In 2011, Gullo’s research team published a landmark study in thyroid therapy titled “Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients.”
Gullo and colleagues examined the TSH, FT3 and FT4 levels and the FT3:FT4 ratios of 1,811 thyroidless patients on levothyroxine (LT4) monotherapy and compared them with 3,875 healthy controls.
Gullo’s study shook the foundations of dogma by looking at distortions to thyroid hormone levels within the TSH reference range. It questioned the assumption that “euthyroid” status was achieved merely by normalizing TSH to the range of the thyroid-healthy population. Since it was published in 2011, the article has inspired researchers and patients. I hope to reignite that inspiration.
Gullo’s team found several inequities between the two populations at the same TSH levels:
- The healthy controls’ relative position of FT3 and FT4 within their reference ranges was inverted by thyroid loss and LT4 monotherapy.
- The FT3 hormone, after being lowered in treated people, behaved abnormally in yet another way: FT3 fell further as TSH rose within reference range, while healthy subjects’ average FT3 did not fall as TSH rose within reference.
- The separation between the lower FT3 and higher FT4 in the treated population was a significant contrast with controls. As a result of this relative FT3 shortfall per unit of FT4, the average FT3:FT4 ratio in treated people fell significantly lower, with 29.6% of LT4-treated patients below the ratio’s reference range in controls.
- Women and older persons were more likely to have the lower FT3 levels and FT3:FT4 ratios, but the absolute FT3 loss was far more significant in the LT4-treated group.
In this post, I review and critique a set of FT3 and FT4 graphs by Gullo et al, 2011. They show general trends in average FT3 and FT4 relationships in blood at various levels of normal TSH.
I provide several ways of re-visualizing these graphs’ data so that we can see them enhanced by color coding and overlaid on top of each other.
Gullo’s original graphs’ Y-axes (vertical axis) didn’t show the full reference ranges, which means there’s a vertical distortion. Therefore, I provide visual adjustments that show the hormones’ relative positions within their ranges.
I also provide further commentary in light of other scientific research. What is the implication for health throughout the body, given that T3 hormone plays the vast majority of essential signaling, while T4 and TSH hormones have very different effects on the body? Why does the healthy HPT axis appear to maintain average circulating FT3 levels as TSH rises within range, and why can’t treated patients maintain their FT3 as TSH rises in range? Finally, what does this inequity mean for our treatment guidelines and testing policies?
Copyright fair dealing note
Step 1. Gullo’s original graphs
This pair of graphs separate FT4 trendlines in one graph from FT3 trendlines in another graph.
Both graphs have the same horizontal X axis — TSH from 1 to 10, on a logarithmic scale.
In the two original graphs, notice that:
- dotted lines represent treated patients, with higher FT4 than controls.
- bold lines represent euthyroid controls, with higher FT3 than treated patients.
Step 2. Gullo’s graphs overlaid, hormones in color
If one were to overlay the graphs as-is and turn FT3 trendlines pink, FT4 trendlines teal blue-green, you would get this image:
This image drives home the point that the TSH reference range 0.4 to 4.0 is the same, but the hormone levels differ considerably.
Step 3. Gullo’s graphs with full reference ranges adjusted to midpoints
Next, there’s a visual distortion that needs to be corrected. The Y axes (vertical) are not showing the full reference ranges.
- Both the top and bottom of the FT4 range is missing (9.0 – 20.6 pmol/L).
- The FT3 reference range is shortened at its top (2.9 – 6.0 pmol/L)
In addition, the center of the graphs are not adjusted to the mathematical mid-points of each of the reference ranges.
- The midpoint of the FT4 range is 14.8 pmol/L
- The midpoint of the FT3 range is 4.45 pmol/L
Now that full ranges are shown, and midpoints of the two reference ranges are aligned across the horizontal gray line, the FT4 trendlines in teal are positioned much higher in relationship to the two pink FT3 trendlines.
Now the graphs visually align with Gullo’s findings regarding the FT3:FT4 ratios in treated vs. untreated individuals.
The scales of injustice: Illustration
The injustice in the illustration above is that the two scales are evenly balanced in TSH concentration but they are very unequal in hormone concentrations of FT3 and FT4. Even if there are fewer pmol/L of FT3 in circulation, signaling potency of FT3 and its active T2 metabolite makes each pmol/L of FT3 worth many times the weight of a pmol/L of FT4. The person with the healthy thyroid is richer.
