T3 and T4 combination treatments?

[Dany555]

I have Hashimoto’s diagnosed by an NHS endocrinologist. I could not tolerate levothyroxine at any dosage (the doctor tried adjusting the dose several times over a long period of time). I ended up taking myself off of levothyroxine as the side effects were intolerable.

A different doctor suggested I try a combination T3/T4 treatment. I am able to tolerate the combination treatment, it improves my symptoms and I do not have the horrible side effects that I got from Levothyroxine-only treatment. My bloods are tested every four months and have always been ‘in range’. I am aware of the risks but I accept these risks as I prefer reduced quality of life in later life rather than very poor quality of life for my whole life on levothyroxine-only.

I am concerned about the way that information about T3/T4 combination treatments is being presented to patients, GPs and presumably aspirant endocrinologists in training.

I would like to know:

1) Can you conceive of any limitations to the trials that showed no effect for T3/T4 combination treatments? Were all the trials to date perfectly designed and executed?

2) Where trials found additional benefits for combination treatments as compared to levothyroxine-only treatments or trials showed that patients preferred combination treatments, why are these findings ignored?

3) Are there ever any problems with relying on meta-analyses to inform your recommendations as opposed to analysing the study design and findings of the actual trials themselves?

4) Can you conceive of any ways in which it might be problematic to extrapolate data from RCTs to a real-life clinical setting where you have patients with their own individual genetic variations, metabolic needs, gender, age, comorbidities, allergies, preferences etc.? Do you ever question the external validity of RCT trials?

5) When weighing up treatment recommendations, in what ways do you quantify and qualify the harm done to those patients who either cannot tolerate levothyroxine or remain sick whatever the dose adjustment of levothyroxine?

6) Why are factors like quality of life and patient preference important in other areas of endocrinology like diabetology yet appear to be ignored in thyroidology?

Eg. Where meta-analysis shows little additional benefit for one insulin over another and a differing safety profile for those insulins, why aren’t diabetologists dictating that there is "only" one treatment for all insulin dependent diabetics?

[Dr Petros Perros]

Firstly, your case is rather different to many of the other postings that have been placed on the forum on the topic of T3/T4. You describe intolerance to levothyroxine alone, though interestingly you seem to tolerate it better presumably in a lower dose with T3. I think the way that you and your doctor has handled this is very reasonable, you have been pragmatic and have weighed out the benefits against the potential downsides and made an informed decision. Why you have not tolerated levothyroxine is unclear to me. True intolerance to levothyroxine is rare and can be tested for. This is of some importance because, if for instance the intolerance is to some of the other constituents of the tablet, there are ways round it. Clarifying this may have an impact on decision making about risks and benefits of being on combination versus monotherapy.

Your questions are all valid and relate to important issues of how medical evidence is evaluated and the processes that determine how that knowledge is applied to the individual patient. Well conducted randomised controlled trials are the best way of answering questions about whether a treatment is better than another. There are numerous examples in the history of medicine where bias has influenced results of trials and one has to be very careful in conducting studies and interpreting them. Experience of many years suggests that before one can have a reasonable amount of certainty, at least two RCTs conducted independently should yield similar results. Metanalyses are very valuable in appraising multiple RCTs. It is on this basis that huge advances have been made for example in the treatment of cancer. When the luxury of multiple RCTs all pointing in the same direction is lacking, then we have to deal with uncertainty. I think this is what you and your doctor have done successfully. There is no precise recipe for that in my view, though the essential ingredients are engagement by both physician and patient, understanding of options, risk and benefits and a will to resolve the problem.