I often get asked the question of whether it is safe to have zero (or suppressed TSH) when on T4/T3 treatment (or any thyroid treatment).
The research is very clear, but I wish more doctors and endocrinologists were aware of this research!
A suppressed TSH when on thyroid treatment is usually NOT a concern, as long as:
- The person has no hyperthyroid symptoms and
- FT3 is not above the range (but this last point also has caveats).
The above statement is true on T4, and even more relevant on treatment which includes T3. I will provide the research references below to back it up.
What about T4/T3 or T3-Only therapy?
Firstly, it is important to know that for those on treatment containing T3 (T3/T4 or NDT or T3-Only) TSH can easily be suppressed to near zero even though FT3 and FT4 can be in range. This is one of the flaws of the TSH test. Even Dr. Robert Utiger who created the TSH test in the first place acknowledged the highly suppressive effect of T3 containing medication. So, attempting to use TSH for those on T3 therapy in the same way as it is used for those on T4 medication is flawed.
The second point point here is that sometimes people need a high level of T3 in their medication in order to get well. In fact, on any T4/T3 based treatment, I believe FT3 can creep up to and over the range also. There is a very clever but a little complicated explanation for this. It goes like this:
People who are healthy, or on T4 medication, have on-going T4-to-T3 conversion happening within their cells. Much of this intra-cellular-T3 that is converted from T4 remains in the cells and is used there. Little gets returned to the bloodstream. This is an IMPORTANT point. The FT3 population reference range is created by measuring blood levels of FT3.
So, for people who are healthy, or on T4-therapy, they have the FT3 that can be measured. However, they also have the EXTRA FT3 that is being constantly converted from T4 within their cells.
So, the FT3 reference range does not account for the extra intra-cellular FT3.
As soon as someone uses T4/T3 treatment or NDT, they have extra T3, but usually less T4 than previously had. So, the FT3 measured in blood is almost certainly going to be higher for someone on T4/T3 therapy than someone on T4 treatment. There will also be less intra-cellular T3 being converted from T4. The net result is that T4/T3 therapy patients are much more likely to have a higher FT3 – possibly close to the top of the FT3 reference range.
The thyroid lab ranges have not been developed based on a population of thyroid patients who are on some T3 – so this should not be a surprise.
The situation gets a whole lot worse for people on T3-Only. They have NO intracellular T4-to-T3 conversion at all. Their FT3 level is often well over the range. This is necessary in order to compensate for the lack of intracellular T4-to-T3 conversion.
Our UK reference range for FT3 is typically 3.3-6.6. My FT3, when tested, is often at or above the top of the FT3 reference range. I have zero FT4 and zero TSH. I am NOT hyperthyroid. This makes lots of sense when you understand the real endocrinology.
Unfortunately, most doctors do NOT understand the fundamentals.
I hope this helps to explain it.
This is a great paper that describes that even on Levothyroxine only (T4-Only) therapy TSH can be low for some patients:
“Problems with the assessment of thyroid function and levothyroxine replacement levels in pituitary disease”
The Pituitary Foundation.
https://www.pituitary.org.uk/problems-with-the-assessment-of-thyroid-function-and-levothyroxine-replacement-levels-in-pituitary-disease/
In addition to all the above, some thyroid patients have central hypothyroidism. This means that either due to a maladjustment of the pituitary or hypothalamus that they tend to always have low TSH – even if their FT4 and FT3 are low. In these cases, it would be positively dangerous to attempt to use TSH to manage medication levels. The patient’s signs and symptoms must be the primary focus as well as FT3 and FT4 levels.
I said at the start that I often get asked questions about whether a low TSH is acceptable. This is a typical question from a patient, followed by my answer:
Patient: I have subclininal hypothyroidism. I take Levothyroxine & Liothyronine. All my doctors get freaked out at my very low TSH numbers and want to lower my Levothyroxine dose. Iām a bit skeptical.
My response: 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 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 that 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 or 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.
You are right to be sceptical – TSH can be very low and you may still be either on the right medication level, or even under-medicated.
