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Thyroid UK
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BTF Research Award 2018 to Prof Colin Dayan for: Morbidity And Mortality In Liothyronine Treated Patients: LT3 Outcome Study


Thyroxine is the usual treatment for people with an underactive thyroid problem. Most patients who take thyroxine feel well on this. However a small proportion of patients do not feel well on thyroxine alone and some practitioners treat such patients with another drug called T3. Whether T3 works just as well as thyroxine remains to be proven and opinions are divided on this. However, a growing number of patients are prescribed T3, mostly from unregulated or independent medical practices. This is worrying because the long term safety of T3 has not been established and current guidelines written by medical professionals do not advocate its routine use in practice.

The current study proposes to investigate whether patients who receive T3 have a greater long term risk of heart problems, strokes, and death when compared to those who are treated in the standard way with thyroxine.

We plan to carry out this investigation using data from the private clinic records of the late Dr Gordon Skinner comprising the details of over 3,000 patients treated over a period of 20 years. Since Dr Skinner’s death, the Vaccine Research Trust that he established has been the Custodian of the clinic data. Via the Vaccine Research Trust the data from these patients will be linked anonymously to information held in the NHS Health and Social Care Information Centre (HSCIC) regarding hospital admissions from heart disease and strokes as well as information on death. We will then compare this data to similar data in individuals that have only received LT4. We will be able to do this without knowing the identities of any of these patients or any identifiable health records going outside of the Vaccine Research Trust . On this basis, individual patient consent is not required.

Our study will be of importance to patients with thyroid disease. An increasing number of patients are asking for a trial of T3 or NDT therapy and attending private clinics, but the risks to patients of heart disease, strokes, and death with of this practice are unknown. If there is a significantly increased risk, as many endocrinologists suspect, then patients need to be made aware of the facts. On the other hand if the risk is not different from patients taking LT4 then it will allow us to undertake further trials to try and understand if LT3 could benefit patients with an underactive thyroid problem.

Thanks to DippyDame for bringing this to our attention! :)

15 Replies

If there is a significantly increased risk, as many endocrinologists suspect, then patients need to be made aware of the facts.

Yes - the risk should be identified - and balanced against the risk of, usually, levothyroxine monotherapy and the downsides so often reported. The patients should be made aware in an accurate, honest and proper way. And it should STILL be the decision of each and every individual patient which route to take.

It should not be handed down from on high - Thou shalt not take liothyronine. There are only ten commandments - all of which are already well-established.

Television soaps are chock full of scenes where patients are informed of their choices and asked to make their decisions. Let us see it happen in the thyroid world.


In fairness, what should be done is to compare outcomes on T4 only with Skinner's data on T3. Then we can get a true estimate of whether or not any or all thyroid hormone treatments have consequences, and how they compare against each other. I don't know if such work has been done for T4 only, but it has to be an important part of the perceived outcome.


It's great that they are doing this research. However, Dr Skinner treated a number of thyroid disorders not just primary hypothyroidism (elevated TSH, low fT4). These other disorders are largely unidentified and carry higher inherant risk, so it's important they don't compare apples with oranges. Also, many of his patients were left hypothyroid for years with attendant damage to their long term health.


Pardon my ignorance, but if T3 is so dangerous, why is produced naturally in people who do not have thyroid problems? I would have thought that was an indication that it was necessary. So if it is necessary, what about us, who no longer have a working thyroid and also have conversion problems? How can it be right that giving us T3 is more dangerous than us not having any T3?


I agree, great that some relevant research is imminent . My heart does miss a beat so to speak when I read this:

'However a small proportion of patients do not feel well on thyroxine alone and some practitioners treat such patients with another drug called T3'.

Just how small a portion? There seem to be droves of folk on this forum. Yes there may be risks with T3 treatment but at least let's try and establish some empirical evidence and I agree with those who say what about the risks of ineffective thyroid treatment, possibly exacerbated by years of neglect or ignorance.


This reads as if they don't really know what T3 is. For a start, it isn't a drug - and neither is T4 (levo). It's written as if T3 is just another version of T4, like aspirin and codeine are two different versions of pain killers. It really does not give me hope that any research they do will be informed and unbiased.


