Treatment of hypothyroidism with levothyroxine ... - Thyroid UK

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Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study


Far, far too small a group. Why the chosen T4:T3 dosing regime? For some, a halfing of dose from 150 T4 to 75 with the addition of 15 T3. I can't see that being appropriate. (Odd to reduce the dose of some by by 50 and others by 75, don't you think?)

No identification of how they felt before. Quite likely, despite their stable doses, some would have been under-treated and some over-treated.

I don't get this bit at all:

... TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit ...

Not affected followed by the effect! Am I totally mis-reading it?

Arch Endocrinol Metab. 2016 Nov-Dec;60(6):562-572. doi: 10.1590/2359-3997000000192. Epub 2016 Aug 25.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study.

Kaminski J1, Miasaki FY1, Paz-Filho G2, Graf H1, Carvalho GA1.

Author information

1Serviço de Endocrinologia e Metabologia (SEMPR), Departamento de Medicina Interna, Hospital das Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, PR, Brasil.

2Genome Sciences Department, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.



To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism.

Subjects and methods:

This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16.


Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged.


The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

PMID: 27982198

DOI: 10.1590/2359-3997000000192

10 Replies

Well, they do it deliberately. They don't want good out-comes, so they either fix their méthodes to get bad ones, or they lie about the out-comes.

This is a waste of paper. Disregarding the poor treatment regime, the numbers are ridiculously inadequate. Also the subjects are chosen willy-nilly without any regard to their underlying variation in response to thyroid hormones and the basic genetics of their physiology when well. For example if on average there are 10-15% of patients who would benefit from T3, then there will be only 3 or at most 4 out of the 32 that would benefit. But there will be another 3 or 4 out of 32 at the other end of the scale who are sensitive to T3 and that might find T3 too much for them. Statistically therefore you would not see any sensible result. The proper way to do the trial is a) to have a lot - say up to 1000 - of patients. First check their FT4/FT3 ratios on T4 therapy. Second stratify the group into at least 3 subgroups on T4 only with a) low FT4/FT3 ratio, b) middle ratio and c) high ratios. Then compare results on combined therapy versus T4 only in all three groups. Only big studies organized like this will tell you anything. But lumping all in together is futile.

in reply to diogenes

I suspect that this is the sort of "study" that gets half-read, and half-remembered as yet another paper that dismisses combination therapy.

What do we make of the journal that accepted this paper?

in reply to helvella

Very little. Trouble is that there are a lot of useless reviewers out there whose IQ's may be in single figures.. I'm at the moment protesting about the refusal of a journal to publish a letter of ours which refutes a published review which is full of lies factually, and which will say anything however spurious and discredited to get itself published. This journal I won't name, but it is very distinguished. The quality if I can call it that of reveiwing can be absolutely scandalously ignorant.

What a terrible experiment design! It looks like it was designed to fail, but as greygoose says, they do it deliberately.

I've never tried it but I do wonder if it would be possible to send an email to the researchers who do this kind of rubbishy research and give feedback.

I think I would fail in keeping my scorn out of the email though!

in reply to humanbean

Unfortunately for you (but possibly fortunately for them) there is no obvious email contact in the abstract of this paper.


On the full paper (which I have just found) we see this:

Correspondence to: Gisah Amaral de Carvalho. Av. Agostinho Leão Júnior, 285. 80030-110 – Curitiba, PR, Brasil.

in reply to helvella

Ooh - putting me on the spot now. I'll give it some thought. :)


As if an 8 weeks trial would tell you anything.

I should think most on this forum have taken levothyroxine or combined T4/T3 for more than eight weeks and fail to recover fully, even after years sometimes with doctors adjusting doses according to the TSH. Ignoring symptoms.

Are we surprised by this statement:-

No clear clinical benefit of the studied formulation could be observed.

A benefit to whom? They only appear to have discussed blood tests. Where from did they pluck the 75mcg/15mcg doses. Identical for each person. It doesn't make sense to me at all.

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