The thyroid gland is a T3 shield. Defend the unshielded.

You might have heard of a “thyroid shield,” the flexible lead barrier that you wear when you get X-rays taken of your body, neck or teeth.

It’s a good time to remind you to ask for one whenever you’re at risk of xray exposure to the thyroid, which can cause thyroid cancer.

But today my main topic is not thyroid shields, but the way the thyroid gland functions AS a shield, and what happens when we lose part or all of that shield.

According to Etymology Online, the word “Thyroid” comes from the Greek word “thyreos” for “shield.”

The name for shield is derived from “thyra,” meaning “door,” and “-eides” meaning “shape.”

(Back in ancient Greece, some shields were shaped like doors. The top of a shield could protect one’s vulnerable neck, where the thyroid is located.)

In contemporary Western culture we often say the thyroid is the “butterfly-shaped gland.”

But if you see it as the Greeks did, it’s not a delicate, pretty, feminine butterfly.

A shield is an instrument of war, a mighty self-defense. The thyroid gland itself is supposed to protect us! shield us!

In this article, I’ll use Abdalla & Bianco’s 2014 review to show you how the thyroid, with the support of our T4-T3 converting enzymes, defends T3 hormone levels and keeps them very steady in a state of thyroid health.

I’ll use the scientific articles cited by them, especially Laurberg’s review in 1984, to show you how Abdalla and Bianco, despite their wonderful call for a T3 paradigm shift, made mistakes in their statistical reasoning.

Abdalla & Bianco emphasized the physiological importance of bloodstream T3, but they failed to defend vulnerable thyroid patients’ T3 levels enough: They downsized, cropped and limited our T3 pharmaceutical thyroid shield.

I portray our T3 vulnerability and the degree of T3 deficit we may face.

I’ll conclude with a call to action: Let’s each pick up our shields and defend the unshielded, thyroid-disabled people any way we can.

What is being defended? T3.

How appropriate that Abdalla & Bianco’s ground-breaking 2014 scientific review article was titled “Defending plasma T3 is a biological priority.

They help us see the defense system in a new light. Let’s ask their article:

Q) What is the thyroid shielding us from?

A) individually inappropriate blood levels of T3 hormone, in the context of T4 supply.

Abdalla & Bianco point out the stability and precise adjustment of T3 levels over days, weeks and months in healthy people, a stability that is more remarkable than it is for TSH and T4:

Serum TT3 and FT3 exhibit minimal circadian rhythmicity that is due to a nocturnal increase in TSH secretion. 

Otherwise, serum T3 is remarkably stable over periods of days, weeks or months in healthy adult individuals, despite a relatively short half-life (approximately 12–18 h).

Wow, so despite our highly variable circadian rhythm of TSH and T3, they’re saying that over longer time periods, T3 is the most stable of all.

T3’s stability is illustrated by research in 2002 and 2008 that discovered that each individual’s T3 level is more stable from week to week and month to month than their T4 and TSH.

More importantly, the individual’s stable level of Free T3 is narrowly focused only in a small band within the population’s reference range, in relationship to supporting Free T4 and TSH levels, as shown in my overlay of Ankrah-Tetteh’s (2008) three separate graphs.

See Ankrah-Tetteh’s original graphs, overlaid here.

Look at the stability of these TSH-FT4-FT3 “flowers” each standing at a different height within the three reference ranges, each person’s levels measured weekly over 6 weeks.

In people with healthy thyroids, the FT3 level is maintained within the narrow pink petals, a small band of the reference range, in the image above. In some people the FT3 is lower, and in other people, FT3 is stable in the upper half of its reference range. Others have found the same T3 and T4 stability over 12 months.

Now consider that the scale on the y-axis is the percentage of all three reference ranges. The reference range of FT3 was 3.2 pmol/L wide, while the reference range for FT4 was 11 pmol/L wide.

Ankrah-Tetteh and team calculated the “critical difference” for the laboratory values, which is defined as “the smallest difference between sequential laboratory results in a patient which is likely to indicate a true change in the patient” (Jones, 2009). The critical difference for FT3 was at 0.7 pmol/L (21.9% of reference) and for FT4, 2.3 pmol/L (20.9% of reference).

Therefore, FT3 is regulated with extreme precision within each individual, and 0.7 pmol/L variation makes a difference to our bodies, despite the lower concentration of FT3 and its shorter half-life in blood.

Here’s the next mystery: How does T3 stay there? What’s defending and stabilizing its supply in blood? Abdallah and Bianco explain,

“This is likely the result of combined homoeostatic mechanisms involving (i) the hypothalamus– pituitary– thyroid axis as well as (ii) the group of deiodinases.”

T3 hormone levels in blood shield the health of the entire human body, and therefore the body actively defends T3 in blood through backup systems, the healthy HPT axis and the deiodinases, which I’ll briefly explain below.

Abdalla & Bianco herald this view of T3 as the hormone being defended as a major paradigm shift in thyroid science:

“That the level of serum T3 is a main target around which serum T4 and TSH are adjusted constitutes a shift in the paradigm traditionally accepted for the function of the hypothalamus–pituitary–thyroid axis.”

So, if the T3 level in serum is the “target” and TSH and T4 adjust around that target, it shifts the object in the center of the HPT axis away from a pituitary hormone and toward a thyroid hormone that is not T4.

That’s a huge paradigm shift, similar to the one from Copernicus to Galileo.

Renew the paradigm of thyroid therapy

In some ways, the idea of T3 as a sun makes sense. T3’s life-giving influence in every organ and tissue is like the light and heat of the sun. The Earth is at the perfect distance from T3 to support our ecosystems, not too hot (hyperthyroid), not too cold (hypothyroid). Daily circadian variations in sunlight and darkness and the seasons change the ratio.

But no analogy is perfect, and this T3-sun image can only go so far. In our metabolic solar system, T3 levels are vulnerable and need continual defense and daily readjustment.

So let’s move back from the T3 as sun metaphor to the thyroid as shield metaphor…

Let’s ask Abdalla and Bianco what else besides the TSH and T4 adjusts to defend or “shield” T3 levels, given that T3 levels in blood are the target of various physiological defense systems.

Can deiodinase enzymes be a T3 shield?

One of those defense systems they mentioned above is the deiodinases:

“The deiodinase group has the potential to defend serum T3 levels”

(Abdalla & Bianco, 2014)

Q) What is “the deiodinase group?”

A) Our three thyroid-hormone metabolizing enzymes (Deiodinase type 1, 2, and 3 — D1, D2, and D3 regulated by genes Dio1, Dio2, Dio3). They play the role of locally fine-tuning T4-T3 metabolism in specific organs and tissues.

Here’s a quick summary. Our T4 and T3 get transported into cells where they interact with one of these three enzymes in a cell, as I’ve explained earlier, elaborating on Bianco’s 2019 article.

