Paradigm shifts in thyroid hormone replacement ... - Thyroid UK

Thyroid UK

111,471 members129,631 posts

Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism


Wilmar M. Wiersinga

Nature Reviews Endocrinology (2014) doi:10.1038/nrendo.2013.258 Published online 14 January 2014




Author information

Impaired psychological well-being, depression or anxiety are observed in 5–10% of hypothyroid patients receiving levothyroxine, despite normal TSH levels. Such complaints might hypothetically be related to increased free T4 and decreased free T3 serum concentrations, which result in the abnormally low free T4:free T3 ratios observed in 30% of patients on levothyroxine. Evidence is mounting that levothyroxine monotherapy cannot assure a euthyroid state in all tissues simultaneously, and that normal serum TSH levels in patients receiving levothyroxine reflect pituitary euthyroidism alone. Levothyroxine plus liothyronine combination therapy is gaining in popularity; although the evidence suggests it is generally not superior to levothyroxine monotherapy, in some of the 14 published trials this combination was definitely preferred by patients and associated with improved metabolic profiles. Disappointing results with combination therapy could be related to use of inappropriate levothyroxine and liothyronine doses, resulting in abnormal serum free T4:free T3 ratios. Alternatively, its potential benefit might be confined to patients with specific genetic polymorphisms in thyroid hormone transporters and deiodinases that affect the intracellular levels of T3 available for binding to T3 receptors. Levothyroxine monotherapy remains the standard treatment for hypothyroidism. However, in selected patients, new guidelines suggest that experimental combination therapy might be considered.

Yes please, more tests :-)

7 Replies

shambles, nice find, wish it wasn't behind the pay wall. You might enjoy this editorial by Dr. Wiersinga. PR and this study

helvellaAdministrator in reply to PR4NOW

Sadly, the end of the first of your links says this:

Six years ago, three editorialists had an impossible dream: thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients (35). Hopefully, their dream will come true in the next 6 years.

That was in 2009 - only two years left and no sign of a significant change... :-(

Still, patient power might be the biggest factor within the next few years.

PR4NOW in reply to helvella

Rod, I am actually somewhat optimistic about the future, we will reach a tipping point. I am seeing positive changes in the US. Granted that we are an unruly mob over here but that does have some advantages. All the MD's that have gone into Holistic, Integrative, Functional, CAM and Anti-Aging medicine are much more likely to treat the patient and their symptoms first instead of the lab test. And I am continually amazed at how patient friendly ND's are, especially in regards to the thyroid arena. We just need to get more graduated and get more states where they can be licensed to be primary care doctors and write scripts. Apparently, there are some people at work on a Thyroid Summit which if it is handled right could be a very positive event. Because the UK is smaller and more tightly controlled (GMC) I think it will be a tougher battle there, but if we keep pushing everywhere we will get there. After all, 13,000 members at TUK HU, who would have thought it would grow that much. I think you are right, it will be patient power that will eventually force the change. PR

helvellaAdministrator in reply to PR4NOW

Optimistic, yes, I am about some future. :-)

But pessimistic I am about the time-scales. :-(

One of the very useful features of this forum is that, though it is strongly UK-focussed (with a fair Irish contingent!) - the members from the rest of the world add perspectives that simply would not be appreciated without them.

At last! This is a very important study for those stuck on T4. But beware 'experimentation' especially by Endo or gp! Can make you very poorly.


Thanks for posting this. :-)

The author's details (at the bottom of the page on Nature's site) are given as:

Author details

Dr Wilmar M. Wiersinga is Professor of Endocrinology at the University of Amsterdam, Netherlands, and was Chief of the Division of Endocrinology & Metabolism at the Academic Medical Centre in Amsterdam during 1996 2007. His main research topics are autoimmune thyroid disease (especially Graves ophthalmopathy), nonthyroidal illness syndrome, and amiodarone. In the past he has served as President of the European Thyroid Association, and currently he is editor-in-chief of the European Thyroid Journal.

Which rather suggests that he is in an influential position and has the respect of at least a reasonable number of other thyroid people. That is, I think, a good thing and gives this more chance of being at least read by others.

shambles in reply to helvella

Thanks Rod. I hope it gets read and brings further investigation, study or interest. Even if there could be some universal recognition that some people are not able to convert as effectively as others would be a start.

You may also like...