Thyroid - the correct prescribing of thyroid hormones
(By Dr Sarah Myhill and Craig Robinson)
Stylistic note: Use of the first person singular refers to me, Dr Sarah Myhill. One can assume that the medicine and biochemistry are mine, as edited by Craig Robinson, and that any classical and mathematical references and quotes or historical and linguistic notes are Craig’s!
There are four reasons why UK citizens are not subject to "best practice" with respect to prescribing thyroid hormones. All relate to the prescribing of thyroid hormone for under-active thyroid glands (hypothyroidism).
The threshold for thyroid stimulating hormone (TSH) is set too high.
When levels of thyroid hormones in the blood start to fall, the pituitary gland increases its output of thyroid stimulating hormone (TSH), which kicks the thyroid into life and increases output of thyroid hormones. If the thyroid gland starts to fail, this is reflected by levels of TSH rising. The question is at what point should the prescription of thyroid hormones begin?
The normal range for TSH in this country varies enormously from one laboratory to another. This means in some locations in the UK a thyroid prescription would not be given until the TSH rose above 5.0mlU/l.
As a result of research, the normal range for TSH in America has now been reduced so that anybody with a TSH above 3.0mlU/l is now prescribed thyroid hormones. This research has shown that people with a TSH above 3.0mlU/l are at increased risk of arterial disease (a major cause of death in Western culture), insulin resistance (and therefore diabetes), inflammation and hypercoagulability (sticky blood). Indeed, there is a recommendation afoot in America to further reduce the threshold for prescribing to 2.5mlU/l.
What is completely illogical is that in UK the target TSH level for patients on thyroid replacement therapy is often stated as being less than 2mlU/l or even less than 1.5mlU/l. This is a ridiculous anachronism given that prescription is not recommended until levels exceed, say, 5.0mlU/l! So, someone could have a level of 4.0mlU/l and not be receiving thyroid replacement therapy (because their level is not above 5.0mlU/l), whereas if someone was on thyroid replacement therapy, a level of 4.0mlU/l would be considered much too high and would need to be brought down to below 2.0mlU/l or even 1.5mlU/l!
We should amend the threshold for prescribing thyroid hormones to 3.0mlU/L or better still 2.5mlU/l.
There is a further inconsistency in BTA (British Thyroid Association) guidelines. The level of thyroid hormones in pregnancy is critical for foetal development. For pregnancy the target for TSH is a level below 2.5mlU/L. Furthermore requirements during pregnancy increase, so thyroid function should be checked every three months. What is the logic of only prescribing thyroid hormones to a non-pregnant woman with a TSH of above 5.0mlU/l but if pregnant the prescribing of thyroid hormones would start when levels exceed 2.5mlU/l?
Dr Kenneth Blanchard states that reliance on a TSH to diagnose hypothyroidism is the biggest single medical error of modern times. It has resulted in millions of people missing out on this safe, life transforming, disease preventing treatment.
Population normal range versus individual normal range - they are not the same
The population normal range for levels of thyroid hormone in the blood is not the same as the individual normal range. We differ as individuals in our biochemistry as we differ in our looks, intelligence and morphology. This biochemical variation should be taken into account when it comes to prescribing thyroid hormones.
The population normal range of a Free T4 is 12 - 24pmol/L. A patient, therefore, with blood levels of 12.1 would be told they were normal because they are within the population reference range. But actually that person's personal normal range may be high. They may feel much better running a high T4 of say 22, i.e. nearly twice as much but still within the population reference range.
Research done originally in UK, and now repeated in America, clearly shows that the individual normal range of thyroid hormones is not the same as the population reference range. In order to find out who these individuals are, patients have to be assessed clinically as well as biochemically. In actual UK clinical practice this is rarely done except by a few physicians conversant with this issue.
Some people feel better on different preparations of thyroid hormones
In theory, if the patient has been shown to be hypothyroid, then all their symptoms should be improved with synthetic sodium thyroxine. In practice, this is not always the case - there is no doubt that clinically some patients feel very much better taking biologically identical hormones such as natural thyroid (a dried extract of pig thyroid gland which is a mix of T4 and T3). Indeed, before synthetic thyroid hormones became available, all patients were routinely treated with natural thyroid. The purity and stability of these preparations has been long established, indeed much longer established than synthetic thyroxine!
Part of the reason why people feel better taking natural bio-identical hormones is that some people are not good at converting T4 (which is relatively inactive) to T3 (which is biologically active). However, this does not explain the improvement in every case. It is difficult to explain why there should be an additional effect, but for many people it is the difference between drinking cheap French plonk ( Plonk) and good quality Spanish Rioja ( Rioja) . The alcohol content is the same, but the experience completely different!
According to Dr A Toft, Consultant Endocrinologist, Edinburgh, “It would appear that the treatment of hypothyroidism is about to come full circle.”
“In patients in whom long-term T4 therapy was substituted by the equivalent combination of T3 and T4 scored better in a variety of neuropsychological tests. It would appear that the treatment of hypothyroidism is about to come full circle”. Ref: Endocrine Abstracts 3 S40, T3/T4 combination therapy. AD Toft, Endocrine Clinic, Royal Infirmary, Edinburgh, UK. Please see Endocrine Abstracts
Timing of dosing
I have learned much more from consultant endocrinologist Dr Kenneth Blanchard's book "The functional approach to treating hypothyroidism". (Amazon.co.uk link to "The Functional Approach to Hypothyroidism". He makes many useful clinical points:
- Thyroid hormones should be taken with food - he observes that cravings can be triggered by thyroid hormones on an empty stomach
- T4 (thyroxin) is slow acting and "base loads". It is the night hormone - we should split our daily dose into two. The evening dose should be taken with supper which should be at least 4 hours before bed time.
