Why do the 2012 ATA guidelines dismiss Free T3 testing?
The 2012 ATA guidelines for hypothyroidism mistakenly dismiss Free T3 testing on the basis of the body’s ability to compensate for a lower T4 in certain circumstances. [47 (p. 999)]
To back up their claim, they point to the compensatory mechanisms that one sees in the early stages of subclinical hypothyroidism, namely upregulation of Deiodinase Type 2 that increases conversion from T4 to T3 hormone.
However, these compensatory mechanisms are designed for a temporary deficiency in a state where the thyroid still has some response to TSH stimulation. This state does not necessarily maintain itself over the long term in untreated autoimmune thyroid disease, and it is no longer applicable after L-T4 therapy is able to correct the lower T4.
Once L-T4 therapy begins, Free T3 drops as the T3:T4 ratio shifts (see our section on the Free T3:T4 ratio), and sometimes it drops far too low for health (see our sections on Low T3 Syndrome).
Paradoxically, the article that the 2012 ATA guidelines document cites as its authority for dismissing Free T3 testing happens to strongly recommend Free T3 therapy. The 2001 article they cite concluded that “The main purpose of free T4 and free T3, assays is to distinguish reliably between thyrotoxicosis, hypothyroidism, and the euthyroid state.” 
It would appear to any judicious reader that the guidelines document had updated its consensus on this issue without updating its basis in more recent scholarly research.
Our reluctance to perform the Free T3 blinds doctors to the significantly lower T3 that is seen over the long term in patients on L-T4 monotherapy. In therapy, low T3 can be more extreme in patients with low thyroid volume (as we demonstrate in our discussion of the T3:T4 ratio). It is for this very reason that researchers have long recommend testing Free T3 in patients on L-T4 therapy, and considered it even more useful than Free T4. 
Where is the evidence that the vast majority of hormone-treated thyroid patients are in fact able to maintain not only optimal, but adequate T4-T3 hormone conversion in serum and in peripheral tissues for the rest of their lives?
Thyroid researchers have showed us that “long-term therapy” is where we start to see hormone conversion disorders take their toll (see our section on the T3:T4 ratio)
The health implications of ignoring T3 are tremendous. Compared to the minor non-genomic activity of T4 hormone discovered to date, the T3 hormone is able to initiate genomic action in all thyroid hormone receptors found in the nuclei of cells. [65, 119] All organs and tissues require T3 to generate energy and function properly, and the only way that peripheral organs can obtain T3 is with a sufficient supply of thyroid hormone in serum. Just as a healthy body tightly regulates blood sugar levels, the healthy thyroid gland and thyroid hormone metabolism participate in maintaining stable T3 hormone levels within a healthy range in the bloodstream and within all bodily organs and tissues. [50, 55, 120]
Some doctors are taught that T3 levels vary and therefore tests are unreliable. This is not true, according to research. In untreated healthy humans, Free T3 varies somewhat less within its reference range than the TSH does on a daily cycle. Our T3 levels are normally tied to the TSH circadian rhythm and follow the TSH variation with an approximately 90 minute delay. However, those who depend on L-T4 medication for most or all of their supply may have little to no healthy circadian rhythm in T3 to aid their sleep-wake cycle.
Carefully protected serum levels of T3 are absolutely essential to the health of the cardiovascular system, which depends to a significant degree on this source: “The heart relies mainly on serum T3 because no significant myocyte intracellular deiodinase activity takes place, and it appears that T3, and not T4, is transported into the myocyte.”[86 (p. 1726)] Many components of cardiovascular health have a direct correlation with T3 levels, even subtle changes in levels within the “normal” reference range.[123, 124] Slight reductions of T3 below the individual’s unique set-point can contribute in the long term to classic hypothyroid cardiovascular syndromes such as endothelial dysfunction, impaired diastolic function, increased vascular resistance, and increased homocysteine. [85 (p. 1731) ]
In fact, even in the population at large, Low T3 is just as strong an indicator of myocardial injury as high-sensitivity cardiac troponin T (hs-cTnT) testing. cTnT is now a standard screening tool in emergency departments of hospitals, but researchers advise that hospitals should also use T3 tests in screening their heart patients. [125, 126, 127]
Our scientific research on T3 hormone to date in many fields of medicine beyond endocrinology has been telling us that low T3, not just excess T3, invariably has a harmful effect. Low T3 in bones, joints and brain is more likely in patients with DIO2 genetic polymorphisms that hinder hormone conversion in tissues.
Because of these factors, a minor T3 deficiency in a patient on thyroid therapy can cause more severe hypothyroidism than a larger T4 deficiency. Free T3 levels that are low within reference range can by themselves explain the phenomenon chronic hypothyroid symptoms in the presence of a normal TSH and normal T4. 
TSH and T4 have usurped the Free T3 test’s proper place in therapy. In other words, research and practice itself is afflicted with “low T3 syndrome.”
Endocrinologists all over the world have been dazzled by the TSH testing technology’s quantitative sensitivity and the well-ordered function of the HPT axis in health; this has distracted the field from the thyroid hormone that matters the most to human health. The dogma that Free T3 testing is unnecessary has been accepted on the basis of flawed consensus-based guidelines documents that were carelessly updated.
If Free T3 were regularly tested in hypothyroid therapy, doctors would not as confidently dismiss patients’ continued symptoms when there is a normal TSH and T4.
Hypothyroid patients cannot increase or lower a static daily thyroid hormone dose as TSH rises or falls, both daily and seasonally, and during a woman’s monthly menstrual cycle. To varying degrees, thyroid patients cannot depend on TSH to stimulate more hormone production from a defunct gland. They depend more so on T4-T3 hormone conversion to assist them in adapting, but the three deiodinases involved in conversion can be distorted and unbalanced by their thyroid therapy itself, as discussed in other sections.
Where is the evidence that the vast majority of hormone-treated thyroid patients are in fact able to maintain adequate T4-T3 hormone conversion in serum and in peripheral tissues for the rest of their lives? What if “long-term therapy” is where we start to see hormone conversion disorders take their toll, especially in patients with genetic polymorphisms that can affect conversion?
This blindness to the biological requirement of carefully regulated T3 has very likely caused harm to many hypothyroid patients over the decades. If even a moderately T3-deficient state is extended over months or years in patients on hormone therapy, it can erode their health. Researchers cannot easily study the health implications of Free T3 levels in large populations of hypothyroid patients on therapy if clinicians rarely collect Free T3 data from them.
Next page: Rationale: The T3:T4 ratio
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