The Study
Human Type 1 Iodothyronine Deiodinase (DIO1) Mutations Cause Abnormal Thyroid Hormone Metabolism
This study found two families with weird thyroid test results and discovered they had rare changes in a specific gene. It shows that these gene changes are linked to the weird results, but it doesn't prove the gene changes cause the problem in everyone—it's just seen in these two families.
Analysis score
Maximum 58 for a case-control study.
Where the score came from
Two rare gene changes stop the body from turning thyroid hormone into its active form properly, causing a backup of an inactive version.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 549 / 100
Quality score
Researchers compare people who have a condition (cases) with similar people who do not (controls), looking back in time for differences in exposure. Useful but more prone to bias.
Key takeaways
Summary
Based on the study abstract and findings.
- 1Yes — this means the body can't use thyroid hormone efficiently, which could cause fatigue or other thyroid-related symptoms even if standard tests look normal.
- 2The gene changes made the enzyme 2–3 times worse at grabbing its target hormone, leading to higher levels of inactive rT3 and higher rT3/T3 ratios.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
Thyroid
Year
2020
Authors
M. França, A. German, G. W. Fernandes, Xiao-Hui Liao, A. Bianco, S. Refetoff, A. Dumitrescu
Related Content
Claims (10)
Thyroxine (T4) must be converted into triiodothyronine (T3) to become biologically active, and this conversion requires two specific enzymes called deiodinase type 1 and type 2. Changes in the genes that produce these enzymes can reduce the body's ability to activate thyroid hormone.
The body converts the thyroid hormone T4 into its active form T3 using enzymes that require selenium. Changes in the genes that code for these enzymes result in lower T3 production.
Mice with one defective copy of the DIO1 gene show higher levels of reverse T3 and a higher reverse T3 to T3 ratio in their blood, just like humans with the same genetic condition.
When one copy of the DIO1 gene is not functional in humans and mice, serum levels of reverse triiodothyronine (rT3) rise and the ratio of rT3 to T3 increases, demonstrating that having only one working copy of the gene is sufficient to alter thyroid hormone metabolism.
Two specific genetic changes in the DIO1 enzyme reduce its binding to thyroxine, leading to a two- to threefold higher Michaelis constant and reduced reaction speed in laboratory cell studies.
Mice with one nonfunctional copy of the Dio1 gene have higher levels of reverse T3 and a higher reverse T3 to T3 ratio in their blood, matching the biochemical pattern seen in humans with specific DIO1 gene variants.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.