- By contrast T3 is the day hormone that wakes us up.
- Our requirements change with the seasons - in Nature TSH falls in winter so levels of T4 and T3 fall - this puts us into semi-hibernation and allows energy conservation by causing mild fatigue and depression with greater need for sleep. The reverse is true for the summer. In modern times with food and warmth aplenty the imperative to do this declines. However some people need more thyroid hormones in winter to prevent severe fatigue and depression. In this event Dr Blanchard suggests "jump starting" followed by a different maintenance dose - so for example in the Autumn someone taking 100mcgms of T4 would have a jump start of 150mcgms for 3 days then maintenance dose of 110mcgms. In the Spring one would do the reverse - stop T4 for 3 days then return to the usual 100mcgms per day.
Some people only feel well using pure T3
At present we do not have biochemical tests to predict who these people are! A reverse T3 test may help but may not. If symptoms are typical of hypothyroidism but not responding to T4 or T4/T3 mixes, then a trial of pure T3 may be in order. T3 is short acting and must be taken at least 3, possibly 5 times daily. The smallest size tablet is prescription only tertroxin 20mcgms (equivalent to 100mcgms of T4). A starting dose would be 10mcgms split into 3 doses - tricky! I suggest crushing half a tablet, and using a wet finger tip to take a third of the powder three times daily. One may know within a few days if this was making a difference but a proper trial would be a few weeks. For details, see Paul Robinson's excellent book on the subject - Recovering with T3: My Journey from Hypothyroidism to Good Health Using the T3 Thyroid Hormone. (Amazon.co.uk link to "Recovering With T3: My Journey from Hypothyroidism to Good Health Using the T3 Thyroid Hormone").
For more detailed discussion see Thyroid Hormone Transport where the importance of pure T3 is explained in terms of transport of T3 across cell membranes.
The correct proportion of T4 to T3
Dr Kenneth Blanchard maintains that the correct proportion is 98.5% T4 to 1.5% T3, for some a bit more, others less. Achieving this is difficult because armour thyroid is 80% T4 and 20% T3. He uses slow release T3 - not available in UK. However transdermal T3 could be an option - watch this space!
The timing of dosing with T3 may be critical
Paul Robinson, in his excellent book on T3, hypothyroidism and the Circadian rhythm (Amazon.co.uk link to The Ct3m Handbook) has made the interesting observation that our circadian rhythms, essential to health, are determined by when hormones are produced. Since they work synergistically we need them to be produced at the same time. Timing is triggered by the pituitary gland, the conductor of the endocrine orchestra! It starts with TSH levels rising sharply at midnight and is followed by increases in T4, T3 and cortisol later in the night. As they come together they trigger wakefulness. Paul found out for himself, and proved it to his satisfaction through blood tests, that his health was further improved by taking his morning dose of T3 at 5.30am. See his website Recovering with T3 for his account of this.
Initial improvement followed by decline
Dr Blanchard observed that some patients improved on thyroxin and then worsened. He describes a "sweet spot" of optimal levels of T4. He believes the reason for this is that TSH is partly responsible for converting T4 to T3 - so if levels of these hormones are too high, TSH is switched off and with that comes a switching off of T4 to T3 conversion. T3 is the day hormone that fires us up and because T4 is slow acting there may be a delay in noticing this "switch off" of T4 converting to T3 and this can be clinically very confusing.
Monitoring treatment just by using a TSH can be misleading
In his article (follow the link below in External Links) Peter Warmingham cogently explains how just a TSH is not a good way to monitor replacement therapy. It is vital to measure levels of free T4, ideally free T3 as well, and assess the patient clinically - ie how do they feel? Are there any clinical symptoms of under or over dosing?
Finally anyone who is hypothyroid for reasons other than autoimmunity, is likely to be iodine deficient. See Iodine - what is the correct daily dose?
Why are we seeing an epidemic of thyroid disease?
A whole range of chemicals have been shown to be goitrogenic (substances that suppress the function of the thyroid gland by interfering with iodine uptake) and/or suppressors of the HPA axis and/or suppressors of thyroid hormones uptake and/or suppressors of T3 uptake. These include perchlorates (washing powder), phthalates (added to plastics to increase their flexibility, transparency, durability, and longevity) and bisphenol A (in plastic wrappings), pyridines (cigarette smoke), PCBs and PBBS(fire retardants in soft furnishing), UV screens (sunblocks and cosmetics), and many others. For a full list see Oxford Medicine Chapter 3.2.2 Environmental Factors. A recent study showed that hypothyroidism was 30% more common in areas of fluoridated water - that makes perfect biological sense - fluoride is a smaller molecule which fits and blocks the iodide receptor. Please see Water Fluoridation A Critical Review of the Physiological Effects of Ingested Fluoride as a Public Health Intervention
- Iodine - what is the correct daily dose?
- Prescribing guidelines for thyroid hormones drawn up by the BSEM
- Water Fluoridation A Critical Review of the Physiological Effects of Ingested Fluoride as a Public Health Intervention
- Endocrine Abstracts by Dr A Toft
- Effect of Exogenous Thyroid Hormone Intake on the Interpretation of Serum TSH Test Results Article by Peter Warmingham with an Introduction by Dr. John C. Lowe, Editor-in-Chief of Thyroid Science Just click on "Full Text Free in pdf format" at the bottom of this webpage or click here
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