The injustice potentially becomes a sex-specific prejudice by means of research neglect of women’s health outcomes. Most of the FT3-deficient persons in Gullo’s study were women. “The percentage of athyreotic patients with FT3 serum levels lower than the normal range was 8.6% in males and 16.4% in females.”
For many decades, scientists have neglected to study the health risks of the population rendered FT3 deficient by thyroid disability and therapy, so we are still unable to determine whether women’s health suffers more than men at these lower levels of FT3 after complete thyroid tissue loss.
Data visualization critique
Of course, these two trendline graphs still have handicaps in communicating the true shape of the data.
- Their strength is that they oversimplify, making the “bare bones” of a complex system stand out boldly.
- Their weakness is also that they oversimplify, focusing only on the linear trends among statistical averages, failing to characterize the diversity and central tendency of data within the populations sampled.
Averages vs. distributions
By means of their focus on averages, the simple trendline graphs fail to identify the extent to which outliers exist with far higher FT4 levels beyond reference or far lower FT3 levels beyond these hormones’ reference ranges.
Fortunately, Gullo’s additional graphs revealed the distribution of FT4 and FT3 within LT4-treated populations, with a shaded area representing the controls’ range and a dotted line showing the mean among healthy controls.
Gullo’s research revealed that 29.3% of people with no thyroid function who are forced to live on T4 supply alone obtain a FT3:FT4 ratio below the reference range. In addition, 15.2% of this population is forced to suffer a FT3 below reference range merely for the sake of TSH normalization as a policy target.
Gullo’s study did not provide distribution graphs for healthy subjects alongside the LT4-treated patients’ distribution graphs, above.
Fortunately, Ganslmeier et al, 2014, provided a set of graphs using some of the most carefully-vetted data sets yet published. They even screened for mild thyroid failure using thyroid ultrasound and TRAb (anti-TSHR) antibody tests.
Notice that in the healthy FT3 distribution, two bars at the mid-point of range almost achieve 25%. This means that almost 50% of the healthy population attains mid-range FT3.
In the TSH-driven healthy controls, both low-normal and high-normal FT3 is rare. This data pattern echoes the FT3’s role as a metabolic target, in contrast with TSH, which is a metabolic tool, only one of several means of adjusting and maintaining euthyroid FT3 levels for the individual.
Separate hormone trends vs. individuals’ FT3:FT4 ratios
By isolating the two hormones’ averages, the simple trendline graphs do not express the FT3:FT4 ratios found within individuals, such as people with an extremely low ratio (top-of-range FT4 and a mid-range FT3, or mid-range FT4 with a bottom-of-range FT3).
Since the human body engages in continual 2-way transport of hormones in and out of cells where T4-T3 metabolism occurs, the ratio is a good representation of global T4-T3 conversion efficiency as well as thyroidal supply in healthy controls. In the thyroidless person who has been barred from access to both thyroidal and pharmaceutical T3 supply, the ratio purely represents metabolic efficiency.
Fortunately, Gullo provided a distribution graph for the LT4-treated patients’ ratios. They show a larger percentage of the treated population below reference in their ratio (29.7%) than for the FT3 levels below reference (15.2%):
Within the TSH reference range vs. below it
Populations that depend on TSH receptor signaling to stimulate 100% of their T3 and T4 hormone supply are different from populations whose TSHR signaling stimulates 0% of their thyroid hormone supply.
In the latter population, bloodstream FT3 and FT4 ratios that are not generated by TSHR signaling in a healthy thyroid gland will interfere in the natural feedback loop and imbalance TSH response, creating a TSH-T3 disjoint. (Hoermann et al, 2013; See “The TSH-T3 disjoint in thyroid therapy“).
The higher levels of FT4 found in T4 monotherapy have a more powerful TSH-suppressive effect, partly due to tissue-specific T4-T3 conversion rates in the hypothalamus and pituitary. This renders TSH secretion rates insensitive to lower FT3 levels in blood.
By focusing only on hormones within the TSH reference range, the trendline graphs failed to express what happened to FT3 levels as TSH response fell below the statistical parameters of the healthy TSH-coregulated population.
Gullo’s study did not examine these hormone configurations at all, leaving it as a fruitful topic of study for other researchers characterizing the untreated HPT axis vs. the LT4-treated HPT axis.
