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Deiodinase 2 (DIO2)

The Deiodinase 2 (DIO2) gene was researched in 2009 and the results were published in a paper titled Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine plus Triiodothyronine Therapy in Hypothyroid Patients.1

Firstly, you need to know that everyone inherits two copies of each gene, one from their mother and one from their father.

To explain this paper briefly, the Deiodinase 2 gene activates triiodothyronine (T3) and the researchers found that a tiny change in this gene could mean that although the body gets enough T3, the brain doesn’t.

The patients on this study were given levothyroxine (T4) only for a set period and then combination treatment of both levothyroxine and liothyronine (synthetic T3). The patients who had normal genes did not feel any different on T4/T3 combination treatment. However, those who had one variant gene (inherited from one of their parents) felt better on the combination treatment and those with two variant genes (inherited from both parents) felt better still.

This means that there is a possibility that patients who are on levothyroxine alone, still have symptoms and have the variant Deiodinase 2 gene may improve with the addition of liothyronine.

Because this gene causes a deficiency of T3 within the cells, the usual thyroid hormone function tests will not show up a problem. This means that your TSH, FT4 and FT3 blood tests will look normal.

The study concluded:

“Our results require replication but suggest that commonly inherited variation in the DIO2 gene is associated both with impaired baseline psychological well-being on T4 and enhanced response to combination T4/T3 therapy, but did not affect serum thyroid hormone levels.”

V Panicker, P Saravanan, B Vaidya, J Evans, A Hattersley, T Frayling & C Dayan

In order to find out if you have the Deiodinase 2 gene variant you need to have the DIO2 genetic test. 

If you have the DIO2 genetic test done and your report shows that you have inherited variants in either one or both genes it may be worth taking your report, along with the research article above, to your GP or endocrinologist and asking for a trial of T3 to be added to your levothyroxine. Remember, all thyroid tests are normal with this variant gene.

Thyroid UK is a member of Genetic Alliance UK, the national charity of over 150 patient organisations which supports all those affected by genetic conditions.

Check out what people are saying on our online community:

Further reading on Deiodinase 2:

New genomic study further explains thyroid treatment problems:
Dr Damien Downing’s Report

Dr Gary Pepper Article:
Breakthrough Discovery: Need For T3 Could Be Genetic

Eurogentest – a project funded by the European Commission:

Recommendations for Genetic Counselling related to Genetic Testing:

Direct-to-consumer genomic testing from the perspective of the health professional: a systematic review of the literature:

Consent and confidentiality in clinical genetic practice:

Genetic Counselling – a Guide for GPs:



  1. Panicker V, Saravanan P, Vaidya B, et al. Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine Plus Triiodothyronine Therapy in Hypothyroid Patients. The Journal of Clinical Endocrinology & Metabolism. Published online May 1, 2009:1623-1629. doi:10.1210/jc.2008-1301


Date updated: 22.02.2024 (V1.5)
Review date:  27.04.22

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