Any substance that has a physiological effect is classed as a drug, such as insulin or levothyroxine. This team will do good research but it depends on the objective of the study and whether they consider what Dr Skinner was treating which in general was not simple primary hypothyroidism. On the plus side it is quite remarkable that the BTF is funding a study into Dr Skinner's work. This would never have happened in the past, it really is quite an advance that is to be welcomed. I know they have a long way to go but at least it is a start.


Hmmm... Well, that's stupid! Are you sure about that? I know it's so in the US, but in the UK?

I know it's a step forward in some ways, but could result in a step back in the end! I just find it rather worrying.


I'm fairly sure. There doesn't seem to be a formal definition of a drug but for example substances such as liothyronine come under the Prescription Cost Analysis which refers to 'drugs' and they are in the BNF which is a list of drugs. I guess it's comes down to common usage rather than a formal definition like one sees in e.g. mathematics. Liothryonine (as opposed to T3) is a drug because it has excipients, it's not pure T3. The same would apply to NDT such as Armour which also has excipients. I also have concerns about the study, I would like a clearer objective and a comparison of treated and untreated patients (those told they have ME). I welcome the study, thousands of BTF members will get to hear about Dr Skinner which has to be good.


I was told that the difference between a drug and a hormone was that a drug changed bodily functions, and a hormone just restored the body's equilibrium. But, the reason I said it was silly calling it a drug is that it puts the wind up people when they find out they have to take it for life - and who can blame them!

Yes, I totally agree with you about the study. All that needs to be out in the open. But, shining the spotlight on Dr Skinner would be a positive. Or should I say 'could be' a positive...


Funny how older women are offered hormone replacement therapy (HRT) where the actual hormone content is left vague, whereas in thyroid treatment we are given "the drug" levothyroxine. Indeed, much of the use of women's hormones seems intentionally made to sound uncontroversial, even soft, gentle and warm. It couldn't be intentional, could it?


Not quite sure how to react to that. Because hypo is considered to be - unrealistically - a 'woman's disease', and the treatment is levo.

And not all women are offered hormone replacement therapy. I never knew when my menopause was, because I didn't have any symptoms, but probably 10 + years later, I was prescribed progesterone cream where the hormone content was precise. So, I've not had any soft, warm, gentle feelings. However, I would venture to suggest that it's more a question of ignorance on the part of doctors, than any intent to put women at ease! But, that's always my response, isn't it. lol


A long-term (17 year) study has been done and recently published.



To look at adverse outcomes for patients on liothyronine compared to l-thyroxine. Some trials have examined the relative merits of liothyronine but none have looked at adverse outcomes in large numbers.


An observational study of all patients prescribed thyroid hormone replacement in Tayside Scotland (population 400 000) from 1997 to 2014.


A study group of patients having ever used liothyronine (n = 400) was compared to those who had only used l-thyroxine (n = 33 955). All patients were followed up until end-point, death or leaving Tayside.


Mortality rates and admissions with cardiovascular disease, atrial fibrillation, fractures, breast cancer and mental diseases were compared. Incident use of bisphosphonates, statins, antidepressants and antipsychotics was compared.


Compared to patients only taking l-thyroxine, those using liothyronine had no increased risk of cardiovascular disease [hazard ratio (HR) 1·04; 95% CI 0·70-1·54], atrial fibrillation (HR 0·91: 0·47-1·75), or fractures (HR 0·79: 0·49-1·27) after adjusting for age. There was no difference in the number of prescriptions for bisphosphonates or statins. There was an increased risk of new prescriptions for antipsychotic medication (HR 2·26: 1·64-3·11 P < 0·0001) which was proportional to the number of liothyronine prescriptions. There was a non-significant trend towards an increase in breast cancer and new use of antidepressant medications. During follow-up, median TSH was higher for patients on l-thyroxine alone (2·08 vs 1·07 mU/L; P < 0·001).


For patients taking long-term liothyronine we did not identify any additional risk of atrial fibrillation, cardiovascular disease or fractures. There was an increased incident use of antipsychotic medication during follow-up.

The abstract is here: ncbi.nlm.nih.gov/pubmed/269...


A series of comments have removed.


It would be interesting to see the outcome of patients with many hypothyroid symptoms, but no treatment whether T3 or T4. One would have to be careful that the patient wasn't already suffering problems because their GPs/Endocrinologists would not prescribe thyroid hormone replacement. What comes first, the chicken or the egg??


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