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Most people have never heard of reverse T3 and, unless they work in critical care, most doctors haven’t heard of it either. This is because it is rarely tested for in the normal population. Reverse T3 is beginning to make waves in alternative and functional medicine, but is there any real evidence to suggest it might have a role to play in the management of people with thyroid conditions?
The most plentiful thyroid hormone produced by the thyroid gland is T4 (thyroxine) – so called because it has 4 atoms of iodine in its structure. T4 is not a potent thyroid hormone – to affect the body’s metabolism it must convert to T3 (tri-iodothyronine) which has a more pronounced effect on the body’s tissues. It does this by the removal of an atom of iodine - hence T3. Reverse T3 (rT3) is also made by the same process but in this instance a different atom of iodine is removed. This creates not only an inactive version of T3, but one which can compete with T3 for the receptors on our cells[i],[ii].
T4 normally converts to both T3 and rT3 (but more T3 than rT3) so it is completely normal to have some rT3 in our blood. However, there are some circumstances when the body starts to convert more T4 to rT3 instead of T3, inhibiting the amount of T3 available to our cells.
Why would the body do this? It is thought that it does it in response to acute injury and stress in order to preserve energy and focus on fixing the problem. Most of the studies into rT3 to-date have been on patients admitted to intensive care where the phenomenon of low T3 but elevated rT3 was first noted[iii],[iv]. It can also be found in people on restricted calorie diets and people with liver disease, pulmonary disease, diabetes and heart failure[v].
Testing for rT3 can provide insights for people who are taking thyroid medication but are not feeling better. To get a good picture of what is going on with your thyroid function, we test your TSH and T4 levels, as well as FT3, rT3 and the ratio of FT3 to rT3. A low ratio can indicate that your body is trying to conserve energy to fix a problem; what it won’t tell you is what that problem is. If you are known to have another health condition then it can be a sign that your control of this needs to be improved. Even if you are otherwise well it can be reassuring to know that the symptoms which may have plagued you for years are not all in your head. It is of limited use in guiding the treatment of a thyroid condition because as yet, there has not been a great deal of research into the use of rT3 outside of an intensive care unit.
[i] Zevenbergen, C., Meima, M.E., Lima de Souza, E.C., Peeters, R.P., Kinne, A., Krause, G., Visser, W.E. & Vis- ser, T.J. 2015. Transport of iodothyronines by human L-type amino acid transporters. Endocrinology 156, 4345–4355.
[ii] Kinne, A., Kleinau, G., Hoefig, C.S., Gruters, A., Kohrle, J., Krause, G. & Schweizer, U. 2010. Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8. J Biol Chem 285, 28054–28063.
[iii] Tognini, S., Marchini, F., Dardano, A., Polini, A., Ferdeghini, M., Castiglioni, M., & Monzani, F. (2009). Non-thyroidal illness syndrome and short-term survival in a hospitalised older population. Age and Ageing, 39(1), 46–50. https://doi.org/10.1093/ageing/afp197
[iv] Golombek S.
Nonthyroidal illness syndrome and euthyroid sick syndrome in intensive care patients.
Semin Perinatol (2008) 32:413–8.
[v] Moura Neto, A., & Zantut-Wittmann, D. E. (2016).
Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings.
International Journal of Endocrinology, 2016.