It is desperately clear to thyroid patient support groups and to many well-informed thyroid patients that there is an urgent need for a new paradigm in the treatment of hypothyroidism.
The Cambridge English Dictionary defines ‘paradigm’ as:
“A model of something, or a very clear and typical example of something“
We need a new, effective, and very clear model of how doctors should be using thyroid labs, using symptoms & signs, and how they should be treating thyroid patients. This new paradigm has to include all thyroid treatments, including T4, T4/T3, NDT, T3-Only.
This new model of treatment has to take into account the individuality of each patient. We are not robots that have come off the end of a production line. We do not have identical requirements for thyroid hormone replacement. Each of us needs to have the right level of thyroid hormones for us. The variation between thyroid patients of required FT4 and FT3 levels for good health is too large to attempt to treat everyone using the same protocol.
We need a new paradigm for thyroid treatment!
Why do I assert this so firmly?
Well, the answer to that comes from several sources of information. Let me discuss each of these. I’ll try and divide the points into several categories. But I will still number the points within each category to make them easier to refer to.
I also wanted to put many of the relevant research articles together in one document and link them to the various flawed aspects of current thyroid treatment. Hopefully, this will be of use to thyroid patients as they try to persuade their own physicians to provide the treatment that they require in order to get well.
Research regarding the current use of thyroid laboratory tests
1) TSH is not a measure that can be used to assess whether a thyroid patient is properly treated or not. The TSH laboratory test result does not track symptom improvement, as medication level or type is adjusted. It provides little or no guide as to whether the thyroid dosage is correct.
See references 1, 2, 3, 4, 16, 18, and 19 at the end of this article.
2) TSH can be suppressed (at or near zero) when a patient is on thyroid treatment. This does not mean the patient is hyperthyroid at all. It simply means that the TSH from the pituitary is suppressed. Endocrinologists and doctors are mistakenly applying the reasoning that suppressed TSH means hyperthyroidism, based on people who are on no thyroid medication at all! An individual suffering from hyperthyroidism, who is on no thyroid medication, will have a suppressed TSH and typically high FT3 and high FT4, due to excess thyroid hormone production.
However, the concern over suppressed TSH for hypothyroid patients already on thyroid treatment is misplaced. If this flawed reasoning is applied to thyroid patients on treatment, it may well stop them from getting enough thyroid medication and keep them symptomatic.
See references 2, 5, 6 and 15 at the end of this article.
3) FT4 & FT3 lab ranges are wide population ranges. A thyroid patient’s personal FT4 and FT3 ranges are less than half as wide as the lab ranges. So, when a doctor is assessing a patient’s lab results against the lab ranges, he has no idea if the results are in the right place for that individual patient. This makes reliance on thyroid lab results as the prime decider of correct treatment dubious at best. Thyroid patients on treatment with T4 medication have also been shown to have lower FT3 levels than healthy people. Since the test results for these people are included when laboratories construct the reference ranges this will influence the bottom and the top end of the FT3 lab range, making them lower than they ought to be for healthy people.
See reference 7 at the end of this article.
4) FT4 does not track symptom improvement as the patient’s medication level is adjusted. Just like TSH, The level of FT4 provides little or no guide as to whether a thyroid patient’s dosage is correct.
See reference 5 at the end of this article.
5) FT3 laboratory test results do track symptom improvement during the adjustment of thyroid medication. It is the only lab that goes up as symptoms improve. This should be no surprise at all to those thyroid patients who now realise that it is the T3 thyroid hormone that is biologically active and does all the good things for us within our cells. The big problem here is that FT3 is the one lab test that many doctors do not test! Madness!
FT3 is the most important lab test to do. Of course, if doctors do not test FT3, they will not see the issue and they can carry on looking at nice, in range TSH and FT4 results. They can keep telling thyroid patients that they are correctly treated, even though they are still very ill!
See reference 5 and 17 at the end of this article.
Levothyroxine (T4 medication) leaves some patients ill and symptomatic
6) Previous clinical trials comparing T4 to T4/T3 treatment were flawed. They were subject to amalgamation problems (Simpson’s paradox). They were not designed correctly and were always liable to conclude that T4/T3 offered no benefit.
Unfortunately, clinical trials are not the best way to assess medications as they lack the subtlety that occurs when a doctor is working with a patient to titrate medication correctly. For example, the Federal Drugs Administration (FDA) places actual experience of drugs in the hands of physicians as more important than the proof of effectiveness under clinical trials because clinical trials can be fraught with issues.
See reference 8 at the end of this article.
7) Research already exists that shows that some people will never recover using T4 medication alone. There are some good reasons for this.
See references 9 and 10 at the end of this article.
