Dosing by TSH results in FT3 inequity and health discrimination

The standard measure of thyroid gland health (the TSH normal range) is not a fair or accurate measure of thyroid hormone sufficiency in thyroid therapy.

Normal TSH does not mean

And the same meme, this time with MEN — since men have hypothyroidism too.

Normal TSH does not mean-MEN.png

In a 2015 article, Midgley et al (1) wrote

“the effective TSH level derived in a healthy normal population cannot necessarily be inferred to be equally optimal for a given patient on l-T4 medication.”

Midgley et al and many others have proven that the TSH test is blind and insensitive to low T3 in therapy. As a result, the medical system that trusts in TSH has become blind and insensitive to the chronic suffering of thyroid patients.

The average treated thyroid patient has a lower level of T3, and higher T4, at the same average TSH.

The lower the T3 level is, the more likely are chronic hypothyroid symptoms and long term health problems, especially as we age.

Treating thyroid patients by the TSH alone results in T3 inequity, unnecessary health risks, and human suffering.

Judging our thyroid health by the TSH normal range of health, therefore, amounts to health discrimination against thyroid patients.

What do many patients experience?

  • Our normalized TSH has convinced doctors to dismiss and ignore our subnormal and pathological T3 levels and the debilitating conditions that flow from them.
  • We are left chronically undertreated, symptomatic, and unequal to healthy citizens in our Free T3 levels.
  • We are being declared “normal” in our thyroid levels and therefore the medical attention shifts to other tests, other medications, or merely considering our complaints to be psychosomatic.

Why is this happening?  Our doctors and medical system do not yet acknowledge the amassing scientific evidence on thyroid patients’ very different TSH response to T3.

THE TSH-T3 PARADOX IN THYROID THERAPY

The TSH-T3 relationship is truly paradoxical and abnormal under thyroid therapy.

As Midgley and his co-researchers put it in more academic terms,

“the constitutive equilibria between TSH and thyroid hormones, especially FT3, differ in health and disease.”

Ok, so what’s different for thyroid patients, Midgley and colleagues?

In their study, the higher a thyroid patient’s Free T4, the lower their Free T3 was, despite a normalized or even suppressed TSH, and

“the poorest converters” of T4 hormone “showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001).”

This research finding is clearly inconsistent with the log-linear model of the TSH – thyroid hormone relationship that applies to the UNtreated state and which now dominates thyroid testing and treatment.

Yet the paradox Midgley et al report has been strengthened and confirmed by many other studies. For example,

  • Recent estimates are that up to 15% of patients on L-T4 monotherapy do not respond well to therapy due to insufficient T4 conversion to T3 both in bloodstream and peripheral tissues.(2)
  • Midgley et al’s findings echo the results of a much larger study by Gullo et al, of over 1,800 L-T4 patients compared to a much larger cohort of healthy controls in 2011.(3)
  • In a study of patients before and after total thyroidectomy, patients required TSH-suppressive doses of LT4 to reestablish pre-operative levels of Free T3. (4)

Altogether, the evidence shows that the pituitary gland responds to optimal levels of T3 with a far lower level of TSH secretion in thyroid therapy than in the unmedicated state.

In treated thyroid patients, TSH suppression does not always coexist with thyrotoxicosis or overmedication, and as a result, it does not equate with risk to cardiovascular or bone health.

On the contrary, in patients, TSH suppression may coexist with optimal FT3 and even insufficent T3.

Chronic insufficient T3 does not pose any risk for osteoporosis, but it does pose a severe risk to the cardiovascular system.

THE IMPORTANCE OF TARGETING FREE T3

As explained by Abdalla & Bianco, the healthy human body actively “defends” its FT3 levels around 5.0 pmol/L.

The FT4 and TSH levels modulate within reference range to achieve one goal — to maintain and protect a very steady upper-normal FT3 level.(4)

According to researchers, the healthy human body’s careful protection of upper mid-range FT3 levels implies a biological necessity of maintaining a level of FT3 in the upper half of the reference range.

If optimizing FT3 is the body’s target, and if TSH becomes blind to FT3 in therapy, it follows that it is biologically incorrect and misleading to make normalized TSH the sole target of thyroid therapy.

Indeed, a clinical study in 2018 proved that L-T4 thyroid patients achieved relief from medically-assessed hypothyroid symptoms when their Free T3 was raised into the upper half of reference range, a level that often required suppressed TSH.(5)

Depression is a common symptom of a suboptimal Free T3. Therefore, it does not make sense that antidepressants are handed out like candy to thyroid patients at the mere presentation of depression or cognitive difficulty, when optimizing Free T3 can alleviate or entirely get rid of mental health issues.

PRACTICAL IMPLICATIONS

Midgley et al suggest that

“FT3 measurement may be an additional treatment target”

… besides TSH. We think “may” is rather too gentle and tentative a word.

FT3 ought to be the primary target in thyroid therapy, given the fact that suppressed TSH can coexist with practically any level of FT3 in thyroid therapy, from extremely low to extremely high, and a normalized TSH so frequently means a sub-optimal and symptom-causing FT3 level.

In all modalities of thyroid therapy, measuring the free hormones is a safeguard against both suppressed and elevated Free T3 and Free T4, just as when treating central hypothyroidism.

Just as in central hypothyroidism, a low TSH during therapy does not necessarily signify thyrotoxicosis, because the pituitary response cannot be trusted in therapy.

Measuring Free T3 enables optimization of thyroid therapy modality and dose to alleviate hypothyroid symptoms without resorting to additional medications (such as antidepressants or statins) for conditions caused or worsened by low T3.

Midgley et al recommend aiming for a Free T3 at “the median level typical of the euthyroid controls (>5 pmol/l)”

However, they also caution that

“L-T4 dose escalation may have limited success to raise FT3 appropriately in some cases.”

— This is because the higher FT4 rises within reference range, the less of it will convert to T3 due to ubiquitination. This is why measuring Free T4 is also important — to prevent T4 excess from limiting T3.

Therefore, if alleviation of symptoms and target FT3 cannot be achieved via LT4 dose titration, the researchers say “an alternate treatment modality, possibly T3/T4 combination therapy, should be considered.”

REFERENCES

1. 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557078/

2. 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

2. McAninch, E. A., & Bianco, A. C. (2016). The history and future of treatment of hypothyroidism. Annals of Internal Medicine, 164(1), 50–56. https://doi.org/10.7326/M15-1799

3. Ito M, et al. TSH-suppressive doses of levothyroxine are
required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy. EurJ Endocrinol.
2012;167(3):373-378.

4. 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

5. Larisch, R., Midgley, J. E. M., Dietrich, J. W., & Hoermann, R. (2018). Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer. Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association, 126(9), 546–552. https://doi.org/10.1055/s-0043-125064

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