Here is one final point on this subject, before I list some relevant research papers:
Patients 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 usually 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. The experiment would have to only have low TSH, with all other hormones and body chemistry unaltered. 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 is very difficult to isolate the TSH effect, because it is not the same to everybody. Furthermore, as explained above, it is near impossible 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 (also listed in the research references – 7). 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
Note: I realise that many patients have doctors and endocrinologists who refuse to have below reference range TSH. Even if the patient remains with severe hypothyroid symptoms that go away with more thyroid medication, many doctors will not allow TSH to go below the bottom of the reference range. They assert that low TSH will result in bone loss or heart issues and is unacceptable. There is research that disagrees with their views on TSH ā some of this is presented in this chapter. Plus, they ignore the fact that being severely hypothyroid is linked to cardiovascular issues, diabetes, depression and a host of other undesirable health issues.
Having said all this, no matter what research links or arguments are presented to some doctors and endocrinologists, there is often no shaking their opinion, so strong is the dogma that has developed during their training.
It is worth being aware that in some cases, no argument will work with some doctors. All I can do, is to present the alternative case. Many thyroid patients now refuse to have their health ruined by a doctor, or endocrinologist, who is content to leave the patient with severe hypothyroid symptoms. I know I would not hand my hormone health over to a doctor ever again ā I lost far too much by doing that, for too long, the first time.
For those patients that know they have a doctor, or endocrinologist, who is fiercely dogmatic about not allowing low TSH, there is one approach that can work. If the patient is certain that they are not hyperthyroid at all in terms of signs and symptoms, and they feel far healthier on the current dosage of thyroid medication, then private lab testing can be a help. By stopping thyroid medication, especially T3, for 18-24 hours prior to the private laboratory test of TSH and FT3, the patient can get the results and determine if this length of gap with no T3 medication is going to be sufficient to get TSH and FT3 in range. If it is still a problem, then it can be repeated with a longer gap. We should not have to do this. However, it is better than having the thyroid medication withdrawn or reduced.
Here are some further research papers that are referred to in Chapter 14 of The Thyroid Patient’s Manual:
1. “Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer”
Larisch, Midgley, Dietrich, and Hoermann.
https://www.researchgate.net/publication/322914153_Symptomatic_Relief_is_Related_to_Serum_Free_Triiodothyronine_Concentrations_during_Follow-up_in_Levothyroxine-Treated_Patients_with_Differentiated_Thyroid_Cancer
This paper clearly proves that FT3 concentrations are the most important in clinical decision making, as they are most closely linked to residual hypothyroid symptoms in T4- Only treated patients. It also shows that in-range TSH is not sufficient for symptom relief.
2. “Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment”
Hoermann R1, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R.
See: Clin Endocrinol (Oxf) (2014) 81:907ā915. doi:10.1111/cen.12527
URL: https://www.researchgate.net/publication/263321383_Homeostatic_Equilibria_Between_Free_Thyroid_Hormones_and_Pituitary_Thyrotropin_Are_Modulated_By_Various_Influences_Including_Age_Body_Mass_Index_and_Treatment
This is a great paper, although complex. It shows that it is the relationships of the thyroid hormones, and how they adjust during treatment, that counts. It also makes it crystal clear that TSH should only have a supporting role in the assessment process during treatment.
3. “Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment”
Hoermann, Midgley, Larisch, Dietrich.
https://www.frontiersin.org/articles/10.3389/fendo.2017.00364/full
This paper talks about the need for a new paradigm of thyroid treatment that accepts that the relationship between TSH and thyroid hormones are individual, dynamic and can adapt, i.e. the current practice of simply looking at numbers that do or do not fit in the population ranges is not sufficient.
4. Thyroid hormone replacement – a counterblast to guidelines – Dr A.D. Toft. See:
http://www.rcpe.ac.uk/sites/default/files/jrcpe_47_4_toft.pdf
5. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism – M P J Vanderpump, J A 0 Ahlquist, J A Franklyn, R N Clayton, on behalf of a working group of the Research Unit of the Royal College of Physicians of London, the Endocrinology and Diabetes Committee of the Royal College of Physicians of London, and the Society for Endocrinology See:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2351923/pdf/bmj00557-0041.pdf
6. A Dialogue with Utiger: T3 based thyroid therapy over-suppresses TSH – Thyroid Patients Canada. See:
https://thyroidpatients.ca/2019/09/10/a-dialogue-with-utiger-t3-over-suppresses-tsh/
7. 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.
See:
https://pmc.ncbi.nlm.nih.gov/articles/PMC6726361/
I hope you found this interesting.
Best wishes,
Paul
Updated 16th December 2024