Read and see more in “Visualizing thyroid hormone activity in cells: T3 and RT3 in context
  • A DIO2 enzyme or an upregulated DIO1 enzyme in the cell can transform T4 into active T3, and can transform T3 into an active form of T2, such as 3,5-T2, preparing and “activating” the hormone for signalling before it reaches receptors in the nucleus or mitochondria.
  • In contrast, A DIO3 or downregulated DIO1 enzyme in the cell can transform T4 into Reverse T3 (RT3) that can’t bind to receptors in the cell nucleus, and it can also inactivate T3 into a form of T2, such as 3,3′-T2 that is less capable of binding to receptors.

These three deiodinases work together simultaneously all over our bodies as converted and un-converted thyroid hormones are continually transported in and out of cells, mixing with freshly supplied hormone from any thyroid fragment, plus any pharmaceutical hormone donations.

The deiodinase system actively contributes to, and adjusts, our body’s “global” supply of T3 levels in blood in relation to T4 levels.

The DIOs — how essential are they?

Q) What would happen if both our T4-T3 converting deiodinase enzymes DIO1 and DIO2 were dysfunctional or inactivated?

A) The healthy thyroid gland, guided by our hypothalamus-adjusted pituitary TSH secretion, would defend our serum T3 by pumping out extra T3 that is not being supplied by T4-T3 conversion by deiodinases:

“Experimental evidence indicates that in the absence of T3-producing deiodinases, the hypothalamus–pituitary–thyroid axis resets and is capable of defending serum T3.”

Q) How did scientists learn this through “experimental evidence”?

A) Genetically modified mice that lack DIO1 and DIO2 genes can maintain normal T3 levels as long as they have a functional thyroid gland cooperating with TSH and TRH:

“serum T3 levels are normal in mice with single or combined targeted inactivation of both Dio1 and Dio2 genes.”

So as long as these mice have a thyroid gland shielding their T3 levels, they can compensate for a complete lack of DIO1 and DIO2 function.

Being a DIO1 and DIO2 “knockout” mouse is far worse than just having a genetic “polymorphism” that mildly handicaps a DIO1 or DIO2 gene. Yet they are able to compensate because they have a healthy thyroid gland!

Can the deiodinases shield our T3 without a healthy thyroid?

Abdalla and Bianco ask an important question. Let’s turn the tables on the thyroid-deiodinase relationship:

Would the deiodinases be able to do the same in the absence of a functional thyroid gland?”

Abdalla and Bianco imply the answer is “no.”

Look what they say happens in rats whose thyroids (T3-shields) have been removed:

“Studies in thyroidectomized rats indicate that monotherapy with levothyroxine alone does not normalize serum and tissue T3 and T4 simultaneously at normal TSH levels.”

This is in rats who have functional DIO1 and DIO2 genes. The loss of their thyroid gland has resulted in loss of the ability to maintain both T3 and T4 while the TSH is in the normal range for healthy rats.

The mighty thyroid as T3 shield

Therefore, the functional thyroid gland not only supplies T4 but actively defends T3 in serum. The pituitary TSH and hypothalamic TRH cooperate with thyroid tissue as part of the “HPT axis,” shifting the ratio of T3:T4 secretion to boost the T3 portion more as TSH rises.

  • The healthy thyroid gland is our most essential T3 shield, supported by TSH.
  • The deiodinases (DIOs) help to provide a baseline of T4-T3 conversion but they can’t always “top up” enough when T3 falls short, when there’s not enough TSH-stimulated healthy thyroid tissue.

Laurberg back in 1984, whose article Abdalla and Bianco cited, deduced that thyroidal T3 secretion is incredibly flexible, able to function as a nimble “T3 shield” to protect the healthy person or the more vulnerable untreated hypothyroid person:

“the thyroid gland, through a number of mechanisms, possesses the ability to increase its contribution to total T3 production.”

How T3-shielding happens through synthesis and conversion

Beginning with insights from Laurberg’s review in 1984, thyroid science has come to understand the dual role of the thyroid gland.

  1. The thyroid synthesizes both T4 and T3.
  2. And the thyroid converts T4 to T3.

1+2 = 3, the thyroid’s overall secretion rate and T4:T3 secretion ratio.

What stimulates both 1 and 2 to be richer in T3? A higher TSH. Our normal circadian fluctuations and individual variation in TSH stimulation levels shift T3 secretion as blood flows through the thyroid gland.

Next, these two processes are locked in a reciprocal synergy, like two hands clapping. A shift in the ratio of T4:T3 synthesis directly affects the rate of T4-T3 conversion. Synthesis can have a positive or negative influence on conversion.

To use a financial analogy, when you have more money to invest,

  • If you deposit into both T4 and T3 accounts but boost your investment in T3 by a slightly higher amount, you get a higher “interest rate” that pays you back in more T3.
  • On the other hand, the more “excess” T4 you invest in, the less of it converts to T3 in interest or profit; imagine the marketplace being overloaded with T4 beyond demand.

If you want to know how, Abdalla and Bianco themselves reviewed the process of “ubiquitination,” which we’ve explained in a separate post.

Abdalla and Bianco mounted a poor defense. No T3 shielding from them!

Q) Why isn’t anyone taking this 2014 article seriously? Why wasn’t it successful in inciting the T3 paradigm shift?

A) Because Abdalla and Bianco’s article on the “defense” of T3 contradicts itself. It limits the thyroid gland’s defense by putting a false numeric ceiling on its T3 secretion!

A powerful thyroid myth, still operative in 2020, blinded them back in 2014.

Look at this myth of the minimal and limited T3 support provided by the healthy thyroid gland:

“Most T3 is produced outside the thyroid gland via deiodination of T4, with <20% being secreted directly from the thyroid.”

Why choose to say “less than 20%” when Pilo’s 1990 article said average 20%? There’s a big difference between less than (<) and an average.

… and this is 80/20% myth is followed by its usual sidekick, the numerically narrow average ratio of T4:T3 secretion:

The molar ratio of T4 to T3 in the human thyroglobulin is 15:1, and some estimates put the thyroidal secretion as containing a molar ratio of 11:1″

(Some authors put the number for T4 first, while others invert the order. Here it is 11 moles T4 to 1 mole T3.)

I’ve added bold on “the” because such grammar makes it seem like this applies to any and all thyroids in all humans, when it certainly does not.

Shockingly, this T3-diminishing, confining way of talking about thyroidal T3 secretion can’t be justified by the articles they cite!

It is clearly an error for Abdalla and Bianco to say “some estimates put the thyroidal secretion as containing a molar ratio of 11:1” when, according to their cited articles (and the articles cited by those articles), that was Larsen’s 1975 finding in extracted thyroid gland tissue sitting on the lab bench, not the ratio that the thyroid glands would be actively “secreting” in health.

An 8 to 1 in vivo secretion rate, found by Tegler, 1982, was highlighted by Laurberg, 1984, whom Abdalla and Bianco cite. But Abdalla and Bianco chose not to echo that finding in this study.

Unfortunately, in these old studies, they could cheat. They could obtain the average T4:T3 secretion ratio they wanted by selecting not just methods, but patients.