More recent research not only confirmed the trendlines within the TSH reference range, but demonstrated that lower-than-mean FT3 levels continue to be found in other populations of LT4-treated people, even at the extreme of TSH suppression.
To the left of the pink box in Larisch’s scatterplot, it is difficult to maintain that patients with low or suppressed TSH could suffer from thyrotoxicosis while they have a low or low-normal FT3. Such FT3 levels, which are largely responsible for genomic signaling in the receptor, are inconsistent with both thyroxicosis and euthyroidism. In fact, patients with lower FT3 are far more likely to suffer from the very opposite condition — hypothyroidism — in their extrapituitary tissues, which conflicts with their low or suppressed TSH and higher-than-average FT4. When hormone signals conflict, the most powerful signaling hormone, FT3, has the loudest voice when determining tissue thyroid status.
To confirm patients’ suffering at lower FT3 levels, one must go beyond Gullo’s study. Larisch et al, 2018 and Hoermann et al, 2019 have now demonstrated that the likelihood of hypothyroid symptoms increases as FT3 levels drop below the mid-range healthy FT3 population mean, even if TSH concentrations drop and FT4 rises.
These populations were carefully screened to be free from non-thyroidal illness, so neither their symptoms nor their FT3 levels could be blamed on non-thyroidal illness. They were both induced by hormone dosing and its inefficient metabolism in some patients, because adjustment in hormone levels removed the symptoms.
To what degree do FT3 and FT4 in blood represent global hormone supply, transport and metabolism?
T4-T3 and T3-3,5-T2 conversion occurs within cells expressing D1 or D2 enzymes, and T4-RT3 and T3-3,3-T2 conversion occurs within cells expressing D3 or D1 enzymes.
These three enzymes are expressed at different rates in different tissues. Thyroid hormone transport and metabolic activities occur at different rates within each tissue to customize the bloodstream supply to local needs.
Science informs us that each tissue and organ converts T4 to T3 at a different rate, and that biochemistry can’t tell us how much T3 only the brain is getting into its thyroid hormone receptors, or how much T3 only the liver is getting.
Nevertheless, since thyroid hormone transport in and out of cells is a 2-way exchange that continually occurs throughout the body over time, the FT3 and FT4 in the bloodstream is a representation of the body’s global metabolic rate, as well as thyroidal (and/or pharmaceutical) supply.
Biochemical measurements of hormone concentrations are a useful estimate of overall thyroid hormone metabolic efficiency. Unless a scientist is performing a study of one specific organ or tissue’s metabolic rate and T3 receptor occupancy, one doesn’t need to estimate tissue-specific T3 supply and metabolic rates.
Bloodstream levels reflect metabolic rates because the same transporters that carry T4 and T3 into a cell are capable of transporting them out again. A variety of transporters can serve a single tissue, like the liver. The net quantity of hormone influx will equal the efflux. Some of the T4 that enters cells will also exit those cells as T4 (unconverted to T3), and some T3 will exit the cell as T3 (without being converted to a form of T2). Cells will donate much of their hormone metabolites RT3, T3, T2 and T1 to the bloodstream, and yet any thyroid hormone can be re-used by many cells until it is metabolized or excreted.
In particular, Free T3 consists of both the product of global T4-T3 conversion rates and any T3 supply from the thyroid or pharmaceuticals. In persons who cannot secrete T3 from a thyroid and are only dosed with synthetic T4 hormone, 100% of their T3 quantity is dependent on global T4-T3 metabolism rate, while subtracting global T3 losses due to T3 metabolism and clearance rate.
Therefore, the FT3:FT4 ratio can be used as a biomarker for “global deiodinase efficiency” (D1 + D2 + D3) (Dietrich et al, 2016). This ratio can be interpreted in light of a particular ratio and rate of supply from a thyroid and/or pharmaceuticals.
According to Pilo et al, 1990, in 14 healthy people whose thyroids were stimulated by a TSH between 1.0 and 2.0, an average of 27.3% T4 converted to T3 every day. But this average rate varied widely from person to person. The lowest global T4-T3 conversion rate was 16.9% and the highest T4-T3 conversion rate was 42.9%.
Therefore, in healthy people, thyroidal T3 secretion rates, and the thyroid’s T3:T4 secretion ratio, attempts to adjust to make up for shortfall in the body’s global T4-T3 conversion rates, and this obtains an appropriate level of FT3 and FT4 in bloodstream.
