No, T4 does not always convert to enough T3.

we do not convert all our t4 into t3“T4 is converted into T3 at the cellular level in virtually all organs”

This is what Canada’s endocrinologists claim at the opening of their statement under their recommendation “Don’t use Free T4 or T3 to screen for hypothyroidism or to monitor and adjust levothyroxine (T4) dose in patients with known primary hypothyroidism.”

What does this statement so obviously omit? Disorders in thyroid hormone conversion.

No, the human body does not merely convert T4 into T3.

Such a simplistic statement hides the truth that during T4 monotherapy, many patients experience lower T4 conversion to T3, and more T4 conversion into “Reverse T3” instead.

REVERSE T3

Conversion to Reverse T3 is not just a phenomenon that happens in illness.  If you look at the teachings of thyroid biology, illness is simply not the only cause and trigger of thyroid hormone inactivation and excess Reverse T3.

The enzymes that create Reverse T3 are active in almost every tissue in our body, ready to spring to action whenever the slightest excess of T4 or T3 creates a need for thyroid hormone inactivation.

In the ill patient with a normal thyroid, T4 conversion to Reverse T3 happens because the body wants to lower the metabolism by diverting production of T3 to RT3 instead.

In the T4-treated thyroid patient, chronic excess RT3 happens because you continually resupply them with the same level of T4 hormone every day, which they might have difficulty converting into T3.

If T4 is even slightly higher than the body’s set point, every day a lot of T4 gets inactivated to Reverse T3, and every day this cycle repeats when you ingest more T4.

We don’t measure T2 outside of research, but the same enzyme that makes T4 into RT3 also steals our T3 by turning it into T2 at the same time. That’s why it leads to T3 depletion. (2)

OUR PERSONAL T4 TIPPING POINT

Even beyond bloodstream where T4 and T3 cannot be measured, thyroid scientists know that a mild excess of T4 that goes past a tipping point can drastically reduce T4-T3 conversion and enhance conversion to Reverse T3 instead, especially in the brain. (2, 3)

This may be why so many treated thyroid patients experience hypothyroid symptoms as cognitive decline and mood disturbances despite TSH being in normal range, if Free T4 is too high and T3 is too low — despite both hormones being within the statistical population reference range.

In other words, if you go past the tipping point, which is different for each individual and may be located in the upper-normal FT4 reference range, you can lose a lot of T4 into a bottomless pit of RT3 … and your FT3 can actually drop after an increased T4 dose.

THE FT3:T4 RATIO

But you don’t need to test Reverse T3 to see this happening.

The effects of excess conversion to Reverse T3 can usually be seen in a low fT3:T4 ratio in blood in a patient treated on standard T4 monotherapy.

In general, thyroid patients’ fT3:T4 ratio is significantly lower than normal people with healthy thyroid glands. (4, 5)

Specifically, the fT3:T4 ratio in healthy patients with normal thyroid glands is usually maintained in a tight range around 0.31 to 0.33 pmol/L, but in T4-treated patients the average is 0.23 to 0.24 pmol/L. (5)

What these averages obscure is the narrow control of FT3 levels in healthy patients and the wide variation in FT3:FT4 between individuals on thyroid therapy.

Thyroid patients can suffer an incredibly low T3 below reference range.

In fact, some Canadian thyroid patients whom we know personally have suffered a ratio as low as 0.14, with a high Reverse T3 at the same time, over the long term.

What makes the fT3:T4 ratio drop so low in some treated thyroid patients? Two factors:

1) a person’s lack of thyroid tissue, and

2) some individuals are less able to convert T4 into T3. (4)

Now that we know how different treated patients are from healthy patients, let’s return to the Endocrinology association’s further dismissal of Free T3 and Free T4 measurement in patients treated with levothyroxine.

3 MORE PROBLEMS IN THEIR NEXT CLAIM …

See part 2: The pituitary response is abnormal. Stop TSH worship.

REFERENCES

IMAGE: Chatzitomaris, A., Hoermann, R., Midgley, J. E., Hering, S., Urban, A., Dietrich, B., … Dietrich, J. W. (2017). Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00163

(1) #3 in Endocrinology and Metabolism: https://choosingwiselycanada.org/endocrinology-and-metabolism/

(2) Gereben, B., Zeöld, A., Dentice, M., Salvatore, D., & Bianco, A. C. (2008). Activation and inactivation of thyroid hormone by deiodinases: local action with general consequences. Cellular and Molecular Life Sciences: CMLS, 65(4), 570–590. https://doi.org/10.1007/s00018-007-7396-0

(3) Werneck de Castro, J. P., Fonseca, T. L., Ueta, C. B., & McAninch, E. A. (2015). Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine. Journal of Clinical Investigation, 125(2), 769–781. https://doi.org/10.1172/JCI77588

