Thyroid UK
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T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy

T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy

Another paper asking deep questions about adding T3. It particularly mentions and discusses bone issues. Well worth a read if you are interested. Much of the paper is easier to read than the Abstract below! And free, open access to full paper.

Perhaps surprisingly, they equated 20 mcg of Liothyronine to 50 mcg levothyroxine.

Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study


Background: A recent randomized controlled trial suggests that hypothyroid subjects may

find levothyroxine (L-T4) and levotriiodothyronine combination therapy to be superior to

L-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.

Hypothesis: Peripheral tissue might also be stimulated during T4/T3 combination therapy

compared with T4 monotherapy.

Methods: Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal

peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing

hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in

26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the

replacement therapy with T4/T3 in combination (50 mg T4 was substituted with 20 mg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.

Results: TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3

combination and T4 monotherapy respectively; PZ0.534). SHBG increased from (median)

75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (PZ0.015) but remained unaltered in

the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (PZ0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 mg/l (P!0.001)). NT-proBNP did not differ between the groups.

Conclusions: T4/T3 combination therapy in hypothyroidism seems to have more metabolic

effects than the T4 monotherapy.


13 Replies

Very interesting! Thanks for posting it. More help for those still unable to convince their doctors :) It's good to see the research is being done!


Try this link:


You will see the thyroid research papers recently published (I think you should see something like 'last 24 hours'). Yesterday there were 24 papers. If that happens every day (and it is not very far off that), we might see 8760 new papers a year.

But how much of this huge volume of research ever gets out to patients?

Precious little. We have seen some movement towards "allowing" bed-time dosing. And a flurry of doses being cut as a knee-jerk reaction because of fear of bone and/or heart issues. And I am then struggling...


It won't let me view them. I get an error. Maybe because I am not registered? I will try and register and see what happens, but I think I tried registering before but it wouldn't let me. Hmmm...


It should work if you go here:

And then copy and paste this entire text below into the Search box:

(((thyroid) AND "2013/02/15 15.00"[MHDA]:"2013/02/16 15.00"[MHDA])) NOT (( ((("thyroid gland"[TIAB] OR ("thyroid"[TIAB] AND "gland"[TIAB]) OR "thyroid gland"[TIAB] OR "thyroid"[TIAB] OR "thyroid (usp)"[TIAB] OR ("thyroid"[TIAB] AND "(usp)"[TIAB]) OR "thyroid (usp)"[TIAB]))) AND "0001"[EDAT]:"2013/02/15 15.00"[EDAT]))

That says, show me short summaries of all papers published between 15:00 on 15/02/2013 and 15:00 16/02/2013.

Have no idea why you would be having difficulty in signing up - I did so many years ago and never seem to have an issue with getting connected/logged in. But that also means it is difficult for me to be sure what happens if you are not signed up!


Thanks. That worked fine :) There are a lot of papers but so many of them are not accessibly without parting with cash :( I have viewed a couple that were interesting though.


So, so true.

If you go to PubMed Central, you can see papers that they hold (a huge number of more historic papers).

And it does seem to be that more papers are being published on Open Access sites such as Hindawi and PLOS One.


I shall have a look at those too. Thanks :)


Rod, University of Nebraska Medical Center, here in Omaha, is one of the institutions listed on the PLOS One website. Didn't know that, thanks for the link. Haven't seen much from them related to endocrinology though, the midwest is pretty conservative, standard thyroid stuff. PR

PS Thanks for the other link too, interesting.


I am due to visit an endo soon and am gathering all info I can for the appointment. What I've noticed is that there's very little material on thyroid coming out of the UK. It just doesn't appear to be an area of research interest. Any thoughts on this?


Seems that we get a lot of papers from around the world - but it is difficult to assess the amount of research from paper-count alone.

We certainly are seeing papers from USA, China, Brazil, Korea, Japan, Italy, Spain, Germany, Serbia, Iran, Russia, Saudi Arabia, Netherlands, Poland, India, Uganda, Austria, Taiwan, Eire, Sweden, and others. The constituent countries of the United Kingdom are all represented! So much work is now in some form of team that it is very easy to mis-apprehend who did what without going into lots of detail.

It also sometimes appears that some countries not usually recognised as hot-spots of thyroid research might be pushing out some papers for prestige rather than real, novel value. Not that this is a bad thing - it is important that they are taking part.


Thank you so much for posting this. Next month I have an endo appointment and the new GP. I've been a bit worried about being on t4 only due to the issue of long term side effects and maybe its worth a discussion with the endo and gp since i still have symptoms on the mono therapy.


I hope it helps. :-)


Thanks for posting, I'm printing it out now to take to my GP next visit. I'm nearly at the point of asking for combo therapy, I pretty much know what the answer will be but will go there nevertheless. Roll on the next bunch of papers!


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