A few years ago, I wrote a blog post explaining why T3 (Liothyronine) is best taken in multiple doses during the day. This blog post is a follow up to that one, based on a series of questions and answers that happened recently between a thyroid patient and myself. You may find it interesting.
Q1: Just something I’m curious to know. I’ve read that the half-life of T3 is between 6-8 hours. How does it maintain an optimal body temperature over 24 hours if that half-life is correct? Thank you.
A1:
The blood half-life is about 24 hours. However, most people feel that a T3 dose only seems to last 4-8 hours. The blood half-life is largely irrelevant apart from lab testing considerations.
When someone takes a reasonable sized T3 dose, for example 10 – 25 mcg of T3, the FT3 peaks in the blood during the first couple of hours of swallowing it. The T3 begins to enter the cells and connects with the thyroid receptors in the cell nuclei. This begins to increase the rate of gene transcription within the chromosomes of the cell nucleus. As more T3 arrives from the dose, the rate of gene transcription increases. This makes the cell function properly and produce the proteins that it is supposed to. Even when the blood FT3 levels eventually begin to fall after 6-10 hours the effect on the cell nuclei continues.
One dose of T3 per day, taken at the size it would need to be to facilitate enough T3 to keep the cells working for 24 hours, is usually far too large for most people to deal with and some people have a much faster clearance of T3 which also makes it difficult to cope with one dose.
However, 2-4 doses over the day usually is enough to ensure that more T3 begins to rise in the blood again before the cell nuclei have lowered the rate of gene transcription – thus allowing the cells to chug along at a nice rate, even though the blood levels might fluctuate.
So, this is all about what happens in the cells and nothing at all about the blood levels. None of the interesting stuff can, of course, be measured directly unless we dissected you – which I think would be somewhat unpalatable! All we can do is measure the effect of the T3 – hence signs and symptoms are our best assessment of how the cell nuclei are getting along. See my books for more about using signs and symptoms and managing T3 dosing (and the dosing of the various thyroid medications).
This is also why multi-dosing of T3 works so well and can work far better than slow release T3 when someone is using a good amount of T3 or T3-Mostly or T3-Only.
But basically, we can do really well over 24 hours once the cell nuclei have got their momentum up with the T3 doses and have the right rate of gene transcription in process. Yes, it can go a little slower during the night while we sleep but that’s fine as we aren’t as active. Some need more T3 in the night to allow the pituitary to function well enough to make cortisol (hence the Circadian T3 Method – see my books for more on CT3M).
I hope that explains it.
Q2: It’s very nice to have this explanation. What I don’t understand is, what is the blood FT3 doing?
A2:
The blood FT3 is doing absolutely nothing. T3 does nothing until it is transported to the cells. Most of its work happens at the cell nuclei and also at the mitochondria. When someone has no T4, the T3 can also operate at the cell wall thyroid receptors. But in the blood – nothing at all. The T3 just circulates so that it can reach the cells of the tissues and organs throughout the body.
This is the problem with doing blood testing. Blood testing is a kind of surrogate measure of what might be happening at the cell nuclei. But we don’t know how effective the transport into the cell nuclei through the cell wall is. We don’t know how easily the T3 can reach the nuclear thyroid receptors.
But doctors think they can measure FT3, FT4 and say we are ok – just based on a poor surrogate measure. Even though our signs and symptoms might suggest we are very hypothyroid still. Some doctors even think that TSH is even a surrogate measure for FT4 and FT3 and rT3 – which is even more silly. Some don’t even measure the active hormone FT3. The entire current paradigm of endocrinology practice is really flawed.
This is why my books focus on the use of signs and symptoms, with blood tests giving only an indication that dosage changes are moving things in the right direction. Even aiming for specific blood test targets of FT3 in the range or rT3 in the range is nuts. We don’t know what this is translating to in terms of cellular effectiveness of T3 for an individual.
Some thyroid patients seem to put so much trust in their blood test results and think searching for some magic numbers for FT4 and FT3 is what they need to do. But these results vary from time to time and they really are only shadows of what the real picture is within the cells and the cell nuclei.
Q3: Thank you for this extended explanation. When someone is on quite a lot of T3 they often have to avoid taking the medication for many hours prior to any FT3 test, just to avoid the FT3 result being over range and scaring the doctor, thus having their T3 dosage reduced. A question I have always had is , why would we need our FT3 to be this high at all?