  • Select people with higher TSH values, and you can be sure their thyroid gland tissue would boost T3 secretion preferentially.
  • Alternatively, with a lower average TSH in your cohort, you get a lower percentage of T3 secreted from their thyroids, on average.

What kind of T4:T3 ratio would you like to obtain as a result of your experiment? Just pick your patients carefully and screen them by their TSH, because you can manipulate the ratio that way.

Now do you see the 15:1, 11:1 and 8:1 secretion ratios in a different light? There is no static ratio. There is no single ratio that represents every individual.

An average ratio is not as important as the flexible function of the thyroid gland. These ratios are snapshots of a moving object, showing the wide variety of T4:T3 ratios that the thyroid can secrete to shield your T3 and keep you healthy.

Advanced scientific readers click here: Reveal more about the sources Abdalla & Bianco cited but did not read carefully enough.

What did the cited articles say about the wide range of T3-secreting capacity in the thyroid?

If you follow the full trail of citations on Abdalla and Bianco’s review of secretion and conversion rates, you will find a web of research articles from the 1970s and 1980s.

For example, a 1977 article by Izumi and Larsen, the “healthy controls” consisted of only six (6) extracted thyroid glands from patients of nonspecified age or gender who underwent surgery for thyroid nodules. The individual glands had a T4:T3 ratio of “7.2 to 1” to “18:1” with an average of 13:1 bound to thyroglobulin. However, the diversity and wide range across the 6 thyroids was tremendous:

  • The thyroid with the most T3 contained 6.08x the amount of the thyroid gland with the least T3
  • The thyroid with the most T4 contained 11.21x the amount of the thyroid gland with the least T4.

But the “content” of a thyroid’s T4/T3 ratio is not as T3-rich as its “secretion” ratio.

Laurberg’s 1984 review article, cited by Abdalla and Bianco, clearly explained that the content of a removed thyroid gland can’t be confused with the secretion ratio of a living gland.

When actively stimulated by TSH in blood, the thyroid gland not only synthesizes T3 and stores it in thyroglobulin, but the thyroid also converts a variable amount of T4 to T3 as blood flows through it, and this thyroidal T4-T3 conversion rate boosts the “secretion rate.”

  • Secretion ratio = Thyroglobulin T4/T3 content ratio + Thyroidal T4-T3 conversion rate.

Laurberg cited a study of 15 euthyroid patients during surgery. They found a huge discrepancy in the T4/T3 ratio of tissue content vs. the ratio of active secretion:

“15 euthyroid patients studied during thyroid or parathyroid surgery. The average T4/T3 ratio in thyroid tissue was 12.6 (mol/ mol) and that of thyroid secretion 8.0 (P < 0.05).”

The study that yielded the 8.0 to 1 ratio of T4:T3 thyroidal secretion was measured hormone levels directly while patients were in surgery. These secretion rates were measured, not just estimated based on a theoretical model as Pilo’s rates were. Clearly, the secretion ratio prefers T3 more strongly, a T4/T3 ratio of 8:1.

The thyroid shifts T4/T3 ratio to shield plasma T3 in untreated hypothyroidism

In untreated hypothyroidism, when more TSH stimulates the dying thyroid, the ratio shifts even more powerfully toward T3 secretion.

The 1982 kinetic study by Faber and team estimated the following T3 production rates and ratios (nmol per day per 70 kg):

T4 mean (range)T3 mean (range)T4/T3 ratio
(*T3/T4 ratio)
Controls (8)117 (89-166)39 (28-47)3 to 1 (*0.33)
Hyperthyroid (8)381 (247-564)430 (112-497)0.88 to 1 (*1.12)
Hypothyroid (8)4.3 (3.1-11)6.4 (2.5-8.9)0.67 to 1 (*1.48)
*calculation added by T. S. Smith,

Of course, the above “production rates” involve more than T3 from thyroidal secretion. They include all the T3 converted from T4 throughout the body per day. (I will get back to the implications for the “secretion rate” in a minute.)

Above, notice how Faber’s 1982 article always included the wide range of human diversity in parentheses next to the mean — a wise choice given only 8 people studied per category.

Also very wisely, Laurberg in 1984 did not put a ceiling on the thyroid gland’s capacity to defend plasma T3 at “20% of the daily T3 production rate.”

Instead, Laurberg used his overall review of the literature, especially Faber’s 1982 table summarized above, to make this argument that untreated hypothyroid patients a higher percentage of their T3 from their thyroid glands:

“the average daily production of T3 was found to be higher than that of T4 in hypothyroidism. This suggests that a relatively large amount of the circulating T3 originates from the thyroid in these patients too.”

Laurberg reasoned that contributing to that production rate, the percentage of T3 from thyroidal secretion was undoubtedly enlarged far beyond the 20% seen in healthy controls, as well.

Abdalla and Bianco did little to nothing for vulnerable patients in need of a T3 shield. If they truly believed in their paradigm shift, they would have taken a stand for vulnerable human beings.

Instead, they wrote things like this, based on the averages from Pilo et al, 1990:

“It is estimated that healthy adult subjects produce about 30 µg T3/day, of which about 5 µg are secreted directly from the thyroid and the rest is produced outside of the thyroid parenchyma via T4 deiodination.”

How wrong can you be? Let’s look at the actual range of thyroidal T3 percentages per day from Pilo et al, 1990 across 14 people:

Q) How many micrograms of T3 per day was estimated to come from the thyroid gland in these 14 people, if you multiply their secretion rate by their body surface area?

A) Between 1.5 and 14.2 mcg.

Q) How much did the thyroid contribute to the daily T3 production rate in the person who had a T3 secretion rate of 14.2 mcg per day?

14.2 mcg out of 33.9 mcg total T3 production rate = 41.88%

Serious implications for individual thyroid patients

What are you going to do to defend the T3 supply of this 31 year old man after you remove his thyroid gland? Give him T4 monotherapy and tell him “go convert your own T3 in your liver and kidney and other organs”?

According to Laurberg’s sources in 1984, on standard T4 monotherapy, he may end up with a deficit of 15 to 35% less T3 than he would have had with his healthy thyroid.

Historical biases in thyroid science

These kinetic studies’ models, cumulatively adjusted over history among researchers, were imprecise, building on assumptions and technical assay methods that would later change.

Abdalla and Bianco, when generalizing about these kinetic studies’ statistics, do not point out that many of these old studies were performed before we understood there were three deiodinase enzymes that convert thyroid hormones. Their models are incorrect and outdated.

Some of the people Abdalla and Bianco cite, like Izumi and Larsen, reduced the wide range of data from very few thyroid glands to narrow average ratios. Others, like Laurberg and Faber, expressed the wide diversity and range of T3 secretion among their small data sets.

Moreover, no single T3:T4 ratio can be representative of all individuals if a data set had no central tendency.

But it did not take long before endocrinologists began to use these narrow ratios, based on kinetic studies, to reduce the apparent complexity of the thyroid hormone economy.

They started to use the naked averages to build simplistic models of “the” HPT axis and “the” human thyroid that numerically dismissed human variation, like Abdalla and Bianco do.

