Thyroid UK
84,030 members99,015 posts

Neither Baseline nor Changes in Serum T3 during T4/T3 Combo Therapy Predict Positive Response in Hypo Patients with Persistent Symptoms

There is grossly inadequate detail to understand what they actually did!

The number in the trial is far too small.

The use of a 17:1 ratio is very likely inadequate - and the rationale for using that ratio is questionable.

It looks as if 65% responded (I assume that means had improvement of symptoms?) and yet the whole abstract is so deeply and drearily negative, it actually feels as if it was reporting 65% got worse!

Obviously, this paper will become a classic one for similarly negative medics to refer to.

Possibly, there is just an outside chance that when the full paper becomes feely available in October, it could make a bit more sense?

Eur Thyroid J. 2017 Apr;6(2):89-93. doi: 10.1159/000454878. Epub 2017 Jan 19.

Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms.

Medici BB1, la Cour JL1, Michaelsson LF1, Faber JO1, Nygaard B1.

Author information

1 Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.



Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients.


To evaluate whether measuring serum triiodothyronine (S-T3) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T4/L-T3 combination therapy.


Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T4 therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T4/L-T3 combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders.


Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T3 and in free T3 estimates. Further, logistic regression showed no correlation between S-T3 and free T3 estimates and responder/nonresponder status.


Our data indicate that serum T3 measurements are not suitable to predict which patient will benefit from L-T4/L-T3 combination therapy, and treatment response cannot be followed by repeated T3 measurements either.


Levothyroxine; Liothyronine; Serum triiodothyronine

PMID: 28589090

PMCID: PMC5422753 [Available on 2017-10-01]

DOI: 10.1159/000454878

14 Replies

Bit of a case of 'spot the free T3 test', it doesn't appear in the research question, conclusion, or definition of euthyroid, but is in the results.


I'm not so sure it does seem that negative, just seems to stating that you can't determine those that will benefit from combination therapy from their T3 blood test results beforehand or after but still suggest that some responded positively to it.

Do need to read the whole thing though.

At the end of the day, this is the first research paper that I've come across that actually based their findings on what the patient reported in regards to how they felt/responded rather than blood tests lol - maybe just because I haven't read enough of them?


It does imply the majority reported benefits from combination therapy though :-)

1 like

It does - the statements are not so negative, but the way it is worded makes it so sound negative.


Yea. It's strange that it acknowledges T4 doesn't work well for everyone, takes seriously patient symptom reports, but doesn't see it as a good thing that 65% get improvement.

1 like

I wonder if it's negative because the finding is that blood tests aren't predictive or descriptive. And as blood tests are the only important thing, this means nothing of interest was found.

1 like

It is written badly which isn't helping. I suppose the problem is, we're reading it from a negative perspective due to having issues with T3 treatment in the UK. This was from Denmark and they might not be considering it from this point of view as don't think rest of the world are so anti-T3 so prob not thinking about how it could be taken and probably not intentionally written that way?

Maybe they were just annoyed/deflated that they didn't get the results they were hoping for making it a little bit of a wasted effort lol :-)

1 like

Yeah I see it more about is testing ft3 consistent with how one feels as one with relatively low ft3 can feel healthy and normal compared to one in midrange who can feel ill.


The outcome of the study is that (because they were TSH/T4 Euthyroid before testing) - no form of Thyroid testing successfully indicated treatment outcomes.

Unfortunately they did not say that either because it did not meet their aims to do so, or assumed busy doctors would assume that from the patient selection criteria. The likely effect is to re-enforce both the refusal to supply T3 and the Refusal to test.


There is a problem here that the authors did not consider. If too much T4 is given to patients who cannot properly convert it, then regardless of any additional small amount of T3 offered, the excess T4 actually inhibits body T4-T3 conversion and rT3 is made instead. Thus the combination of reduced T3 coming from T4 excess combined with the extra T3 given makes for a mixed picture and I'm not surprised about the indeterminate outcome. The trial should have been done with much less T4 to allow the effect of added T3 to show through more clearly, without the negative impact of inhibition of conversion..


All this seems to be saying is that blood tests don't show/ predict which people will benefit from combined T4/T3. It doesn't say whether those people had improved symptoms -----or not ----as far as I can see.


Full text available on request from authors on Researchgate:

1 like

Afraid I have not had much luck with Researchgate requests. They seem to come back for email verification then nothing.


Anyone interested in reading the whole paper can see it here :

Note that papers sometimes disappear from sci-hub so take a copy if you want to be able to access it later.

I haven't read it myself, sorry - I'm far too tired!


You may also like...