Positive Health Online

Thyroid disorders affect one in twenty in the UK although this number is underestimated as many go undiagnosed.  Proper functioning, metabolism and protection of the thyroid is largely dependent on selenoproteins. 

Overview of the thyroid system. Courtesy of Wikipedia
https://en.wikipedia.org/wiki/File:Thyroid_system.svg

Enzymatic reactions that catalyse the conversion of thyroid hormones are triggered by Se-dependent selenoprotein enzymes called iodothyronine deiodinases type 1 (D1), type 2 (D2) and type 3 (D3). These deiodinases are responsible for the regulation and bioactivity of thyroid hormones, the conversion of T4 to T3, T4 to reverse T3 (rT3), T3 to T2, and the degradation of thyroid hormones.

For many patients, myself included, when there is dysfunction in thyroid production this can lead to a need for not only thyroxine (T4) but also triiodothyronine (T3). Early studies show that some patients have a certain gene, DIO2 variant rs225014, also known as THr92Ala 5’, on chromosome 14, that predispose them to slow conversion of thyroid hormones. 

Another mechanism that has been shown in animal models is that deiodinase type 2 is down-regulated in the presence of T4 with a 20-minute half-life. If less T4 is present D2’s half-life is much longer and therefore up-regulated to convert more T4 to T3. This could explain why rats on T4-therapy saw a reduced conversion to T3 at 20% compared to combination treated rats at 25%. These results indicate that mono T4 therapy reduces whole body D2-dependent T4 conversion to T3. If this is the case for humans then prescribing higher doses of T4, when thyroid symptoms persist, could worsen the situation.

The testing of free T3 is unusual with your GP, and sometimes even an endocrinologist, maybe because the treatment with Levothyroxine is one of few medications available on prescription. Rarely was T3 prescribed unless the patient insisted and proved a need.

This situation worsened in November 2017 when T3 medication was withdrawn and became unavailable on prescription from the NHS. This has resulted in patients seeking private healthcare, if they can afford to do so, costing hundreds of pounds plus the cost of the medication each month.

Thyroid UK completed a patient experience survey in 2015 which clearly displays the inadequate care for people with thyroid disorders. In the report, the cost of seeking a private doctor is high with 17% spending more than £500, 13% more than £1000 and 10% more than £2000. I know I spent over £2000 in 4 years to see a private doctor, pay for tests and buy my medication.

What’s very odd is that affordable versions of T3 medication are readily available in some European countries for much less than the NHS were paying. My pharmacist informed me that it was costing the NHS £258 per month per patient for T3 and yet from countries like Germany it is available for as little as £9 per month. 

I suffered from typical low thyroid symptoms such as depression, low energy, fatigue and anxiety for years after being diagnosed at the age of 10 with hypothyroidism and put on Levothyroxine.

During my studies to become a Nutritional Therapist in my mid-20s and specializing in thyroid care for my Masters, I sought the help of a private doctor who prescribed Armour Thyroid (a desiccated thyroid extract that combines T4 and T3 hormones). I was turned down by the NHS for T3. Within a short time, I started to feel better. My depression lifted, I stopped sleeping as much (it was normal for me to sleep most of the weekend), I had more motivation for life and I was happier. It has totally changed my life. For years I was suffering with low T3 and this was not picked up. The new medication combined with nutritional and lifestyle changes has continued to improve my health.

There is an assumption that the conversion of T4 to T3 is taking place in the peripheral tissues and providing adequate T3. There is also a question of whether the T3 is being effectively transported across the cellular membrane into the cells of peripheral tissues. As the transport of thyroid hormones into the cell is energy dependent, this could be reduced in patients with thyroid disease and many other common diseases that impact mitochondria.

Another issue for women, who are not aware of a lack of conversion, is conceiving a baby when they have inadequate thyroid hormones which can cause problems for the growing foetus. Thyroid hormones are particularly important during the first twelve weeks of gestation to ensure the baby has healthy brain function and to prevent mental disabilities. There is also an increased need for thyroid hormones throughout pregnancy. I was advised that I should be regularly tested and to increase my medication including my T3 if I conceived.