These models were built at a time when dessicated thyroid (NDT) was gradually being questioned as the gold standard of hypothyroid therapy. Those who favored T4 monotherapy (such as Larsen, whose work has strongly influenced Bianco as repeated co-author) minimized T3 secretion as much as they could in contrast with T4-T3 conversion, ignoring the healthy euthyroid people who secreted significantly more than 20% of their daily T3 supply. They also minimized the human diversity among T3 secretion levels as much as they could, in part to justify their promotion of T4 monotherapy for all.

Abdalla and Bianco should have been more cautious.

Research studies are called “kinetic” studies when they follow substances from their appearance in blood to their clearance. They use that to estimate how much T4 and T3 were secreted, and how much T3 came from conversion after secretion.

One of the articles Abdalla and Bianco cite, by Laurberg in 1984, cautioned about the misuse of the average (the statistical mean) to create generalized theories and models:

“Kinetic studies are complicated and caution should be exercised when trying to develop models from mean values obtained from relatively few subjects in such studies.”

If Abdalla and Bianco had read Laurberg’s 1984 article carefully, they would have noticed that the mean values of T3 secretion can’t accurately represent the wide-ranging flexibility and defensive function of the thyroid’s T3 secretion.

By focusing on the mean/average secretion rates in a small number of selected patients as if an average was a speed limit sign for the thyroid gland, Abdalla and Bianco mathematically minimized the extent to which this vital gland alters its secretion rate and ratio to defend T3 levels. They undermined their article’s core argument.

The loss of our T3-shielding thyroid gland

Q) Oh no, what if our main shield, the thyroid gland itself, has been damaged, attacked, removed?

A) Now we are far more vulnerable to T3 loss.

So how do we protect against T3 loss? We take thyroid meds.

Q) Can T4 medication function as a T3 shield?

A) It depends.

  1. How much of your thyroid tissue remains? Thyroid tissue is very rich in D1 and D2 enzymes that can help you convert T4 to T3. Even a little thyroid tissue can provide a lot of D1 and D2, which can function even without a TSH boost.
  2. How healthy are your DIO1 and DIO2 enzymes? Are you a “good converter” of T4? Check your Free T3:T4 ratio to find out. Analyze your ratio using Gullo’s 2011 reference ranges for the ratio, and/or by using the SPINA-Thyr analysis program.
  3. Are you permitted to dose T4 to a level that will provide you enough T3? Our medical system uses TSH to adjust dosing of T4 while being blind to T3. This is the opposite of what Abdalla and Bianco says the body does. The body keeps its eye on the T3 level and T3:T4 ratio as the “therapy target.”

After your thyroid is mostly dead or removed, you may discover that your deiodinase enzymes are inefficient at shielding blood levels of T3.

Laurberg did the math on the T3 deficit, citing no less than five prior sources to calculate its range. He quantified the discrepancy in T4/T3 ratios between healthy controls and treated thyroid patients on LT4 monotherapy:

“in patients receiving replacement or suppression therapy with T4 alone […] serum T3 is 65% – 85% of the values expected from the serum T4/T3 ratio in normal subjects.”

If you do the inverse of this math, this means thyroid-disabled patients can have up to a 35% T3 deficit compared to healthy-thyroid people if they are only treated with T4 hormone after the loss of their thyroid function.

One of the many sources Laurberg cited in the sentence above was Ingbar et al, 1982, which plotted the Total T3:T4 ratios in LT4 monotherapy to illustrate where they fell compared to healthy controls.

Ingbar and team wrote, in explanation of this graph, that

Overall, the mean serum T3/T4 ratios were about one-third lower in patients receiving Synthroid than in the euthyroid controls.

In T4 monotherapy, if you body wants to achieve Total T3 levels between 90-120 ng/dL, you have to pay for it by providing a higher than average Total T4.

In addition, the variation among patients’ T3 levels was twice as high as it was in healthy controls — likely due to the lack of thyroidal T3-shielding in the patients being treated for hypothyroidism:

T3 / T4 ratios in the [Synthroid group] varied much more widely [than in the control group]. The coefficient of variation of the ratio in those taking Synthroid® was 36.2% and in the controI group was 16.1%.”

In the context of the graph above, this variation means you have a higher chance of losing T3 than gaining it. There are only 2 dots above 120 ng/dL, but many dots under 90 ng/dL.

Measuring the T3/T4 ratio and T3 levels during therapy is helpful since T3 loss occurs far more often during thyroid therapy than outside of it.

You cannot predict how much T3 you will lose. The TSH is not predictive of T3 levels (many with sufficient T3 in blood had a suppressed TSH). The T4 level is only a little better than TSH at predicting T3 levels (lower-normal T4 levels are usually ineffective at achieving T3 sufficiency in blood while one is dosed on T4 hormone).

The most T3-shielding sentence of Ingbar’s article is worth highlighting. Measuring T3 functions a confirmation of clinical euthyroidism:

“From our experience, it would appear that, in patients receiving levothyroxine, the serum T3 concentration is a more reliable indicator of the metabolic state of the patient than the serum T4 concentration is.”

In addition, the risk of overdose is only present when the T3 and T4 are both elevated together:

barring clear elevations in both serum T4 and serum T3 concentrations, one is left with clinical evaluation as the sole means of recognizing overdose in patients receiving levothyroxine therapy.”

In other words, they understood that thyrotoxicosis cannot be caused by low TSH in isolation or by high T4 + low TSH. An elevated T3 level must participate with an elevated T4 level to cause clinical manifestations of overdose.

Ingbar’s entire article had the purpose of clarifying that neither TSH suppression nor statistical T4 excess indicated true overdose during T4 monotherapy. Ingbar entirely excused a statistically elevated T4 that suppressed TSH, as long as it did not also elevate T3 at the same time as T4.

Does Reverse T3 prevent us from shielding T3?

No. The Reverse T3 hormone is not a metabolic obstacle to T4-T3 conversion, despite internet myths that claim the opposite.

Ingbar’s team found no proof that some patients’ poor T3:T4 ratios were “caused by” their T4 conversion to Reverse T3, despite honestly highlighting the T3:T4 ratio loss in T4-treated patients.

Nevertheless, they clarified that some diagnostic insight can be gained by measuring RT3, if it is interpreted properly.

Here are their words on RT3:

“Although [RT3] concentrations were clearly increased in many patients, the extent of [RT3] increase was proportional to the elevation in the serum T4 concentration. This was evidenced by normal values of the serum rT3 / T4 concentration ratio and the highly significant positive correlation between serum T4 and rT3 concentrations in individual specimens.

Further, the lack of correlation between serum rT3 / T4 and serum T3/T4 concentration ratios differentiate patients receiving levothyroxine from those with systemic illness, in whom these ratios are negatively correlated.”

Let’s unpack this significant quote bit by bit.

First of all, their study revealed the correlation between T4 and RT3 remained similar across controls and T4-dosed patients. Both groups had similar rT3/T4 ratios. In healthy, non-overdosed T4 patients, a normal T4-RT3 conversion rate was maintained just as it was in healthy undosed people.

