite the fact that this article states that it is necessary to estimate Free T3, it still recommends testing Total T3? Is there a way to estimate Free T3 indirectly from Total T3? My endo will undoubtedly bring this up and I want to make sure I am equipped to respond (if what you've already explained above doesn't cover it).
Lastly, could you help me understand what the reasoning is that on this site it is suggested that T3 be tested first thing in the morning 8-12 hours after taking 1/3 -1/2 one's daily dose? I was hypothesizing that maybe this would capture one's lowest daily levels of T3 from dosing, balanced by relatively high levels of converted/naturally produced T3 per our circadian rhythms, equaling a sort of mid-level FT3 at the time of testing? I realize that may be way off, lol...
I'm afraid I can't answer your first question, about unbinding T3 to order. I don't think that has ever come up in anything I've read. So, perhaps that is just one of those things that no-one really knows - there are so many of those, where thyroid is concerned.
As to why American doctors prefer TT3 to T3, that also remains a mystery, as far as I'm concerned. But there is so much ignorance and misunderstanding about T3 in the medical world. Even though they always test the FT3 in Europe and the UK, doctors still believe the test to be unreliable. Yes, there is a test to guestimate FT3 from TT3 levels, can't remember what it's called. But why guess at it when you can just test it?
The reason we always say to get tested early morning, on here, is because the TSH is at its highest early morning. And, as all most doctors look at is the TSH, so we want it as high as we can get it! The reason for leaving 8-12 hours between the last dose of T3 and the blood draw - be it first, second or third dose - is a) to avoid the peak you get after taking it, and b) due to its short half-life, which is about 1 day, so you're testing it at its lowest point. But, doctors don't know anything about testing, so I wouldn't mention any of that, if I were you.
Ha thank you greygoose. I have no idea either why it would be better to estimate it from TT3 but that is what the article seems to be suggesting! However, if the guestimating requires a test, then my doctor is not utlizing that method either, as he doesn't do any other T3 tests besides TT3 and FT3, so I'm assuming he thinks testing TT3 on its own is sufficient.
He's actually quite a good doctor - certainly the best endo I've found in ten years - and hope I don't have to get him to completely agree with me on using Ft3 to guide my dosing, I think I just need to present a cogent argument to get him to at least try to do so (and ignore the already raised TT3) to see if it helps. I'll also try to get some clarity from him on his rationale for using TT3. If I can get him to at least acknowledge that TT3 MAY not provide an adequate assessment for the T3 levels my cells can utilize, that may be enough. I will have this thread open when speaking with him!
Thank you again, and by chance do you have any thoughts to my question above regarding why taking exogenous T3 would raise TT3 but not at all FT3?
However, if the guestimating requires a test, then my doctor is not utlizing that method either, as he doesn't do any other T3 tests besides TT3 and FT3, so I'm assuming he thinks testing TT3 on its own is sufficient.
'Test' wasn't the right word. I don't mean a test in that they draw blood, but the guestimation itself has a name that is put on a blood test report so that it looks like a test has been done. But, I'm a bit vague about all that because it's not something that is done outside the US. But, if all you get is a result called TT3, then he doesn't even bother with the guestimate!
do you have any thoughts to my question above regarding why taking exogenous T3 would raise TT3 but not at all FT3?
I'm afraid I don't, no. I didn't even know that that could happen, because - as I said - I've never had my TT3 tested. I've no idea how all that works.
Yes there are no other T3-related test results on on my blood report besides TT3 and FT3 (and the latter he has already told me he won't look at, and only orders each time at my request). So you're right that that he is not doing any sort of guestimating.
Hmm it's so odd that in the US Endos tend to look solely at TT3 and in the UK they don't look at TT3 at all, while at the same time in the US doctors will put individuals who are "sub-clinically" hypothyroid on exogenous hormone and in the UK they require TSH to go above 10. I guess the commonality is that neither country has it right!
Thank you for all of your input! Sincerely appreciated <3
Oh, most certainly neither has got it right! But, it's not just in the UK that they don't test TT3. I live in France and they don't test it here, either. Just FT3.
Regarding testing T3 at its lowest point, that certainly makes sense considering most doctors are hesitant if not outright resistant to dosing T3 at all, and the fact that we can always take less but not more than what is prescribed. In a perfect world it seems like getting all three (peak, mid, and low) levels tested would be most useful and telling - if nothing else in at least helping us all to better understand results of dosing and maybe why certain individuals like yourself prefer a single dose while others prefer dosing at intervals through the day. Maybe one day we'll get there.
I don't actually think that testing peak, mid and low levels would be helpful, at all. And, I absolutely know why I need to take all my 75 mcg in one go: Resistance to Thyroid Hormone. I need that massive hit to force just some of the T3 into the cells. If I divided it into three doses, it wouldn't have the same impact of flooding the receptors. Actually, it's got a lot better with time. I used to need to take 225 mcg all in one go! lol
WOW, quite a dose. wonder if everyone who prefers a single dose has some sort of resistance to thyroid hormone? i've seen resistance and flooding receptors mentioned on here before but being still somewhat new to T3, don't think i understand it - and since it's about 3 am here, and i can barely understand how to complete this sentence, will have to come back to it!