The potential long-term costs of having thousands of patients suffering from thyroid symptoms will likely cost the NHS much more in the long run. For example, infertility, chronic fatigue, heart conditions, high cholesterol, anaemia, hormone, gallbladder and liver issues can all result as further complications from long-term untreated thyroid conditions.

Thyroid care certainly needs to move forward and NHS endocrinologists should be able to advance their care with the necessary medications, testing and nutrition and lifestyle guidance, all of which can transform a patient’s life. Certainly removing T3 prescriptions is a backward step and incredibly worrying for people with thyroid disease who rely on this hormone.

Quote from Thyroid UK:
“Thyroid UK is hearing from hundreds of patients who are either afraid that their T3 is going to be withdrawn from them or who are now feeling ill again because it has already been withdrawn prior to the NHS England consultation.   We hope that NHS England will listen to thyroid patients and learn from more recent research than that in the current guidance for primary hypothyroidism.  Many patients who do not respond well to levothyroxine do not have primary hypothyroidism and yet there is no guidance relevant to their condition. We have asked for a meeting with Matt Hancock (who replaces Jeremy Hunt) to discuss this.”

Clinical Research Study
Panicker, V., Saravanan, P., Vaidya, B., Evans, J., Hattersley, A.T., Frayling, T.M., Dayan, C.M., 2009. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. Journal of Clinical Endocrinology and Metabolism, 94(5), p.1623-1629.

Notes Regarding DIO2 Gene Variant

• DIO2 gene variant, which is present in approximately 16% of the population, reduces deiodinase activity which slows conversion of T4 to T3, (Butler, et al. 2010).
• Patients with DIO2 gene variant rs225014 seem to respond better to T3/T4 combination hormone replacement.

The initial research surrounding the DIO2 gene variant rs225014 indicates that these patients could benefit from a combination hormone replacement, but the minority numbers with this genetic variant have not presented with significant results thus far. Accurately measuring how a patient feels is also challenging in the field of science that favours quantitative data that can be transferred into useable statistics, over qualitative data that may provide a feeling, thought or emotion. There is a need for double blind placebo controlled studies on subjects who have the DIO2 genetic variant to understand if there is an improvement in health outcomes and a preference for combination hormone replacement.

Research Studies on Single T4 Medication Compared with Combination T3/T4 Medication

Appelhof, B.C., Fliers, E., Wekking, E.M., Schene, A.H., Huyser, J., Tijssen, J.G.P., Endert, E Henk C. P. M. van Weert, E.H.C.P., Wiersinga, W.M. Combined Therapy with Levothyroxine and Liothyronine in Two Ratios, Compared with Levothyroxine Monotherapy in Primary Hypothyroidism: a Double-Blind, Randomized, Controlled Clinical Trial: JCEM, 90(5) p,2666-2674. 2005.

Fadeyev, V.V.,  Morgunova, T.B., Sytch, J.P., Melnichenko, GA. TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine. Hormones, 4(2), p.101-107. 2005.

Fadeyev, V.V., Morgunova, T.B., Melnichenko, G.A., Dedov, I.I. Combined therapy with L-thyroxine and L-triiodothyronine compared to L-thyroxine alone in the treatment of primary hypothyroidism. Hormones, 9(3) p.245-52. 2010.

Nygaard, B., Jensen, E.W., Kvetny, J., Jarløv, A., Faber, J. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology, 161(6), p.895-902. 2009.

Panicker, V., Saravanan, P., Vaidya, B., Evans, J., Hattersley, A.T., Frayling, T.M., Dayan, C.M., Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. Journal of Clinical Endocrinology and Metabolism, 94(5), p.1623-1629. 2009.

Valizadeh, M.,  Seyyed-Majidi, M.R., Hajibeigloo, H. Efficacy of combined levothyroxine and liothyronine as compared with levothyroxine monotherapy in primary hypothyroidism: A randomized controlled trial. Endocrine Research, 34(3), p.80-89. 2009.