Secondly, the rT3/T4 ratio did not correlate with T3/T4 ratios in individuals. A rise in RT3 did not correlate with a drop in T4-T3 conversion rate.

The human body doesn’t have to choose between optimized T3 and higher-normal RT3; these two hormones can peacefully coexist. Higher RT3 does not on its own indicate a global rate of T3 loss in cells. The deeper explanation that Deiodinase type 3 plays the T3 blocking role came two approximately decades after Ingbar wrote in 1982, but his team saw the effects of this phenomenon very clearly.

This lack of correlation between two ratios is a significant finding because, as they explained, a rise in the RT3/T4 ratio together with a correspondingly lower T3/T4 ratio (a negative correlation between two ratios) helps to identify true cases of “systemic illness,” which later acquired the name Nonthyroidal Illness Syndrome (NTIS).

Only when two ratios are compared (higher RT3/T4 ratio + lower T3/T4 ratio) can one discern the thyroid metabolic derangement that goes hand in hand with systemic illness during NTIS.

Reverse T3 levels in isolation from both T3 and T4 are impossible to interpret properly. However, RT3 in relationship to other hormones becomes an aid in differential diagnosis. It helps differentiate between T4 overdose/underdose, a baseline poor T4-T3 conversion rate during health, and NTIS.

The lack of negative correlation between these two ratios indicates that the thyroid hormone manifestations of NTIS syndrome are not present in undosed or T4-dosed people in their study. This fact was consistent with their patients’ clinical presentation.

By implication, the T3/RT3 ratio used by other researchers (not mentioned by Ingbar) is not sufficient because that ratio is blind to fluctuations in T4. The T4 hormone is the only origin of RT3 molecules in the body. The T3/RT3 ratio will fail to rule in or rule out NTIS, but it may supply staging information in cases where NTIS is known.

So please, let’s “stop the Reverse T3 madness” and get back to the body’s main goal of shielding T3 — because regardless of what your RT3 levels are, T3 is at risk.

Pharmaceuticals as T3 shields?

Our thyroid medications now need to shield us from an individually suboptimal T3.

For many people, T4 monotherapy is enough of a boost. Some people have a partially functioning thryoid fragment to cooperate with a T4 thyroid pharmaceutical. Even a little fragment of thyroid tissue may work as a partial T3-shield because it still contains deiodinases that convert T4 to T3, and thyroid tissue is far more richer in DIO1 and DIO2 than any other gland in the human body, yes richer than liver or kidney.

Others have utterly lost their thyroid gland to complete autoimmune fibrosis, atrophy, or to removal from thyroid cancer, or radioactive ablation after Graves’ disease.

Now recall what Abdalla and Bianco said about the loss of the thyroid gland. The deiodinases in the rest of our body do not always compensate for thyroid loss. With thyroid loss, we are exposed to the risk of T3 loss.

Now add that to Laurberg’s summary that up to 35% of T3 may be lost in some people on LT4 monotherapy, compared to the T3:T4 ratios and levels of the healthy-thyroid population, and Ingbar’s “out of the box” graphic illustration of some of that loss.

If we do not convert T4 hormone at a healthy rate, we may need to reach out to T3 thyroid medications need to give our bloodstream “enough” T3 hormone, not just T4 hormone, to compensate for thyroid gland function plus the loss of thyroid-tissue deiodinases that convert T4.

What if a thyroid-disabled person also had a genetic polymorphism in DIO1 or DIO2, or a chronic health condition that upregulated DIO3 and increased the rate of T4 and T3 deactivation? Wouldn’t some people need even more T3 than the “average” thyroidless or thyroid-damaged person to compensate for a further loss caused by poor deiodinase function and T3 loss in chronic illness? Yes, it’s likely. Abdalla and Bianco admit this.

That’s where T3 pharmaceuticals and desiccated thyroid (NDT) play an important therapeutic role. They provide a richer T3:T4 ratio that may be “physiologically correct” for that individual when it compensates for their thyroidal handicaps and T4-T3 metabolism handicaps.

Downsizing the pharmaceutical T3 shield in clinical trials

Unfortunately, Abdalla and Bianco fall into a trap again in their article’s review of T3-T4 combination therapy studies by reducing all “combination therapy” only to studies that adopted the narrow thyroidal T4:T3 secretion ratio estimates (14:1 to 10:1). They accepted these studies’ methods and results as valid and used them to argue for a slow-release T3 formulation.

The criticisms of this clinical trial tradition ought to clarified:

  • Who has declared it medically valid to use, as a pharmaceutical dosing formula, estimated statistical averages of secretion from kinetic studies — such as Pilo’s study on 14 healthy people overdosed with iodine? A kinetic study is not a prescription or a preclinical trial. A real healthy thyroid gland would adjust secretion ratios daily and weekly far more than a rigid pharmaceutical trial. A rigid model of “the healthy thyroid gland” is not adaptable to the therapeutic reality of adjusting the dosing ratio to the patient while considering their plasma FT3 and FT4 ratios and clinical presentation.
  • One simply cannot generalize about “combination therapy” when reviewing these limited studies. Combination therapy includes all ratios of T3 and T4 used in combination, including the T3-richer 4.2 to 1 ratios found in desiccated thyroid (NDT). Published in 2014, this article does not cite the NDT randomized controlled trial by Hoang et al. in 2013, though it, too, was flawed.
  • Limiting T3 supplementation refuses to respect the thyroid’s “shielding” principle of more T3 compensation for less T4. In other words, such studies minimize T3 supplementation to a level far lower than the thyroid gland itself is capable of when inducing T3-based euthyroidism to compensate for T4.
  • Such studies are blind to the HPT axis’s feedforward principle that adjusts T3 secretion to target a healthy FT3:FT4 ratio for the individual. If the T3 paradigm shift Abdalla and Bianco articulate has a basis in physiology, then the thyroidal T3-shield aims to defend individualized FT3 levels and FT3:FT4 ratios, and the TSH is merely a means to that end in a person with a healthy thyroid gland. Targeting a level of TSH negative feedback in a person who can no longer fully benefit from TSH feedforward stimulation to boost T3 levels is biologically foolish.

This tradition of clinical research has chosen a very narrow and exclusive ratio to fight a straw-man battle with an aim to defend a therapy policy. These trials have not been about achieving clinical benefit, but about protecting a medical ideology.

T4 monotherapy is equipped with no T3 shield, so they’ve tried to rebalance the odds by limiting the size of the combination therapy’s T3 shield.

When you rig the game by enforcing a handicap on the trial medication’s greatest asset, you can claim that the trial ratio failed to achieve superiority over T4 monotherapy. In reality, the rigged trials prove T4 monotherapy is neither inferior nor superior to a weak and narrow T3:T4 dosing ratio when both therapies are applied rigidly and blindly to a set of people already accustomed to T4 monotherapy alone.

Across the broader historical scope of thyroid therapy, T3-rich medication has been available as our shield. To many patients they are a far stronger shield than mere T4 supplementation alone — but only when T3 or desiccated thyroid dosing is untrammeled by these petty, unphysiological limits on T3-T4 combination dosing ratios.