A3: The blood levels don’t matter, especially when measured too close to a T3 dose. The FT3 doesn’t do anything in the blood. If your signs and symptoms are fine then you’re pretty much in good shape. FT3 fluctuates far too much after a T3 dose is taken and it can get very high for several hours before it eventually falls again. The lab ranges are designed for healthy people and those on T4 medication, so they are not really suitable for those on mostly T3 treatment when FT3 levels fluctuate violently in the blood after T3 doses. See: https://paulrobinsonthyroid.com/can-ft3-be-used-to-manage-liothyronine-t3-thyroid-treatment/
Q4: So, it’s okay if we walk around every day with an FT3 level ABOVE range (if we feel good)? The only reason we disguise that is for the purpose of keeping the doctor happy?
A4:
Yes this is true for some people, especially if they are taking a lot of T3 medication. If their signs and symptoms show no evidence of being hyperthyroid at all, then testing FT3 within hours of taking a T3 dose and finding it high is not a concern. If I tested my FT3 within 12 hours of a T3 dose, it would be around 9-10 and my local reference range is 3.4-6.7. So, I tend to leave 18-24 hours and test trough levels – by which time my FT3 is in range. Some thyroid patients may need to leave longer to get both FT3 and TSH in range. It is best to test this privately first – to avoid nasty surprises and having your much needed medication level reduced.
But you need to be certain your signs and symptoms are good and not suggesting that you are on too much thyroid medication. These include blood pressure, heart rate and body temperature. Checking blood calcium is also good as too much T3 can raise it. An ECG (EKG) is a good idea too during the period of titrating your T3 dose and maybe occasionally thereafter.
These comments would be heretical on many thyroid groups by the way. Even many of the patient groups have been conned into thinking they have to adhere to thyroid lab tests and ranges that are designed for healthy people or those on T4 based thyroid medication. The people in these patient groups often talk about being in the upper quartile for FT3 or lower half for rT3, but they are still playing the lab test game that the endocrinologists and doctors have told us we need to abide by – even if this keeps many thyroid patients in a permanent symptomatic state of hypothyroidism.
Q5: Last question. We’ve discussed FT3 a lot, what about TSH level, especially for those taking T3. Is it ok for TSH to be very low – as a lot of doctors want you to reduce thyroid medication when it is?
A5:
If FT3 is not high, and you have hypothyroid symptoms remaining, you are not hyperthyroid. If FT3 is low and you still have hypo symptoms then you cannot be hyperthyroid – regardless of TSH.
What about people with central hypothyroidism that have a pituitary gland that never has anything but low TSH? Do those people have hyperthyroidism even though their FT3 is low? No of course they don’t. Doctors always work on the assumption that the pituitary is perfectly accurate. The scientific reality is completely different.
The pituitary gland is a very small spherical gland that has only the view of the FT4 and FT3 that flows into it in the bloodstream. It is also one of the best converters of FT4 to FT3 in the body as it makes both the D1 and D2 deiodinase enzymes. The pituitary has the highest concentration of FT3 out of all the glands and tissues in the body. So, the pituitary’s only view on your thyroid status is what it sees inside its own little sphere and it has no idea if the rest of your body is hypo or hyper. The pituitary gland cannot see inside your brain, your liver, your digestive system, your cold feet and hands etc.
In addition to the above, every other gland, organ, body tissue we have can have malfunctions. We might need to wear glasses, or hearing aids. We have digestive system disorders, liver issues, thyroid gland issues, diabetes, joint problems … you get the picture. Why do doctors think the pituitary gland, with its already extremely limited perspective, can always be absolutely spot on correct? Nonsense – it is not always correct.
Plus, when people take thyroid medication, and especially T3, this changes the normal balance of free hormone levels in order to compensate for any lost conversion ability of T4 to T3. This also confuses the normal algorithm the pituitary uses to assess the hormones and produce a TSH level. The more T3 we take the more likely TSH will be suppressed. It just isn’t designed to work like this. The level of TSH produced, even by a non-malfunctioning pituitary gland is designed for those with healthy thyroid glands and normal-for-them thyroid hormone levels. TSH needs to be ignored to a certain extent when someone is on thyroid meds. This is especially true if the person is still hypothyroid and has low / sub-optimal FT3, or they are on a fair amount of Liothyronine (T3). Even on T4-based meds, with poor conversion, often the T4 dosage has to be raised very high in order to create enough FT3 to stop the patient being hypothyroid. TSH often is suppressed in these cases too.