But in T4-dosed people without thyroids, there is no way to make up for a global T4-T3 conversion rate shortfall.
What potential harm? Imbalanced T3 and T4 hormone signaling.
Both T4 and T3 have signaling activity in the human body. However, each hormone has a different signaling pathway and a different affinity or potency at various thyroid hormone receptors.
A shortfall in FT3 supply and excess of FT4 will have implications for metabolism and signaling.
- FT3 is necessary to top up local T4-T3 conversion rate in any tissues that do not convert T4 as efficiently.
- FT3 is also necessary in tissues that may have a higher rate of T3 than T4 influx via transporters and may require a higher quantity of T3 receptor occupancy than others.
T3 hormone performs the vast majority of signaling in the three known locations for thyroid hormone receptors 1) in the nucleus, 2) in mitochondria, and 3) at the integrin αvβ3 receptor on the cell membrane.
For advanced readers: click to read more
Why doesn’t TSH receptor signaling have a similar effect in both populations?
TSH is not just a response to thyroid hormone, but is itself a signaling hormone. It sends signals at its own TSH-receptor on the cell membrane.
People with healthy thyroids get a lot more out of their TSH-receptor signal than people with damaged or missing thyroids. Healthy thyroids also drive and maintain FT3 and FT4 supply by means of more than just their TSH concentrations, since healthy thyroid function depends on sufficient iodine, iron, and other substances.
When the thyroid gland is in good health, benign TSH signaling does more than just enhance the rate of T4 and T3 synthesis within living thyroid tissue. It also shifts the ratio of thyroid hormone synthesis to enhance the FT3:FT4 ratio in blood. As TSH rises within reference, thyroidal T3 synthesis will be stimulated relatively more than T4 synthesis (See review: “T3 is not always converted from T4: De novo T3 synthesis.”), unless TSH is blocked at its receptor by TSH-receptor blocking antibodies (TBAb).
TSH receptors are expressed not only in the thyroid gland, but in tissues throughout the body, where their signal can upregulate D1 and D2 enzymes. A higher TSH will enhance T4-T3 conversion rates 1) within the thyroid and 2) in tissues beyond the thyroid.
For advanced readers: click to read more
Why the steady FT3 in health?
In thyroid health, the thyroid gland’s T4 and T3 secretion rate and ratio is nature’s method of counterbalancing the TSH’s stimulation of the metabolic rate of T4-T3 conversion in cells throughout the body.
The two counterbalancing systems maintain a homeostatic equilibrium in blood levels of FT3 and FT4 that support healthy tissue-level T3 and T4 hormone signaling (See “Relational Stability, part 4: The new thyroid paradigm“).
The ultimate metabolic target of this system is to maintain the individual’s circulating FT3 supply from day to day, week to week, and month to month (Abdalla & Bianco, 2014), in relationship to a fluctuating FT4 and TSH that respond to the current metabolic demand in order to adjust FT3.
Average trendlines do not represent individuals, and thyroid therapy must be individualized.
In thyroid hormone metabolism and signaling, “optimal” FT3 and FT4 concentrations in blood are highly individualized.
The healthy thyroid metabolism keeps FT3’s circadian rhythm fluctuating narrowly within that person’s uniquely optimized area inside the wider reference range. (See our research review “Thyroid T3 secretion compensates for T4-T3 conversion“)
Thyroid hormone concentrations must maintain a state of metabolic homeostasis between hormone supply, metabolism and signaling, given each person’s unique metabolic strengths and handicaps, and their body’s current metabolic demands.
In thyroid health, each individual’s optimal FT3 and FT4 is located at a uniquely narrow band within reference range. (See our review “Individual thyroid ranges are far narrower than lab ranges.”)
In health, this FT3 and FT4 homeostatic setpoint is achieved by TSH-receptor stimulation of a thyroid gland and the person’s global metabolic rate of T4-T3 conversion across all tissues.
But in thyroid-disabled people on therapy, the FT3 and FT4 are not primarily influenced by TSH-receptor stimulation and thyroidal secretion. Instead, they are powerfully manipulated by dosing and deiodinases (D1, D2, D3) that convert hormones. TSH has a very limited influence on secretion and metabolism in those with limited thyroid function, and therefore TSH negative feedback response is an insufficient biomarker of sufficient thyroid hormone signaling.
