Levothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of the L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE).
Goal
To assess patient preferences in the treatment of hypothyroidism.
Methods
A systematic review, meta-analysis, meta-regression, and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs. L-T4+L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by four researchers.
Results
Eleven RCTs (eight cross-over studies) with a total of 1,135 patients were considered. Overall, 24% of patients preferred L-T4 versus 52 % who preferred L-T4+L-T3 or DTE; 24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (RR: 2.20, 95% CI: 1.38 to 3.52; p = 0.0009). Excluding four studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97, 95% CI: 1.52 to 2.54; p < 0.00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84, 95% CI: 1.50 to 5.39; p < 0.00001). Network meta-analysis confirmed the preference for DTE and L-T3+L-T4 versus L-T4 alone.
Conclusion
Patients with hypothyroidism prefer combination therapy (L-T3+L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism.
Given that those preferring LT4, or currently with no preference, could well change their opinions if allowed to trial a range of dosages and ratios, the 52% could actually just be a starting point.
This is the percentage of those in the studies which generally require a TSH > 10.0. If they studied those with symptoms of hypothyroidism and lower TSH there might be a much higher percentage.
With hindsight, I suspect I have been low in thyroid hormone for much of my life. No evidence because, of course, no-one goes to a doctor, nor gets thyroid tests, unless there is something to point in that direction. But things like almost permanent dry hands - which miraculously resolved with levothyroxine.
But I keep wondering about LT3. The issues I have are that maintaining a low dose, long-term, might be difficult or expensive. Though quite possibly, I'm one of those who converts just fine and might not benefit significantly.
100x 20mcg Thybon Henning is £60 privately with 1 off £50 appointments and 9 monthly £30 appointments ongoing. if you quartered those you have more than a years worth for £90 a year, less than £10 a month. Some spend more on streaming TV channels. Just saying…. 🌱
I'm not sure I have sufficient basis to persuade anyone I "need" T3.
I have never seen an endo (for myself).
And, before I even got to write this reply, we are seeing difficulties with that source. Despite it being entirely legal.
And I would very much prefer to try using low dose tablets (e.g. 5 microgram) so that even further subdivision would be possible. But without going down the custom/compounded route.
It is first that I don't want to change unless I can see an absolutely reliable route - forever. That is getting whatever prescription(s), dispensing, products at an affordable cost.
And second that as soon as we make changes, we can upset our relative stability and have difficulty re-establishing that.
Oh how right you are Helvella. I would so much more prefer my once Healthy G-D given Thyroids. I would not have to gone through loops to get my Thyroid Hormones that I so much needed. And yes my once healthy Thyroids did make both T3 and T4. Why should it be different to replace both after my TT? I understand some do very well with T4 sole because their bodies can convert T4 to T3 the much needed thyroid hormone. Thank you for this post. Very valuable.
So if I’m reading this correctly, the only possible option for anyone who hasn’t tried combination therapy is ‘no preference’. This gives the impression that those people have tried both and genuinely don’t have a preference, as opposed to they really don’t know whether they have a preference or not.
No - I think the paper is referring only to people who have tried a combination.
The "no preference" group is those who have tried a combination (which could have been LT4+LT3 or desiccated thyroid) and ended up with no preference expressed.
But, even then, if they tried LT4+LT3 then they might find they prefer desiccated thyroid. Or a difference dosing of LT4+LT3.
The studies on preferences have tended to use one approach only - and compare one specific combination against LT4 only. Some have adjusted doses - e.g. to maintain TSH or whatever. But I don't think any of them have actively pursued the optimum dose for the individual based on how the patient feels and blood tests. Not have they continued for years.
Excluding four studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97, 95% CI: 1.52 to 2.54; p < 0.00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84, 95% CI: 1.50 to 5.39; p < 0.00001). Network meta-analysis confirmed the preference for DTE and L-T3+L-T4 versus L-T4 alone.
That text above comes from the Results section of the abstract. What it suggests to me is that the researchers were hoping to find a subset of results in which there was no preference, and if they'd found such a subset that is what their paper would have been based on.
Whereas my view is that is you actually tried enough combinations, you'd almost certainly find few preferred straight LT4.
(And everyone ignores that LT4 tablets are allowed up to 1% LT3 as impurity/degradation product. Though few actual tablets are likely to reach that limit.)
I thought that Bianco's latest book actually acknowledged that some people need T3 as well as T4. But then I haven't read it so I could have got the wrong end of the stick.
I have only read excerpts and other sources. However I think I commend him in this instance for ‘getting around’ and frankly handling quite a lot of flack from the rank of the ‘fuddy duddies’. His pace which might not quite suit us appears to be having an effect on the ‘fuddy duddies’ though it might be imperceptible and it could all be in my imagination!
Levothyroxine (LT4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of the LT4 treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (LT3) or with desiccated thyroid extract (DTE).
Then concludes that 52% of patients prefer LT4 +LT3. Not exactly a minority!
The authors are Brazilian, I don't know what their version of Good Medical Practice says but the UK GMP says that a the patients wishes have to be taken in to account when agreeing on therapy.
I'm not a fan of meta analysis as these can inherit built in errors in methods and conclusions. but its still useful. Thanks helvella
Meta analyses are deeply questionable and, in general, I hate them. But sometimes - as here - they are simply what we have.
The 52% is of those who have trialled combinations. Selection criteria for these trials is a major factor. Could still be a minority of all who take levothyroxine.
Two of the authors are in the USA so I'd expect differences to USA standard would be mentioned.
Interesting i did read a Denmark study last month but never saved it. For once they tested people with no thyroid issues. All of the TSH were higher than 1 apart from two persons
Also the FT3 to FT4 was much a higher percentage too. I wonder why nobody has bothered to test people with normal levels. I expect they have but I had never read it before.
I'm uneasy about this. I was doing fine with just LT4, but a doctor-in-training at the local clinic was all on fire to add LT3 to my treatment. I felt worse, but it took years of struggle to get the LT3 taken out of my regimen. There are many causes of problems remaining after starting to receive LT4, but I suspect that most, by far, are due to something else.
Because LT4 is converted to LT3 mostly in the liver and kidneys, it would make sense to see if there are problems there if a patient really needs the LT3 to feel better.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