Our medical system fails to defend individually-optimized T3

Q) Now, can you see how deceptive statistics and a TSH-centric paradigm have skewed the thyroid medical system away from active T3-defense of the defenseless?

A) Evidence: Six years later in 2020, we’re still waiting for Abdalla & Bianco’s “paradigm shift” to arrive in doctors’ offices and laboratory testing policies, and it’s no surprise that nothing has shifted yet, as the TSH-T4 paradigm is deeply institutionalized.

  • We’re judged euthyroid or hypothyroid by our TSH alone, as if it’s an omniscient god that is capable of knowing the T3 circulating in our elbow or left toe, as if it’s an omnipotent god raising our night-time T3 secretion without a cooperating healthy thyroid. There will be no Galileo-like paradigm shift for thyroid science until doctors understand that the body is just using TSH as a means to an end — the most urgent and essential purpose of TSH is to collaborate with the thyroid gland to protect the most precious thyroid hormone, T3. If TSH can’t do that #1 job, who is going to double-check that TSH is failing to defend our T3?
  • Our Free T3 and Free T4 tests are cancelled by laboratory flowcharts so that our doctors cannot calculate our Free T3:T4 ratio and analyze our “global deiodinase efficiency” using free desktop endocrinology research tools like SPINA-Thyr. What a society fails to measure, it fails to value. T3 is the most potent thyroid hormone, and Abdalla and Bianco pointed to the importance of stable and individually-optimized T3 levels, and yet nobody cares to monitor how much we’re getting out of our therapy and into the circulating blood? Don’t they know our hearts, livers, and kidneys depend on Free T3 far more than our pituitary does, according to thyroid science? It’s mind-numbing to see the extent of TSH-centric, dogma-driven, T3 blindness.
  • We’re routinely placed on T4 monotherapy at diagnosis without informed consent regarding its pros and cons. We may inadvertently receive a T3-ectomy. If a person begins thyroid therapy today in 2020, she or he won’t likely be informed of the other options for thyroid therapy, because therapy guidelines have institutionalized thyroid pharma prejudice and have supported pharmaceutical market manipulation.
  • We are rarely permitted T3 therapy when T4 monotherapy fails to give us sufficient T3. Instead of directing doctors to interpret our Free T3:T4 ratios (which would require testing both), guidelines tell doctors that every other disease under the sun could, and therefore should, take the blame for our symptoms, poor health, and discontent. Doctors are not told that the reduction of T3 is capable of worsening almost every health condition on the standard list of things to blame, because those chapters on the body-wide effects of hypothyroidism have been removed from the advanced endocrinology textbook for thyroid.
  • We’re often told to “eat less and exercise more,” two things that, if we take to the extreme, can decrease our TSH levels and T4-T3 conversion rates and leave us with even less T3. How is that helpful?

How can compassionate doctors and paradigm-shifters see the necessity of individually-appropriate T3 levels and yet neglect to measure and defend our T3 levels and T3:T4 ratios? All we ask for is what healthy-thyroid persons enjoy, an individualized optimization of T3 that results in freedom from both hypothyroidism and hyperthryoidism in all tissues.

What can we do to shield T3 in unshielded people?

Our role, if we are willing to take up the noble mission to defend the T3-defenseless, is to “shield” vulnerable people from individual T3 loss.

Just as the body’s natural T3 shield adjusts its secretion ratio and rate, so dosing must adjust to the individual body’s response to pharmaceuticals and the FT3:FT4 ratios they obtain in blood. The overall aim is to supply thyroid treatment based on the individual’s T3 needs in relationship to their range of global T4-T3 conversion rates.

Stop the misuse of the narrow average ratios of thyroidal T3 secretion estimated from small groups healthy-thyroid people in articles from 1990 and earlier. Respect the wide range and diversity of human T3 secretion.

Stop the thyroid pharma prejudice that dismisses or forbids T3-dominant ratios in thyroid medication, and accept that there is no single “physiologically correct” T4:T3 dosing ratio that applies to all humans. All thyroid pharmaceuticals can be used alone or in combinations as safe and effective therapeutic tools, when they are adapted to the individual more than to rigid policies.

Stop the biochemical bigotry that misunderstands and misuses statistical reference ranges for TSH, Free T4 and Free T3, leaving patients un-optimized, imprisoning them in individually T3-deficient states, wrongly believing that anywhere in the reference range is protective of health and all levels outside of them signify risk of illness.

Be watchful of unethical discrimination against thyroid patients’ sex (“you’re just stressed from being a working mom”), age (“you’re too old for that dose”), cognitive decline and emotional instability (often a result of poorly defended T3 levels), physical attractiveness (weight gain and hair loss is not our fault), and concurrent medical disabilities (“we can’t give you T3 because you have a heart condition”). Consider pregnancy status: Pregnant women will get more oversight of thyroid levels than women undergoing a difficult transition in menopause.

Reduce economic barriers that force patients to pay an unfairly high price for essential hormone tests that can explain or prevent years of suffering, the price of more expensive yet equally essential pharmaceuticals obtained farther from home, and the price of specialized doctors who fill the thyroid-shaped knowledge gaps in insured health providers’ services.

Thyroid warriors, stand firm and hold up your shields!

Tania S. Smith

Read our post : Healthier thyroid warriors: Our fight is not over.


Abdalla, S. M., & Bianco, A. C. (2014). Defending plasma T3 is a biological priority. Clinical Endocrinology, 81(5), 633–641.

Faber, J., Lumholtz, I. B., Kirkegaard, C., Siersbaek-Nielsen, K., & Friis, T. (1982). Metabolic clearance and production rates of 3.3’-diiodothyronine, 3’,5’-diiodothyronine and 3’-monoiodothyronine in hyper- and hypothyroidism. Clinical Endocrinology, 16(2), 199–206.

Hoang, T. D., Olsen, C. H., Mai, V. Q., Clyde, P. W., & Shakir, M. K. M. (2013). Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study. The Journal of Clinical Endocrinology & Metabolism, 98(5), 1982–1990.

Ingbar, J. C., Borges, M., Iflah, S., Kleinmann, R. E., Braverman, L. E., & Ingbar, S. H. (1982). Elevated serum thyroxine concentration in patients receiving “replacement” doses of levothyroxine. Journal of Endocrinological Investigation, 5(2), 77–85.

Izumi, M., & Larsen, P. R. (1977). Triiodothyronine, thyroxine, and iodine in purified thyroglobulin from patients with Graves’ disease. The Journal of Clinical Investigation, 59(6), 1105–1112.

Laurberg, P. (1984). Mechanisms governing the relative proportions of thyroxine and 3,5,3’-triiodothyronine in thyroid secretion. Metabolism: Clinical and Experimental, 33(4), 379–392.

Tegler, L., Gillquist, J., Lindvall, R., Almqvist, S., & Roos, P. (1983). Thyroid Hormone Secretion Rates: Response to Endogenous and Exogenous Tsh in Man During Surgery*. Clinical Endocrinology, 18(1), 1–9.

