The T3-4-Hypo trial

A Dutch national randomized placebo-controlled double-blind multicenter trial of LT4/LT3 combination therapy in patients with autoimmune hypothyroidism.


Hypothyroidism is common, affecting 5% of the general population, for which levothyroxine (LT4) monotherapy is the standard treatment. Despite normalized serum thyroid hormone levels, 10-15% of LT4 (levothyroxine) treated patients have various persistent complaints, the most important of which is tiredness. This often leads to a poor quality of life, with withdrawal from society and work. The explanation for the persistent complaints could be that physiological T4/T3 ratios cannot be reached with LT4 monotherapy, as in a healthy individual T3 is not only derived from T4/T3 conversion but is also directly produced by the thyroid itself. Studies have reported contradicting results as to whether addition of liothyronine (LT4/LT3 combination therapy) in patients with persistent tiredness on LT4 monotherapy is effective or not.
This problem is a top prioritized knowledge gap on the national research agenda of the Dutch Society of Internal Medicine (NIV), as endorsed by both the Dutch Endocrine Society (NVE) and the Dutch thyroid disease patient organization SON (Schildklier Organisatie Nederland).

The aim

To investigate whether addition of liothyronine (LT4/LT3 combination therapy) in patients with persistent tiredness on LT4 (levothyroxine) monotherapy is effective or not in relieving tiredness.


Criteria for

Inclusion and exclusion criteria are:

Study design

A Dutch national randomized placebo-controlled double-blind multicenter trial. Six hundred adult patients with autoimmune hypothyroidism will be included who despite biochemical euthyroidism on LT4 (levothyroxine) monotherapy have persistent tiredness with a negative impact on daily life.

Participating centers


: DEXA-scan
 : Neurocognitive test

CenterInvestigatorLocationAdditional tests
Erasmus MCDr. M. MediciRotterdam
RadboudumcDr. R.T. Netea-MaierNijmegen
Rijnstate ZiekenhuisDr. S. RoerinkArnhem 
UMC GroningenDr. W. ZandeeGroningen 
Maastricht UMC+Dr. B. HavekesMaastricht 
UMC UtrechtDrs. S.M. van der LeijUtrecht 
Leids Universitair Medisch CentrumDr. M. SnelLeiden
Amsterdam UMC, locatie AMCDr. E. BruinstroopAmsterdam
CenterInvestigatorLocationAdditional test
Franciscus Vlietland ziekenhuisDr. M.E. KevenaarSchiedam
Maasstad ZiekenhuisDr. C. van NoordRotterdam
Máxima Medisch CentrumDr. P.C.M. Wouters-van PoppelVeldhoven 
Admiraal De Ruyter ZiekenhuisDr. C.K.A. van den BergeGoes 
Albert Schweitzer ZiekenhuisDr. R.M. Kiewiet-KemperDordrecht
Van Weel-Bethesda ZiekenhuisDrs. E. van SchaikDirksland 
Zuyderland Medisch CentrumDr. R. BianchiSittard-Geleen 


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