Individualization of FT3 and FT4 concentrations continues to exist in thyroid therapy. Moreover, in therapy, the diversity of “optimal” of FT3 and FT4 levels is more extreme due to the severity of overlapping thyroidal and metabolic disabilities for which FT3 must compensate, and FT4 and TSH must adjust to accommodate.
The fact that each individual has “optimal” levels does not mean that measuring FT3 and FT4 hormones is pointless in therapy. It means the opposite. It would be harmful for a person who needs FT3 near the top of reference to suffer with a FT3 level below mid-reference. In people who convert T4 poorly, more FT3 will be needed per unit of FT4 to make up for poorer T4-T3 conversion rates in tissues. Over time, blood measurements are an objective guide that helps one to interpret symptoms and signs of imbalance, as well as alleviate them.
Correlations between symptoms and thyroid hormone levels are strong, even before treatment begins, while TSH is elevated. For example, Meier et al in 2003 performed a study that correlated thyroid symptoms with FT3, FT4 and TSH, and found
“In contrast to the good correlations with both circulating thyroid hormones, we found no correlation or only weak correlations with serum TSH.”
In the context of standard LT4 monotherapy, most people, even the thyroidless, have the metabolic strength to achieve optimal FT3 levels — but only if the LT4 dose is raised until FT3 levels remove symptoms and measurable tissue biomarkers of thyroid hormone signaling (Ito et al, 2012-2019; Hoermann et al, 2013-2019; Larisch et al, 2018)
However, a strategy of LT4 dose escalation will not work for up to 33% of individuals after a thyroidectomy, whose FT3 remains below reference range even at the point of TSH suppression:
“Even when escalating LT4 dose as a treatment strategy to suppress TSH levels below its reference range during early follow-up of the carcinoma patients, FT3 concentrations remained below the lower part of its reference range in one third of the presentations.”(Larisch et al, 2018)
Note: Despite this metabolic handicap in 1/3 of the patients studied, the scatterplot graph by Larisch et al, 2018, shown above, reveals FT3 levels within reference. It is likely, therefore, that for these metabolically handicapped individuals, the compassionate physicians raised their LT4 dose further past the point of TSH suppression to raise their FT3 into reference range, and to alleviate symptoms.
This extreme metabolic diversity is why effective LT4 thyroid hormone therapy must be adapted to the individual, not only in terms of permitting a higher dosage and FT4 levels in some people (if their T4-dominant signaling at the integrin receptor does not cause health problems), but in terms of permitting TSH response to fall lower for the sake of global FT3 and FT4 metabolism and T3 signaling. (Midgley et al, 2015; Hoermann et al, 2013, 2017, 2019)
For the patients who remain symptomatic or ill with FT3 levels below the mid-range population mean, and especially those who remain below range in FT3 even at a suppressed TSH and elevated FT4 level, T4-T3 combination therapy is the logical metabolic solution (Hoermann et al, 2018, 2019).
Despite the failures in research methods in T3-T4 combination therapy, no studies have shown that the incorporation of T3 is any more dangerous than T4 monotherapy as long as doses are reasonable.
Overall, the methodologically faulty T3-T4 combination therapy trials demonstrate that combination therapy was equally effective (on average) compared to LT4 monotherapy when both were just as poorly optimized. In these studies, even LT4 monotherapy was not optimized, being blindly normalized only to the TSH rather than to FT3 levels. These trials averaged results from diverse thyroid patients, and their results were not representative of the poorest T4 converters, those who lack thyroid function and suffer from thyroid metabolism handicaps.
For poor converters of LT4 monotherapy (Midgley et al, 2015), combination T3-T4 therapy at a dosing ratio that suits the individual is the ethical, compassionate option.
Moreover, optimization of T3 and T4 signaling is an absolute necessity to protect health of all organs and tissues for the remainder of the person’s life.
In the context of flexible T3-T4 combination therapy, virtually any combination of FT3 and FT4 concentrations becomes possible. To prevent thyroid hormone excess at a global level, FT4 intake will need to drop to accommodate rising FT3 levels from T3-containing pharmaceuticals. The lower the FT4 falls, the more FT3 in blood is necessary to compensate for the lower T4-T3 conversion rate. Overall, as a patient’s thyroid hormone therapy is adjusted to their individual needs, their suffering or improvement can be objectively correlated with their changing FT3 and FT4 levels and ratios over time, when a physician understands the various factors involved in metabolism and signaling. (See “Flexible-Ratio T3, T4, and NDT Combination Thyroid Therapy“)
Gullo’s descriptive study was significant enough to be reviewed in sections of the 2012 and 2014 American Thyroid Association (ATA) guidelines for treatment of hypothyroidism (Garber et al, 2012; Jonklaas et al, 2014). Both sets of writers attempted to throw a wet blanket on the revolutionary implications.
