The standard T4 monotherapy results in unnatural distortions in T3:T4 ratios that can lead to chronic T3 concentrations below the healthy mean when TSH is normalized.
But health care systems in Canada do not care how much FT3 you lose compared to other Canadian citizens when you are on T4 monotherapy. They don’t want to know how sick you may get because of it. They are only concerned about the TSH being normalized.
Proof of the lowered T3:T4 ratios in T4 monotherapy has continually shown up in research over the decades. Here are three examples spaced about ten years apart from each other:
- Liewendahl et al, 1987: “There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4.”
- Woeber et al, 2002: “in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.”
- Sesmilo et al, 2011: [A study of L-T4 treated central hypo vs. primary hypo and untreated controls] “Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered.”
Why are questions about clinical significance still unanswered in research when the significance of lower T3 levels is clear in collective patient experience?
First of all, too many medical researchers start with the false presumption that any and all FT3 levels within the reference range are acceptable for health. Reference ranges in thyroid hormones are unlike most others in health care. The healthy range for an individual can be 50% narrower than the range derived statistically from a larger population (Andersen et al, 2002 & 2003).
Secondly, researchers who have studied T4 monotherapy often do not measure FT3 because they either lack the data at a population level because it’s not being routinely collected, or they simply don’t care to measure it.
Thirdly, when they do measure FT3, their statistical analysis methods are not appropriately sensitive to human variation. They too often focus on average FT3 across large cohorts with varying thyroid function and varying T4-T3 conversion efficiency.
The problem with averaging is that the extremes of patients with lower FT3 while on T4-therapy are hidden by having their levels averaged with patients blessed with a higher FT3.
Because of these systemic blinders preventing research on thyroid patients’ suffering, no researchers have ever bothered to examine the long term health effects of a relatively low level of FT3 within or below range.
It is an ethical failure in research. No studies have focused only on the FT3 levels of those patients who suffer. Such patients are simply forced to live a diminished life with this lower FT3 level for decades.
As for clinical significance of FT3 levels, ask patients who have tracked their own health outcomes to their own FT3 data.
When FT3 is reduced relative to a patient’s individual set point, you will lower that patient’s health and quality of life even if their FT4 is raised and TSH is normal.
When patients are permitted to increase their FT3 levels enough for their individual needs, they gain freedom from chronic hypothyroid symptoms and various health problems.
How do you know what a patient’s healthy FT3 level and T3:T4 ratio is if you do not permit them to achieve it?
What if some patients can never achieve optimal FT3 on T4 monotherapy?
How can patients explore what their optimal FT3 level is if you refuse to give enough T3 hormone to those who do not convert T4 very well? Either you deny us access to T3-based meds, or you restrict our T3 doses to small amounts that make hardly any difference in our FT3 levels.
When will you permit your treated thyroid patients to achieve FT3 levels equal to or higher than the average in UNtreated patients?
Why would you watch our TSH and FT4 levels alone as if they are health outcomes, when they are not? Neither of those hormones can get into the nucleus of cells and activate thyroid hormone receptors. Only T3 hormone can.
Low T3 levels cause hypothyroidism.
From the perspective of organs and tissues beyond the pituitary gland, Low T3 in bloodstream creates a state of hypothyroidism.
In the cell nucleus, T3 binds to the thyroid hormone receptor and enables organs to carry out essential physiological processes. Low availability of T3 hormone means that many T3 receptors in an organ remain unoccupied for a longer duration of time.
The T4 hormone has limited activity in “integrin” receptors on the cell membrane, but has no proven activity in the primary thyroid hormone receptor located in the nucleus of cells.
Science has discovered that the nuclear receptor has a 10-15x increased affinity for T3 compared to T4. We have not discovered what, if anything, T4 can do if or when it binds to the nuclear thyroid hormone receptor — even if it is theorized to have a 1 out of 15 chance of binding to this receptor.
TSH gets nowhere near thyroid hormone receptors. It is not a thyroid hormone (a fact that many forget because it is considered essential to a “thyroid function test”). The physiological role of TSH is primarily to regulate a healthy thyroid gland, which many of us do not have. To a thyroid patient, TSH is like one hand clapping.
This is why its levels are important to monitor in therapy, where FT3 levels are most at risk. We risk T3 loss when we lose a gland whose role is to maintain and defend FT3 levels in blood. (Abdalla & Bianco, 2014)
Once we are on therapy, we are in a medically-manipulated state, so FT3 remains at risk from our therapy modality. Our FT3 is at risk of dropping too low in T4-dominant therapy and of being either too low or too high in T3-dominant therapy.
Abdalla, S. M., & Bianco, A. C. (2014). Defending plasma T3 is a biological priority. Clinical Endocrinology, 81(5), 633–641. https://doi.org/10.1111/cen.12538
Andersen, S., Bruun, N. H., Pedersen, K. M., & Laurberg, P. (2003). Biologic Variation is Important for Interpretation of Thyroid Function Tests. Thyroid, 13(11), 1069–1078. https://doi.org/10.1089/105072503770867237
Andersen, S., Pedersen, K. M., Bruun, N. H., & Laurberg, P. (2002). Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease. The Journal of Clinical Endocrinology & Metabolism, 87(3), 1068–1072. https://doi.org/10.1210/jcem.87.3.8165
Liewendahl, K., Helenius, T., Lamberg, B. A., Mähönen, H., & Wägar, G. (1987). Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy. Acta Endocrinologica, 116(3), 418–424.
Sesmilo, G., Simó, O., Choque, L., & Casamitjana, R. (2011). Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinología y Nutrición (English Edition), 58(1), 9–15. https://doi.org/10.1016/S2173-5093(11)70031-9
Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of Endocrinological Investigation, 25(2), 106–109. https://doi.org/10.1007/BF03343972