Many patients can never get well and on enough thyroid medication if TSH is used to limit their medication level.
Even given the above arguments, patients still occasionally ask me for peer-reviewed research papers that show why a low TSH is safe. It might seem a reasonable question on the surface but when you think more deeply about it several aspects are problematic:
1) Peer review is no longer a guarantee of the quality of the research and the experimental quality.
2) Most research on suppressed TSH requires high levels of thyroid hormones to do the suppression. The contention by many researchers, and myself, is that it is excess thyroid hormone that causes issues like atrial fibrillation (AFib) and bone loss, not low TSH. So, any experiments done like this must be immediately discounted.
3) There is already research that shows that low TSH itself is not an issue.
4) The only proper experiment with humans to see if low TSH causes issues in a population would be to engineer low TSH in a set of subjects that have normal-for-them thyroid hormone levels. So, this would involve having two sets of subjects:
a) a set of control subjects with in range TSH and normal-for-them thyroid hormones, and
b) a set of subjects with TSH levels engineered to be suppressed to zero, whilst their thyroid hormone levels are artificially maintained at the normal-for them-levels. Now, whilst some medications are known to lower TSH, e.g. steroids, they are unlikely to suppress TSH, plus they have effects on the heart and bones independently. So the only way I can think of to do this would be to surgically change the pituitary gland to have no TSH generating capability, without affecting other hormones. This is both unethical and near impossible to do.
Apart from hyperthyroidism, one of the reasons that some doctors have jumped to the conclusion that there is a link between low TSH and bone turn-over is that because bone cells express a functional TSH receptor on their surface. So, the TSH can connect to this receptor. However, any potential TSH effect is interwoven with other signals such as by thyroid hormones and estrogens,. There is redundancy in the system. This means what happens is highly depends on the specific condition and combinations, not a sole influence. It is also very difficult to isolate the TSH effect, because it is not the same to everybody. Furthermore, it is extremely difficult to create a proper experiment when thyroid hormones and estrogens are all perfect yet TSH is low. There has to be an individualised approach, as outlined in the following review – this was peer reviewed btw.: Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Individualised requirements for optimum treatment of hypothyroidism: Complex needs, limited options. Drugs Context. 2019;8:212597. doi:10.7573/dic.212597
Many of the other so-called ‘research papers’ on TSH and issues, seem to have just focused on TSH and not accounted for the reason the TSH is suppressed – hyperthyroidism. For the patient with low TSH, the doctors are often not accounting for whether the thyroid patient is well treated for hypothyroidism in terms of the right balance of T4 and T3 medication for them. They also often ignore status of the patients estrogen levels.
I come back to the point that when a patient is still hypothyroid, or is only on enough thyroid medication to resolve symptoms, and FT3 is not high, then TSH is not something to be concerned over, if the patient is well and other hormone levels are good. e.g. estrogen.
Patient’s Final Comments: This reminds me of a recent case study I read on a neuro-endocrinologist’s page (I never knew that was a thing). He had a woman he was treating with T3 who only felt good on HIGH doses of T3 but her heart rate was too high, otherwise ALL her other symptoms were gone. He kept her on the high dose stating there are receptors that don’t need as much T3 while other receptors do need it in certain instances. She was placed on a beta-blocker for her heart with cardiologist approval and is doing fantastic on her higher dose. I was shocked to see a specialist doing this.
Paul’s Final Comments: Well, I can’t comment on the individual case, but it is possible that this can happen. If so, then good for him! He was not restricted by current dogmatic practices.
My original blog post on multi-dosing of T3 is here for reference: https://paulrobinsonthyroid.com/why-t3-or-liothyronine-is-usually-taken-in-multi-doses-per-day/
I hope you found the above useful.
See my Recovering with T3 book for comprehensive information on using T3. See my The Thyroid Patient’s Manual book for a broader review of thyroid hormones, diagnosis and treatment using all the different thyroid medication.
Best wishes, Paul