I don't know if all those that take their T3 in a single dose have RTH. Probably not. It's just that they're not affected by the peaks and troughs that some people find unpleasant. We're all very different.
It is complicated, and not enough research has been done into it all. And, even if they do the research, the results will take several lifetimes to filter down to GP level. Or even endo level, because they just don't do much reading on the subject after leaving med school. So, we're sort of stuck.
If I can get my brain working again I've considered going back to school and getting involved in endocrinology research myself to try to push research and policy for dealing with thyroid issues in the right direction. I know there are lots of folks trying to do this in one way or another already and there is a lot of bureacracy, but with social media etc. things are different than they used to be. Perhaps naive to think there will be a shift in my lifetime but I've been an activist one way or another much of my life and believe improvements are possible, even if only in small steps.
Thanks greygoose. Perhaps by the time I'm better I won't have any fight left in me and will want to think about all this as little as possible and focus on all the things I've had to put aside for the past many years , but we'll see!
The graphs come from the PDF link helvella gives in his post.
Obviously people are limited as to when blood samples can be taken - it isn't usually possible to get blood taken in the middle of the night.
So if your TSH was at its highest at 8am - 9am (during times when people normally get their blood samples done), then Free T3 would be at its highest at about 9.30am - 10.30am.
Lowest TSH would be at about 1pm - 2pm, and lowest T3 would be at about 2.30pm - 3.30pm. These timings are very rough based on the graphs - see the paper in helvella's post for the precise details.
I would also assume that people's sleeping times would affect peak production of hormones too.
Great news and wanted to let you know greygoose and humanbean ! My endo was sympathetic to the case I put forth regarding FT3, thanks to your input, and has agreed to raise my T3 dose to what I asked for. I also mentioned the amount of knowledge and help I've been able to gain from this board and that so many other folks who have similar issues have found relief by using FT3 to help guide their dosing.
In case you're curious, I asked him why he was so hesitant to use the FT3 test and he stated that not only is it a very limited snapshot, but also that the results are affected by so many factors, such as how long the lab waits to freeze the samples since enzymes in the blood that affect FT3 are still active, etc. Maybe the practices we use here in storing and transporting blood samples are less stringent than what is done in the UK and France. In any case, this time it worked out - we'll see what happens in the next appointment if my FT3 is still low!
Congratulations! I hope it all works out for you and you start to feel better. Just remember that, having been granted what you want (more T3), that you can add that T3 at any speed you want, you don't have to add it at the speed your endo suggests.
Some endos prescribe, say, 25mcg T3 and then tell patients to take it at some particular time of day, and they just seem to be setting the patient up to fail. But you can cut that 25mcg tablet into any number of doses that you want to, take it when you want and increase your dose at the speed you feel comfortable with.
Also, in the UK at least, information on adverse effects of prescribed medicines has been collated since 1967. There hasn't been a single death from taking T3 in all that time. The number of patients who are terrified of thyroid hormones thanks to scaremongering by doctors is absolutely shocking.
Thank you humanbean, and for the suggestions! I actually asked for a very conservative increase of only 20%, and having struggled with increasing T3 in the past (granted, I later learned my issue then was low iron), I started with only a 10% increase the first ten days (I had actually already started this before my endo agreed to raise the dose ). I also raised my T4 dose 10% (FT4 was .94 , range .82 - 1.77 and FT3 was 2.4, range 2.0 - 4.4). I'm actually more scared of being overmedicated than undermedicated because for 8 years on T4 therapy alone, with FT4 levels always mid to high in range, I had terrible, terrible insomnia. As I lowered my T4 dose to accommodate T3, although I've felt much worse in many ways being more hypo this past year, I've actually been able to sleep. I can't say I feel better rested yet, maybe because my levels are still much too low, but it has been such a relief to be able to generally sleep through the night and I never want to go back to living like that again. I'd almost rather be too tired to get out of bed all day than to struggle with sleep every night.
Oddly, I felt quite a bit better almost right away on the 10% increase than I have for the past few days on the full 20% increase. My mood and energy were strangely better on the 10% increase, and I didn't feel like I was "crashing" in the evenings. I'm hoping the full dose is just taking some time to stabilize - or do you think I should have stayed at the 10% increase longer? My B12, folate, and Vitamin D were optimal and Ferritin was ok (65, range 15 - 150 - and I've increased my supplementation a bit) so I don't think it's nutrients that are causing an issue. It could be the split (he advised me to take 66% of my dose in the morning and 33% several hours later, whereas I was doing a more even split before), so if this doesn't settle out in another week I'm thinking I'll try changing the split more evenly. I'm also planning on gradually changing the timing over the next several days so I'm taking doses 4 am and 9 am vs 8 am and 1 pm. Or maybe even trying to take all at once like some do. It's annoying that it's so difficult to figure out proper dosing!
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