18 thoughts on “The thyroid gland is a T3 shield. Defend the unshielded.

  1. I sit here and look at the Ankrah-Tetteh study. I quistion the validity of the findings in the study. It says blood drawn between 12 30 and 14 30. When I see that TSH is at 2 for some, and 3,5 for subject nr 7. These TSH levels would be maybe even over reference if drawn at 8 AM. But subject 7 has the highest TSH, Ft4 and Ft3. I find the numbers very puzzling. Some of these people would be considered hypo thyroid. So many patients come to the groups reporting symptoms with numbers like this. They don’t say anything about the subjects other than they were healthy. I find it strange that the numbers differ so much from the Guillo et al study, where there were after all, 3800 subjects. I just find it puzzling that so many of the subjects have what we would consider a slightly elevated TSH. I guess I don’t trust this study 100%.

    1. Thanks for your intelligent comment, Liv.

      True, given our knowledge of the circadian rhythms of TSH and FT3, the blood draw in the afternoon is at the time when TSH is generally lowest for the day. I think the main value of the study is in the stability of levels over time per person, and the individuality of levels in contrast with other individuals, and beyond that, a lot of these results could be questioned — but we lack clinical data to interpret them properly, and so we are left with hypotheses!

      When I look at subject 7, I see a person whose higher TSH is effectively stimulating higher T3 and T4 production. Six weeks is a long time for all three levels to be stable, so some thyroid scientists would say they have an adjusted metabolic setpoint. I recall that numbers like these can be seen in metabolic syndrome with obesity. These people weren’t obese, though, with “mean body mass index 21.3, range 19.0–25.9.” Dr. Hoermann has written an article in 2017 on “set point alterations” that in Androgen deprivation therapy (ADT) for prostate cancer, men develop insulin resistance and altered body composition. Their TSH rises due to leptin, on average +0.69, along with a rise in FT4 by avg 2.2 pmol/L, and their T4-T3 conversion is reduced a little, so their FT3 remains stable. So some strange things occur when we fiddle with sex hormones, insulin, and glucose.

      The people with the lower T4+T3 levels also make me feel uncomfortable just because I see how patients on hypothyroid therapy suffer at that part of the reference range. On the other hand, these are levels that one sees even in healthy aged people. It is very possible that the entire metabolic system just runs a lot better with a healthy thyroid gland even when the numbers are low-normal, given that these people could have had a HUGE daily circadian rhythm that is not captured in the data set when tested at this time of day. What would these people’s 3AM levels of TSH and FT3 look like? If they are truly healthy, my guess is that they’d both be way higher.

      1. This study needs to be replicated under more strict conditions. I agree that the main point is the stability interindividually. But stating someone is healthy is not good enough when it comes to the thyroid. Gullo et al have really tried to make sure, participants really are thyroid healthy. I think these with the lowest numbers are hypothyroid. And not only subclinically according to the current Norwegian TSH range, which goes to 3,6. I trust Gullo more. But I will include Russell et al’s numbers to my Optimal levels info, where I discuss normal levels. The numbers from Russell et al are higher than Gullo”s. They were around 30 young people. I would think, age plays into it.
        But the article is interesting, and it’s very important for us patients, to what degree an intact thyoid matters. Very important clinical implucations. Not only for T3 medicating, but also for focus on antibodies and the treating of those.
        Be well😊

    2. Just replying more — Yeah, the Gullo et al 2011 study on levothyroxine, with 3,800+ controls, had a band of control subjects with high-normal and low-normal TSH… the TSH levels divided the subjects into quintiles (5 levels), and most of them were in the 0.40-1.00 TSH quintile.

      I really, truly wish they had also given us tables with FT3 levels dividing their populations into quintiles, and another with FT4 levels in quintiles.

      The most surprising fact in Gullo is that they found FT3:FT4 ratios remained remarkably stable at all levels of TSH, around 0.32 pmol/L in healthy controls, and that the average FT3 was very stable in healthy controls.

      Even in Gullo’s healthy cohort with the highest TSH level, the average FT3 was the same and the average FT3:FT4 ratio was the same, except for a tiny boost in FT3/FT4 ratio. The major difference in the higher TSH cohort in controls was that FT4 dropped by a little bit, justifying a TSH from 2.51-4.00.

      But whenever each of these subgroups of healthy controls were turned into cohort averages, we lose sight of individuals’ full range of FT3:FT4 ratios and FT3 levels. Averaging turns unique individual “euthyroid” configurations of FT3, FT4 and TSH into mud.

      As we know, each individual will differ from the other in T4 and T3 at any level of TSH because TSH and FT3 are always on the move during the day, and time of test was not controlled in Gullo. So, alas, one can only use a study to learn a few things, based on the limitations and strengths of the methodologies they used.

  2. Dear Tania, thank you very much for your wonderful article!
    Dr. Hoermann and his team have tried to combine these two paradigms in the article “Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects.” I have a lot of respect for Dr. Hoermann, but it seems to me that this is not possible. TSH certainly plays a role in peripheral conversion, but its main function is to create optimal hormone levels in the pituitary gland. The goal of TSH is to keep the pituitary gland happy )))

    1. Thanks for your comment Vera. Very thoughtful.
      I’ve been following Dr. Hoermann and team’s research publications closely, and they do excellent work.

      It took me a while to understand how Hoermann’s team approach TSH’s role in peripheral conversion. A lot of their work is with patients who don’t have thyroid glands, and in those people, TSH does very little to enhance T4-T3 conversion in the “peripheral” tissues that express DIO1 and DIO2, because their T4 levels need to be higher than normal, and higher T4 downregulates conversion via DIO2.

      Hoermann’s article you’ve identified is the one that talks about the “TSH-T3 disjoint” in LT4 treated patients. The less thyroid tissue you have and the higher LT4 dose you need, the more likely it is that TSH won’t benefit your T4-T3 conversion rate at all, and as TSH rises you’re just likely to be underdosed and hypothyroid.

      However, when people are “untreated” (as some people were in this study by Hoermann), even if a person is very hypothyroid while untreated, the TSH has a very powerful feedforward role in “glandular regulation of T3 production” in the fragment of a thyroid that remains. There is no TSH-T3 disjoint in untreated people.

      Basically, they discovered this profound fact: The HPT axis changes in thyroid loss + therapy. The TSH of an untreated person (with at least some thyroid tissue) behaves very differently from the TSH of a treated thyroid patient, in terms of the ability of that TSH to regulate thyroidal T3 production and thyroidal+peripheral T4-T3 conversion.

      Yes regulating TSH by means of thyroid hormone is a way of making the pituitary happy, if we consider that the pituitary gland often swells (hypertrophy) when forced to secrete way too much TSH. In all my reading of thyroid science, however, I have never heard of a pituitary gland being damaged by increasing thyroid hormone levels enough to suppress TSH.

      1. When you use the term “suppress TSH”, do you mean to lower it from elevated to normal euthyroid levels, or to suppress it to undetectable levels which seems to happen with high LT4 therapy?