8) There are good reasons for adding T3 to therapy.
We know that the thyroid gland is typically responsible for around 25% of our T3, although this can vary a lot in some individuals. This T3 is produced by a healthy thyroid, primarily through the conversion of the T4 in the blood flowing through it. Consequently, any thyroid tissue damage through Hashimoto’s, or through the removal of all or part of the gland, will lose significant ability to convert from T4 to T3. T4 treatment may struggle to provide sufficient T3 to overcome symptoms.
Research has shown that athyreotic (thyroid-less) patients usually require sufficient T4 medication to completely suppress TSH before they ever get a high enough FT3 level to resolve their symptoms. In other cases, T4 alone is not enough to raise FT3 and additional T3 medication is needed. In many cases, TSH may need to be very low or suppressed.
The loss of thyroid gland tissue not only loses a large amount of conversion capability but importantly it loses the ability of the thyroid to act as a control system in managing thyroid hormone conversion and balance. This loss can occur through any form of thyroid tissue damage, e.g. thyroidectomy or Hashimoto’s. Losing some or all of a healthy thyroid gland has a profound impact on T3 levels that often cannot be compensated for by the conversion of Levothyroxine (T4) medication.
Moreover, we know from research that some people have genetic defects that can also reduce the capability to convert from T4 to T3 (DIO1 and DIO2 gene defects).
See references 4, 9, 12, 13 and 17 at the end of this article.
9) Many doctors and endocrinologists all over the world have treated patients successfully using mixtures of T4/T3 and even with T3-Only. The evidence is already there for the use of many different types of thyroid medications: T4, T4/T3, NDT, T3, Slow release T3.
The proof for the inclusion of T3 in treatment for some patients is already out there! This comes from both research findings and clinical experience with T3 in combination therapy (T4/T3 and NDT) and on its own.
See references 1, 6, 11, 14 and 17.
Symptoms & signs should be paramount
10) Clinical presentation is more important than laboratory test results. If we are going to have thyroid treatment that leaves fewer patients dissatisfied, doctors need to begin by focusing far more on the patient in front of them using symptoms and signs, with laboratory test results in a supporting role.
See references 1 and 11.
11) Endocrinologists and doctors are trying to force every thyroid patient into a little standard box.
This box contains T4 medication, the TSH and FT4 lab tests and very little else. It contains very little compassion for the suffering of the patients. Symptoms and signs are not at the forefront of the doctors’ minds when assessing the treatment. These are often dismissed as being caused by something else, e.g. depression, not exercising enough, Chronic Fatigue Syndrome etc.
This constricted, flawed treatment paradigm is simple and fast to use for the endocrinologists and doctors who have adopted it. They can get their patients in and out of their offices very quickly, without having to consider whether the medication is high enough, or contains the right blend of thyroid meds. This flawed paradigm is a ‘blessing’ in terms of time management for the doctors concerned. However, it is harming thyroid patients all over the world!
The experience of thyroid patients is clear – T3 & T4 medications are both needed
12) We know from an immense body of thyroid patients that many of them need different medications to get well: T4, NDT, T4/T3, or in some cases T3-Only. Thyroid patient experience is clear and we should not need to keep shouting this. It is so obvious to us.
Lab reference ranges are based on healthy people or thyroid patients on T4
13) This point is likely to be more contentious but I put it here because I believe it to be absolutely true.
Once a thyroid patient is on a combination of T4 & T3 treatments, the laboratory reference ranges break down. The ranges are based on people with no thyroid issues or those on T4 treatment. They are not based on those on combined T4/T3 or T3-Only. Most people whose blood is used to determine the lab ranges have either no thyroid issues, or they are on T4 treatment.
When a patient is on T4/T3, especially when the T3 content becomes a significant percentage, everything changes. The individual often has less T4 than someone on T4 therapy – because the T4 level frequently has to be lowered. The individual often has high peak levels of T3 in the blood – because a T3 dose peaks in the blood at around 2.5 hours and may stay elevated for a considerable number of hours afterwards.
We know from research, that many patients on T4 have lower FT3 than healthy people. My view is that the current lab ranges are biased downwards in terms of the lower limit of FT3 (due to thyroid patients on T4 therapy contributing to the construction of the FT3 range). The top of the FT3 range will be biased down for the same reason.
The other thing that happens is that the patient has less on-going T4 to T3 conversion within the cells (because they have less T4). This means that they need extra T3 medication to replace this missing converted T3. The converted T3 within the cells cannot be seen on a blood test BUT the extra T3 medication can. So, the more T3 in the T3/T4 combination that the patient has, the more the top of the FT3 range will become an unfair constraint.