(4) Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015). Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. Endocrine Connections, 4(4), 196–205. https://doi.org/10.1530/EC-15-0056

(5) Gullo, D., Latina, A., Frasca, F., Le Moli, R., Pellegriti, G., & Vigneri, R. (2011). Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients. PLoS ONE, 6(8). https://doi.org/10.1371/journal.pone.0022552



Categories: Deiodinases, Free T3 test, Free T4 test, FT3:FT4 ratio

6 replies

  1. Any ideas on how to correct this? I have this current problem. Lower T4 and add T3?

    • The traditional solution, which was the standard used before TSH became the target of therapy, is to raise the T4 dose if you can handle it, and if your doctor permits the TSH to fall low. Once the T3 rises past about midpoint of reference it starts to enhance Deiodinase type 1, and conversion rates can be boosted so much that some people can get to the top of reference range for free T3.

      The other more obvious solution, which does not require your body to carry a heavy T4 load, is to dose T3 and lower your intake of T4 until you optimize a FT3:FT4 ratio within the reference range that obtains symptom relief.

      • I am really trying to figure this out. I am a vet, even wrote my major in hypothyroidism and still I do not se the big picture and I am not well regulated, as my weight is going up and up… A very active woman age 49.

        So I get 100 mg t4 and 10 mg t3 twice daily, my FT3 : FT4 is 0.36 which is higher than “normal”.
        Does this mean I should lower my T3 to stop my body from producing rT3?
        I can NOT loose weight even if I stay at 1400 kcal daily AND exercise. Nothing happens… and I am category overweight now.

      • Hi Stina. Sorry to hear of your weight struggles. Weight loss while being on thyroid therapy is a big challenge for many people. There are a lot of nutritional factors that synergize with thyroid hormones, and different ones can get in the way or help. Our bodies are so individual.

        I recommend learning from thyroid patient support groups to find out what worked for others. Low-carb high-fat worked for my weight loss years before my thyroid hormones were optimized (I followed Dr. Eenfeldt at the Diet doctor website).

        The RT3 hormone is a byproduct of T4. It can’t be made from T3 hormone at all. T3 converts into two types of T2 hormone, and T2 converts to T1, then T1 into T0 (T-zero). This process only goes in one direction, as each hormone loses 1 iodine atom at a time.

        In science, a high RT3 level is not known to be a barrier to weight loss. In fact, people who have severe Graves’ hyperthyroidism have higher RT3 levels than anyone else, but they tend to lose too much weight because excess T3 is getting into receptors in spite of their high RT3. (See our post on RT3 levels in health and illness.) Also, RT3 tends to rise high in long-term calorie restriction.

        However, if either T3 or T4, or both, rises higher than your healthy levels, it can trigger the Deiodinase type 3 (D3) enzyme that converts T4 to RT3 and converts T3 to T2. This D3 enzyme normally does us a favor by defending our cells from being flooded with a mild excess thyroid hormones, but it can’t prevent thyrotoxicosis in overdose or hyperthyroidism.

        RT3 is the signal of a pathology in one special circumstance: When RT3:FT4 ratio rises and the FT3:FT4 ratio falls, it is usually a result of a severe nonthyroidal illness disturbing our metabolism of thyroid hormones. If your FT3:FT4 ratio was low before you became ill, you can lose even more T3 and could be at higher risk. I do not think you are likely to be in danger of that given your dose ratio and blood ratio.

        Given your ratio in blood, it’s good that you are not in a T3 deficit per unit of T4. Your ratio in blood is higher than usual because you’re dosing T3. That might be just fine for a person with little to no thyroid function. The ratios in blood can only be compared to averages found in research studies in patients who are dosing the same ratio of T4 to T3 as you are. The dose ratio you take in will influence the bloodstream hormone ratio. But the ratio is not the only thing that matters. Keep in mind the same FT3:FT4 ratio in blood can cause hypo if it is anchored in a low FT4 and cause hyper if it is anchored in a higher FT4.

        Your dosing ratio of 100 mcg LT4 and 20 mcg LT3 per day works out to 5 to 1 mcg of T4 to T3. This was a very successful dosing ratio in the LT4-LT3 combination therapy study by Appelhof in 2005, so apparently they did not underdose or overdose them in this research study: https://pubmed.ncbi.nlm.nih.gov/15705921/

Trackbacks

  1. The pituitary response is abnormal. Stop TSH worship. – Canadian Thyroid Patients Campaign
  2. Our wish: May you be blessed with T3 sufficiency – Thyroid Patients Canada

Leave a public reply here, on our website.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: