An example of confusion about Free T3: Free T4 ratios

There’s a lot of confusion out there about Free T3: Free T4 ratios in bloodstream.

Part of the confusion is about how these ratios are expressed in numbers and phrases. Should you express this ratio in blood as 1:4, 4:1 or 0.25, or 4.00?

A second confusion may lead to a more substantial and harmful mistake. It is the idea that a scientific description is a prescription. Narrow descriptive findings in research, such as average FT3:FT4 ratios in a healthy-thyroid population, can easily be misapplied as prescriptive targets for thyroid therapy.

But researchers understand the full range of diversity in their own study population. They would not expect their statistical average, let’s say a FT3:FT4 ratio of 0.32 mol/mol, to immediately become a therapy target for the individual in their population who had the highest ratio of 0.40 mol/mol.

In a large mixed population, there are bound to be both healthy AND unhealthy individuals with a high ratio. The same high ratio can be anchored in a lower or higher FT4, so one must establish cause and effect before blaming the problem on the ratio and trying to fix it.

A third confusion (truly a mistake) is related to description versus prescription, but with a twist. It’s the mistake misapplying one population’s descriptive results to a very different population as a prescription.

It is a gross mistake to believe that an average 0.24 or 0.32 FT3:FT4 ratio in a study on one population (people on LT4 therapy, or healthy untreated controls) can be transferred to a very different population (people on desiccated thyroid therapy) as a prescription.

As populations lose thyroid function, their average ratios fall per unit of TSH, but not everyone experiences the same degree of metabolic loss. Inducing a higher than average ratio without elevating TSH may be therapeutic to the most severely disabled individuals.

Recently, all three of these mistakes combined to create a perfect storm of numeric confusion and potential harm to a patient.

In this post, I give an example of a physician’s confusion reported in a thyroid patients support group, and I explain two possible sources of the ratio misquoted and misapplied by the physician.

The patient’s report and confusion

In our patients’ private support group recently, a patient posted a message beginning “Help! I’m confused.”

She said that her general practitioner told her that

“the ratio between free T4 and free T3 is supposed to be 4:1.”


In one of my comments under the post, I mentioned that maybe the doctor was confused by the 4.2 to 1 T4 to T3 ratio contained in desiccated thyroid (NDT / DTE) tablets, since that’s the only ratio close to 4:1 in thyroid science, and she was dosing NDT.

Alternatively, it is entirely possible that she misheard or misunderstood her physician, but let’s take her word for it for now.

This way of expressing a ratio in blood certainly was confusing, because dose ratios and blood ratios have different conventions in thyroid science publications:

  • Dose: A pharmaceutical LT4-LT3 combination dose ratio is expressed with a colon between two numbers, such as 14:1, meaning 14 micrograms of levothyroxine (LT4) per 1 microgram of liothyronine (LT3). For example, see dose ratios discussed in “Mimicry: The idol of T3-T4 combo therapy 2004-2014
  • Blood: A ratio of FT3:FT4 or T3:T4 concentrations divides the first hormone’s result by the second to obtain a mathematical quotient, such as 0.32 (if dividing a FT3 of 5.00 by an FT4 of 15.5.) For example, see ratios discussed in “Normal FT3:FT4 thyroid hormone ratios in large populations

After paraphrasing her doctor’s statement, she mentioned that on 90 mg of desiccated thyroid, she has a ratio of less than 3:1 in blood, derived from FT4 12 (range 9-19) and FT3 5.6 (ranges 2.6-5.8). Another physician said “it’s fine,” so she wanted to know what the truth was.

In the responses under this post, many others, like me, had never seen ratios in blood expressed in the format of “4:1,” and there were more questions than answers.

Eventually, I discovered where this 4:1 ratio might have come from, and why it was a mistake to communicate this ratio this way, and that it was taken out of context.

Where could the mistaken 4:1 ratio come from?

I’m not entirely sure, but I have two working theories.

I’m going to presume something quite flattering about this doctor and their colleagues. Perhaps they read thyroid science, or perhaps they interact in forums where people discuss thyroid science.

Possible source #1: Roef’s average FT3:FT4 ratios in ng/dL

In 2014, Roef et al included ratio calculations on a large-scale study. It was a very specific population.

“restricted to 2315 subjects (1138 women and 1177 men), not using thyroid medication, not having anti-TPO levels above clinical cutoff values or TSH levels outside the reference range (0.27–4.2 mU/L).”

(Roef et al, 2014)
  • Roef, G. L., Rietzschel, E. R., Van Daele, C. M., & Taes, Y. E. (2014). Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid : Official Journal of the American Thyroid Association, 24(2), 223.

The table of results included these values:

Women (n=1138)Men (n=1177)
fT4 (ng/dL)1.25 (1.15–1.35)1.34 (1.23–1.44)
fT3 (pg/dL)300 (280–320)338 (310–3.60)
fT3-to-fT4 ratio0.24 (0.22–0.26)0.25 (0.23–0.28)
(Roef et al, 2014, from Table 1)

The ratio was calculated by converting FT3 into ng/dL (the same unit as fT4) by dividing the FT3 by 1000 to yield 0.3 for the women, 0.338 for the men. The FT3 in ng/dL were then divided by their respective FT4 values for each sex.

Data are given as medians (first–third quartiles) because of non-Gaussian distribution. 

  • The first quartile Q1 is the 25th percentile
  • The second quartile Q2 is the 50th percentile
  • The third quartile Q3 is the 75th percentile

Therefore, the central part of the distribution was quite narrow for women and a little wider for men.

The problem with using this 0.24 or 0.25 ratio is that it does not map onto the patient’s results in pmol/L.

T3 has a different molecular weight than T4 because it has one less iodine atom, and so the conversion factors are different when you convert them to pmol/L.

Roef and colleagues gave the conversion factors under Table 1:

“Conversion factor for fT3 from pg/dL to pmol/L and for TT3 from ng/dL to nmol/L is ×0.0154;

conversion factor for fT4 from ng/dL to pmol/L is ×12.87.

(Roef et al, 2014)

The conversion factors to SI units can also be verified in the AMA SI unit conversion calculator table.

Important: The conversion must be applied to the FT3 and FT4 lab results before one is divided by the other.

To obtain a true “average ratio” for the population, we’d need to go back to their raw data and convert each lab result, and obtain a ratio for each patient in “molar” units (mol/mol). All we have access to in this table is the population’s average concentration for each separate hormone. Nevertheless, if the raw data set was not skewed or too widely distributed, the results will probably be very close.

Converting these averages to pmol/L and then dividing the one by the other yields the following “ratio of averages”:

  • Women FT3 4.62 pmol/L, FT4 16.09 pmol/L = FT3:FT4 ratio of 0.287
  • Men FT3 5.21 pmol/L, FT4 17.25 pmol/L, = FT3:FT4 ratio of 0.30

(If you divide the FT4 by the FT3 to invert the ratio, you get 3.48 for women and 3.31 for men, but this is not advisable because most ratios now use FT3 as numerator, FT4 as denominator.)

Therefore, after converting to pmol/L properly, it will no longer be a 0.25 ratio calculated with ng/dl (nor will it be an inverted ratio awkwardly expressed as a dose ratio of 4:1. It is closer to 3:1 in mol/mol).

The larger problems are that Roef and team 1) were not establishing a therapy target, 2) nor were they analyzing the data of patients with thyroid disabilities, 3) nor were they studying ratios artificially achieved by T4 and T3 dosing.

They were studying people whose ratios were created partly by TSH stimulation of a thyroid gland, partly by peripheral metabolism of T4 to T3 and of T3 to other non-T3 metabolites.

The TSH must be considered as a separate variable in this study, even though TSH was not as statistically significant as the FT3:FT4 ratio. TSH receptors are also located in some cardiovascular tissues and in some liver cells where a higher level of signaling may worsen preexisting pathologies.

In some people, TSH may rise at the same time as the ratio rises (a higher ratio may be induced by a lower FT4), while in other people TSH may reduce (if the higher ratio is primarily caused by an isolated rise in FT3).

The pituitary and hypothalamus tissues that regulate TSH secretion metabolize FT4 and FT3 differently than the liver, heart, or blood vessels. Different tissues “interpret” thyroid hormone ratios differently, and various illnesses can distort local T4 and T3 metabolism.

Now that our FT3 and FT4 assay technologies are precise enough as research tools (despite their shortcomings), and now that researchers are creating free hormone ratios, not total hormone ratios, they are discovering that the free thyroid hormone ratio is often more clinically significant than TSH.

Their conclusion identified an association, but we should all know that correlation is not causation:

Conclusion: In healthy euthyroid middle-aged men and women, higher fT3 levels, lower fT4 levels, and thus a higher fT3-to-fT4 ratio are consistently associated with various markers of unfavorable metabolic profile and cardiovascular risk.

(Roef et al, 2014)

Metabolic syndrome and cardiovascular risk could be an indirect cause of the ratio mediated by TSH and a thyroid gland, not an effect of the ratio.

The health problem of metabolic syndrome may raise the TSH and/or lower the FT4.

Although the researchers saw no sign of iodine deficiency or thyroid failure, the body’s normal response to a lower FT4 would be similar to iodine deficiency or early thyroid failure. The rise in TSH will shift the T3:T4 secretion ratio toward T3 to elevate circulating FT3. Circulating T3 can compensate for a lower quantity of FT4 entering cells and becoming T3 in cells.

However, we don’t know if TSH rose first, or if T4 fell and caused TSH to rise. We don’t yet know the first cause or the effect. Let’s put speculation aside for now.

At least we know that the ratio shift is a strong sign that something unusual is happening, and their ratio shift is a stronger signal than TSH.

The authors responsibly cautioned,

“An important limitation consists in the cross-sectional design, which does not allow us to make causal inferences from the observed associations.

(Roef et al, 2014)

Fixing everyone’s high FT3:FT4 ratios to be exactly 0.25 (if measured in ng/dL) or 0.30 (if measured in pmol/L) is not being proposed as a solution.