I believe that the top of the FT3 range is too low for those on T4/T3 and definitely too low for those on T3-Only. I know many people on T3-Only medication who often have had FT3 results slightly above the top of the FT3 reference range, and they are healthy and definitely not hyperthyroid. I am one of these people.
Why would the ranges that have been developed based on non-thyroid patients or those on T4 meds be applicable to those with T3 in their treatment? There is no reason that they would. Being on different mixes of medication (less T4 and more T3) is likely to change the balance. Why assume that these ranges are the same for all types of treatment? It is a massive assumption. I believe that it is an incorrect one.
It is not reasonable to hold a thyroid patient’s T3 medication level down in order to satisfy the need to keep FT3 within the range if the patient has no indication at all of being over-medicated. On T3-Only in particular, the patient often has to have FT3 above the top of the range before they feel well (for good reasons I have explained in my books and on my website).
Summary of the above
The current paradigm of thyroid treatment is well and truly broken. Scientific research, patient experience, and some physician experience is evidence of this. Logic is screaming that the current approach is flawed in many ways.
The consequence of the current broken treatment approach is the really sad aspect of all of this. Thyroid patients are being left improperly treated in a large number of cases. I know. I talk to many of these thyroid patients every day. They are either on the wrong medication for them, or they are being left under-medicated – often both. Often they are not even having the right thyroid tests done and FT3 is not being monitored.
Many patients have severe symptoms, and are often left with them for years.
This broken paradigm is harming patients all over the world!
We need a new paradigm for the treatment of hypothyroidism. I describe this new paradigm very clearly in my latest book, ‘The Thyroid Patient’s Manual’.
Here are the key points:
- TSH can be totally suppressed when on thyroid treatment, i.e. near zero. This is fine and it does not mean the patient is hyperthyroid. So, keeping someone to an in-range TSH may leave them under-medicated.
- TSH does not track symptom improvement. So, a doctor cannot see a change in T4 medication and a lowering of TSH and assume that the patient is doing better.
- FT4 does not track symptom improvement either. A higher level of FT4 does not mean that the patient will be feeling better.
- FT3 does track symptom improvement but this is not the measure that most doctors focus on. This needs to become the most important of the lab tests performed.
- The reference ranges for FT4 and FT3 are wide population ranges. Real individual reference ranges (which cannot be known before treatment) are less than half as wide as the wide population ranges for FT4 and FT3. Doctors cannot conclude, just because a patient has FT4 and FT3 numbers in the range, that they are now correctly treated.
- Reverse T3 (rT3) may or may not be an issue, and there is definitely no ideal FT3/rT3 ratio for all patients. Just as the lab ranges are wide population ranges, people all have their own individual requirements for their labs. No ratio or reference range can be applied to all people. Very high rT3 is usually an issue. It can impact T4 to T3 conversion and may be a flag that the D3 deiodinase enzyme is high (which may block T3 action) but that is about all you can say about it. Symptoms and signs of the patient say more.
- T4 does not work for all patients. Some patients cannot get well using T4 medication. This is clear. Doctors need to realise this and be prepared to use the full range of thyroid medications. Even if this means they need to spend more time with individual thyroid patients and not just whisk them out of their office in five minutes!
- We also know that the thyroid gland itself is typically responsible for around 25% of our T3 (more in some people), mostly through conversion, so tissue damage through Hashimoto’s, or through the removal of the thyroid, loses a huge amount of ability to convert from T4 to T3. This can often not be compensated for with T4 alone. Doctors must expect to push up the dosage of thyroid medication or consider adding T3 treatment in these situations.
- We know from research that some people have genetic defects that reduce the capability to convert from T4 to T3 (DIO1 and DIO2 gene defects). This needs to be taken into account.
- We know from an immense body of thyroid patients that many of them need different medications to get well: T4, NDT, T4/T3, or in some cases T3-Only. All the thyroid medications must be on the table. If one fails to work, another must be offered. Doctors and thyroid patients need to start working in partnership with thyroid treatment. It seems that this can be more of an adversarial relationship compared with other health issues. Time for a change!
- Once a thyroid patient is on a combination of T4 & T3 treatments the laboratory reference ranges can break down. The ranges are based on people with no thyroid issues or those on T4 treatment. They are not based on those on combined T4/T3 or T3-Only. It is not reasonable to hold a thyroid patient’s T3 medication level down in order to satisfy the need to keep FT3 within the range if the patient has no indication at all of being over-medicated. On T3-Only in particular, the patient often has to have FT3 above the top of the range before they feel well.
Doctors need to stop treating us as if we are all the same. We are not identical robots. We have individual needs which the current broken process does not account for.