      2. Hi murray! Thanks for asking for clarification. It’s true, a lot of people say “suppress TSH” when they just mean “lower TSH.” In my comment when I wrote “I have never heard of a pituitary gland being damaged by increasing thyroid hormone levels enough to suppress TSH.” I meant that I’ve never heard of research talking about high thyroid hormone levels of dosing damaging a pituitary gland and causing central hypothyroidism — failure of the pituitary to secrete TSH. Then once the gland is supposedly damaged in its cells by thyrotoxicosis (if that is even possible), it would not be able to secrete any TSH even if your FT4 is at middle of reference range and so is your FT3. It would be unresponsive to non-excessive dosing. Hypothetically. I just have never heard of this.

  3. I have been reading this series of articles going back almost 2 years and am left with 1 comment, one observation and 1 question. I am an engineer not an MD and am overwhelmed.
    Comment: The discussions are interesting, and the critiques of prior papers very useful, but it comes down to TMI.!! A summary of conclusions w/o all of the discussion would be very helpful.
    Observation: At 1 point you comment that the half life of fT3 is about 12 hours. This is a misunderstanding of the term “half life”. It is 1/2 the time to go from peak to base line. Half life is the time to go half way from the current level to baseline. In Saberi and Utiger’s Fig 5 the 1/2 life is 4 hours.
    Question: My Endo says that rT3 blocks receptors and thus reduces the cellular availability of FT3. You have 3 observations that seem internally inconsistent and probably in contradiction of the Endo’s belief. See: (12/2019) “At normal T3 and T4 concentrations, D1 converts 50% of T4 to T3 and the other 50% of T4 gets converted to Reverse T3. D1 gets strengthened in T4-T3 conversion when T3 levels are higher because it is an enzyme that has a T3 receptor “response element” on it. As T3 rises above mid reference, D1 optimizes T4-T3 conversion: it converts less into Reverse T3, more into T3”. “Deiodinase Type 3 will inactivate FT4 into Reverse T3, while also inactivating circulating FT3 into T2”. (9/2019) “The patient’s Free T4 flowing in blood will always generate T3, RT3, Tetrac and other metabolites — but conversion to RT3 will occur at a higher rate than in healthy normo-thyroid people who are not on L-T4 monotherapy. In other words, nature deals with an isolated excess T4 by converting it to Reverse T3 while depleting T3 hormone
    These 2 observations seem contradictory. Should Part 1 say “more into reverse T3 and less into T3”?
    And then there is this: (8/2020) “The human body doesn’t have to choose between optimized T3 and higher-normal RT3; these two hormones can peacefully coexist. Higher RT3 does not on its own indicate a global rate of T3 loss in cells”.
    Can you clarify the FT4, FT3 and rT3 interactions and effect. Other sources specify a must be less than limit for rT3. Your last comment seems to invalidate such an idea.
    Hoping for an early reply. Respectfully yours, Murray

    1. Dear Murray, I finally have time to attend to your comment. I will do my best to answer in little snippets. I appreciate your engagement with these topics.

      The half life of T3 is a debated topic because its clearance rate changes based on the amount of thyroid hormone (T3+T4 etc) in blood that is occupying binding proteins, being metabolized, and so on. As we know, T3 hormone clears faster in hyperthyroid conditions than in hypothyroid conditions. The article on T3 withdrawal gives a definition of “half life” and more information about how the half life of a given level of T3 shifts based on various contextual factors

    2. The questions about Reverse T3 enter a minefield of internet myths and misundersandings of published research.

      You asked, “My Endo says that rT3 blocks receptors and thus reduces the cellular availability of FT3. You have 3 observations that seem internally inconsistent and probably in contradiction of the Endo’s belief.”

      First: The idea of RT3 blocking thyroid hormone receptors is an internet myth.

      The endo is incorrect. RT3 cannot block (or plug) receptors in the nucleus to which T3 binds, because RT3 has less than 1% of T3’s affinity to receptors. Receptors have levels of “affinity” to bind with different thyroid hormones, and this is determined by complex laboratory experiments on cells. Bolger & Jorgensen did this experiment. In my article, “Deiodinase Type 3 plays the T3-blocking role” I present their findings

      Essentially, RT3 is missing the special iodine “key” to fit into the receptor’s “lock” — the shape of the hormone is not capable of fitting into the receptor because the RT3 hormone molecule has the iodine atom in the wrong location.

    3. Hi again Murray. You were seeing something that looked like a contradiction, and maybe it’s something that I need to clarify.

      Yes I wrote on that page, “As T3 rises above mid reference, D1 optimizes T4-T3 conversion: it converts less into Reverse T3, more into T3” — In fact, to be more specific, as T3 signaling upregulates D1 enzyme. The D1 enzyme is multi-directional and works as a system of priorities:

      1) The D1 enzyme’s main role is to convert RT3 to T2 and to clear sulfated thyroid hormones (T4S, T3S).
      2) Its secondary role is converting T4 into both T3 and RT3.*

      Therefore, as D1 rises in power, it converts T4 more efficiently into T3 and RT3. However, the RT3 concentrations in blood, including any RT3 created by D1 itself, get cleared out more efficiently (because clearing RT3 is D1’s primary role).

      The net result is that we get less RT3 and more T3 out of our T4.

      *Most of my knowledge of D1 comes from Maia et al, 2011’s scientific article on the properties of this D1 enzyme: see

    4. Your final question was about this statement I made: “The human body doesn’t have to choose between optimized T3 and higher-normal RT3; these two hormones can peacefully coexist. Higher RT3 does not on its own indicate a global rate of T3 loss in cells”.

      The deiodinases are not like either-or switches. When one is “on” the other is not “off”. Imagine a waterfall with a river (T4), coming into contact with 3 deiodinases like rocks (cells that express deiodinases) that it crashes onto as it falls down the waterfall. Water is a fluid (like our blood), so you can have some T4 crash onto a D2 rock in the brain and turn into T3, and some T4 crash onto a D1 rock in the kidney and divide into equal parts T3 and RT3 (but if D1 is strong, it will clean up a lot of the RT3 mess it made). Another bunch of T4 water crashes onto a D3 rock in the brain and it turns into RT3.

      Our deiodinases D1, D2 and D3 are all active at the same time in different cells and organs of the body; none of them are ever completely turned off, and they don’t often get into arguments and hurt each other very much. Instead, other substances make each of them stronger and weaker. For example, D3 and D2 cooperate in the brain.

      No, there is no scientific basis for the idea that RT3 has to be less than a certain concentration in blood for us to be healthy and convert well. This is opinion. RT3 is not a toxin. Every day, we have some T4 convert to RT3 and to T3 at the same time.

      On my to-do list is to write an article that explains how we upregulate and downregulate our Dio1, Dio2 and Dio3 genes. Different substances and health conditions make each of them stronger or weaker. The most powerful influences over our deiodinases are T4, T3, TSH in blood, and illness (in sickness, hypoxia and inflammatory cytokines are powerful over them). Other substances can tweak them a bit here and there.

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