The 2014 ATA guidelines by Jonklaas admitted decades of neglect and ignorance within the endocrinology community regarding the clinical significance of this shift, claiming that the health outcomes were as yet “unknown.”
Instead of admitting that the FT3 and FT4 levels and ratios were extreme shifts in levels of the most powerful signaling hormone, Jonklaas’ ATA 2014 guidelines called them mere “perturbations” of FT3 because they occurred within the reference range. They also shrugged at FT3 levels that were “mildly low,” when most studies of nonthyroidal illness have been honest enough to acknowledge even “mildly low” T3 levels as major drivers of mortality and morbidity (For example, see “Ataoglu: Low T3 in critical illness is deadly, and adding high T4 is worse.“)
These guidelines used verbal rhetoric to justify and minimize decades of scientific neglect and ignorance of the human cost of T3 deficits in the LT4-treated population.
It has always been thyroid endocrinologists’ professional mandate to answer such questions that are essential to the health of thyroid-disabled people, instead of presuming that human metabolism will always convert “enough” T4 to T3 in cells throughout the body.
Worldwide, potentially millions of patients suffer poor thyroid hormone metabolism. Policy-mandated T3-less therapy, merely normalized to TSH and not optimized, combines with general scientific complacency toward investigating their supposedly “unknown” health outcomes at lower-than average FT3 levels.
But the clinical significance of insufficient T3 signaling in tissues has not been unknown to patients or compassionate doctors. Symptoms that agree with FT3 and FT4 levels are far more clinically significant than a mere “surrogate” endpoint like TSH in isolation. Health outcomes in T3-aspects of chronic illnesses are strong endpoints that TSH cannot usurp as a mere surrogate.
By making only the TSH’s negative feedback loop into the sole target and the only surrogate endpoint of therapy, policy has ignored the TSH’s broken feedforward loop on T3 secretion that can make up for shortfalls in T4-T3 conversion. The potency of the TSH’s feedforward loop in a state of thyroid gland health is the main reason that a negative feedback loop exists; the brakes are only necessary when the gas pedal is functional. Thyroid therapy policy today is like a car being driven by brakes. Health can’t be driven by a negative feedback loop.
In 2014, the ATA’s guideline writers attempted to straitjacket researchers from pursuing the argument stated in Gullo’s 2011 title. They tried to make reasonable scientific questioning of the concept of TSH-based euthyroid status seem ridiculous and unethical (See “2014 ATA therapy guidelines: 5. Research“). Instead, the very idea of misapplying the untreated population’s TSH-based euthyroid status to the thyroid-damaged population ought to be ridiculous and unethical. The FT3 and FT4 inequity per unit of TSH between the two populations renders “normal” TSH an unfair judge of euthyroid T3 signaling beyond pituitary and hypothalamus tissues.
Japanese scientists Ito and team saw this FT3 inequity result in clinically-significant symptoms and had the courage to critique the ATA’s TSH-targeting policy directly in their discussion section (See “Japanese thyroid scientists examine symptoms in relation to FT3 and TSH“).
The major hindrances to thyroid hormone health during therapy consist of inappropriate apathy, inappropriate fear, prejudice, and reluctance. They are
- Inappropriate apathy toward mildly lowered FT3 and signs and symptoms of lower T3 signaling in tissues that are less efficient at local T4-T3 conversion,
- Inappropriate reluctance to measure and adjust the most vital hormone’s concentrations to alleviate symptoms and improve health,
- Fear of mildly higher FT3 levels and intermittent, short-term post-dose peaks that drives unreasonable prejudice against T3 hormone pharmaceuticals, when research shows they can fill a T3 deficit without causing measurable harm to health, and
- Reluctance to perform research that associates FT3 levels and FT3:FT4 ratios with long term health outcomes in the most vulnerable thyroid-disabled, treated populations.
A few groups of scientists like those led by Gullo, Hoermann, and Ito have led the way for cardiologists, kidney, lung, and liver specialists to follow when they are ready to study treated thyroid patients. We’re ready for them and waiting to be recruited and heard.