It is absolutely necessary at this time to move to a new paradigm of thyroid treatment!
The current, flawed approach is harming thyroid patients everywhere!
“Time for a reassessment of the treatment of hypothyroidism”
John E. M. Midgley, Anthony D. Toft, Rolf Larisch, Johannes W. Dietrich & Rudolf Hoermann.
BMC Endocrine Disorders volume 19, Article number: 37 (2019)
“Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment.”
Hoermann, Midgley, Larisch, Dietrich.
Front Endocrinol 2015 Nov 20;6:177. doi: 10.3389/fendo.2015.00177.
Full article: https://www.frontiersin.org/articles/10.3389/fendo.2015.00177/full
“TSH Measurement and Its Implications for Personalised Clinical Decision-Making”
Rudolf Hoermann and John E. M. Midgley
Volume 2012 Article ID 438037 https://doi.org/10.1155/2012/438037
“Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment”
Rudolf Hoermann, John E. M. Midgley, Rolf Larisch and Johannes W. Dietrich
Front. Endocrinol., 22 December 2017 https://doi.org/10.3389/fendo.2017.00364
“Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer”
Rolf Larisch, John E M Midgley, Johannes W Dietrich, Rudolf Hoermann
Exp Clin Endocrinol Diabetes 2018; 126(09): 546-552
“Thyroid hormone replacement – a counterblast to guidelines”
J R Coll Physicians Edinb 2017; 47: 307–9 | doi: 10.4997/JRCPE.2017.401
“Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease”
Stig Andersen, Klaus Michael Pedersen, Niels Henrik Bruun, Peter Laurberg
The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 3, 1 March 2002, Pages 1068–1072,
“Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?”
Journal of Thyroid Research. Volume 2018 Article ID 3239197 https://doi.org/10.1155/2018/3239197
Rudolf Hoermann, John E. M. Midgley, Rolf Larisch, and Johannes W. Dietrich.
“Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine”
Joao Pedro Werneck de Castro, Tatiana L. Fonseca, Cintia B. Ueta, Elizabeth A. McAninch, Sherine Abdalla, Gabor Wittmann, Ronald M. Lechan, Balazs Gereben, and Antonio C. Bianco
Journal of Clinical Investigation 10.1172/JCI77588
“Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment”
Rudolf Hoermann, John E.M. Midgley, Adrienne Giacobino, Walter A. Eckl, Hans Günther Wahl, Johannes W. Dietrich, and Rolf Larisch
“Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options”
Hoermann, Midgley, Larisch and Dietrich.
Drugs in Context
“Dual control of pituitary thyroid stimulating hormone secretion by thyroxine and triiodothyronine in athyreotic patients”
Hoermann R, Midgley JEM, Dietrich JW, Larisch R.
See: The Adv Endocrinol Metab (2017) 8:83–95.
“Relational stability of thyroid hormones in euthyroid subjects and patients with autoimmune thyroid disease”
Hoermann R, Midgley JEM, Larisch R, Dietrich JW.
See: Eur Thyroid J (2016) 5:171–179.
“Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life”
Anam Tariq, Yijin Wert, Pramil Cheriyath, and Renu Joshi.
South Med J. 2018 Jun; 111(6): 363–369.
Published online 2018 Jun 1. doi: 10.14423/SMJ.0000000000000823
“Biochemical markers reflecting thyroid function in athyreotic patients on levothyroxine monotherapy”
Ito M, Miyauchi A, Hisakado M, Yoshioka W, Ide A, Kudo T, Nishihara E, Kihara M, Ito Y, Kobayashi K, Miya A, Fukata S, Nishikawa M, Nakamura H, Amino N.
Thyroid. 2017;27:484-490. doi:10.1089/thy.2016.0426
“Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy?”
Sarah J. Peterson, Elizabeth A. McAninch, Antonio C. Bianco
The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 12, 1 December 2016, Pages 4964–4973,
“Defending plasma T3 is a biological priority”
Sherine M. Abdalla and Antonio C. Bianco
Clin Endocrinol (Oxf). 2014 Nov; 81(5): 633–641.
Published online 2014 Aug 7. doi: 10.1111/cen.12538
“Does TSH Reliably Detect Hypothyroid Patients?”
Ling C1, Sun Q1, Khang J1, Felipa Lastarria M1, Strong J1, Stolze B1, Yu X1, Parikh TP1, Waldman MA1, Welsh K1, Jonklaas J2, Masika L3, Soldin SJ1,2.
Ann Thyroid Res. 2018;4(1):122-125. Epub 2018 Feb 20.
“TSH Should not be used as a Single Marker of Thyroid Function”
S. Soldin, Qian Sun, Brian Stoize