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.”
(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.
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.
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.
- 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.
- The thyroid synthesizes both T4 and T3.
- 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.
- Generally, they knew in 1984 what Citterio and team confirmed in 2017: that as TSH rises to stimulate a healthy thyroid, it boosts the T3 side of hormone synthesis.
- If you look at the Human Protein Atlas data sets online, you’ll see the consensus: The thyroid is the main location in our body for tissue RNA for DIO1 and DIO2, so we can expect that we are capable of converting (metabolizing) T4 thyroid hormones to T3 via D1 and D2.
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.
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.
- 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.
- 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.
- 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
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