A clinical trial of a hypothetical “fix” may need to be performed before a higher than normal FT3:FT4 ratio could be confirmed as a cause, rather than effect, of metabolic syndrome and an elevated TSH.

If the ratio is the cause of poor health, how would you propose therapeutically lowering their ratio?

  • To lower their FT3, you could dose them with PTU (anti-thyroid meds) to reduce their T4-T3 conversion rate, or
  • To raise their FT4, you could dose them with a little LT4 hormone and that could bring down their TSH as well.
  • To bring down TSH, one could use a wide variety of TSH-suppressing substances (See Haugen’s 2009 list of drugs that suppress TSH).

But it would be quite radical in our current context to dose these people despite the fact that they are neither hyper- nor hypothyroid in terms of their TSH and FT4.

Possible Source #2, Midgley’s poor converter threshold in pmol/L, 0.25

There’s another potential fit with the 4:1 ratio if you perform mathematical operations on Midgley et al’s 2015 journal article:

  • Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015). Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. Endocrine Connections, 4(4), 196–205.

Nowhere in this article does it talk about a 4:1 ratio or even a 0.25 ratio, but I derived it from the article’s data by using the very same desktop computer program they used to obtain their results.

Midgley and team had set a threshold for the “poor converter ” category at a deiodinase activity of “<23 nmol/s.” This is a measurement derived by entering FT3 and FT4 lab results into the SPINA-Thyr desktop program and obtaining the result for global deiodinase efficiency (GD).

In SPINA-Thyr, the Thyroid carcinoma averages of FT3 5 pmol/L and FT4 20.2 pmol/L obtain a deiodinase activity (GD) of 22.89 nmol/s, which is close to 23 nmol/s. (See our walkthrough at “Analyze thyroid lab results using SPINA-Thyr“)

Therefore, Midgley’s benchmark for “poor converters” could also be expressed by an FT3 of 5.0 and an FT4 of 20.

By dividing an FT3 of 5 by an FT4 of 20, one obtains a ratio of 0.25.

If this is the source, someone, somewhere may have converted Midgley’s GD 23 nmol/s benchmark to a ratio of 0.25, and then inverted it by dividing the opposite direction to obtain a ratio of 4.00, and then mistakenly expressed it as a dose ratio of 4:1.

Admittedly, it’s a bit far-fetched to derive the mistaken 4:1 from this article because it involves several steps in recalculation, but you never know where mistakes can come from.

On the other hand, the therapeutic significance of the FT3:FT4 ratio of <0.25 as a meaningful threshold for “poor converter” status on LT4 monotherapy may have travelled through online discussion forums to get to this physician.

But here’s the catch: While Midgley’s article was studying treated patients, it was not assessing a health risk or establishing a therapy target, nor was it analyzing the data of patients on desiccated thyroid.

The article did not claim that people with a GD of less than or more than 23 (FT3:FT4 ratio of 0.25) will be more likely to suffer symptoms of hypothyroidism or hyperthyroidism or have adverse health outcomes while on LT4 therapy — or any other therapy.

This ratio is simply describing the efficiency of thyroid hormone metabolism.

The threshold of GD <23 nmol/s (FT3: FT4 ratio <0.25 mol/mol) was also associated with loss of thyroid volume. In a previous study by the same research team, they found that the global T4-T3 conversion rate was far more likely to be impaired in people with less than 5 mL of thyroid tissue, whether their low thyroid volume was due to a total thyroidectomy or autoimmune thyroiditis (loss of thyroid volume from antibody attack is called atrophic thyroiditis).

We each have a different degree of metabolic inefficiency revealed by thyroid loss. That metabolic diversity produces different degrees of disability when no thyroid gland can compensate for it.

It results in a wide range of FT3:FT4 ratios in blood when diverse people are dosing the exact same ratio of thyroid hormones, in this case, a ratio of 1:0 micrograms of LT4 to LT3.

It is simply a way of dividing the population into three subgroups of disability by a scientifically-informed analysis of their FT3:FT4 ratios.

It was certainly not intended to become a target for laboratory results while dosing desiccated thyroid — or any thyroid therapy, for that matter.

Midgley’s research says nothing about what ratios in blood mean to health or symptoms during desiccated thyroid therapy.

Later studies by Midgley’s research team and other researchers do comment on symptoms in LT4 therapy, and they find that hypothyroid symptoms were more associated with a FT3 lower than mid- reference range, but were not associated with a particular FT3:FT4 ratio:

  • Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019). Functional and Symptomatic Individuality in the Response to Levothyroxine Treatment. Frontiers in Endocrinology, 10.
  • Larisch, R., Midgley, J. E. M., Dietrich, J. W., & Hoermann, R. (2018). Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer. Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association, 126(9), 546–552.

Basically, if a person is a poor converter, the first thing you could try is raising the LT4 dose, even to the point of lowering TSH, to see if it raises FT3 sufficiently to remove symptoms. If that does not work… well, try a T3-inclusive therapy rather than forcing the patient to suffer for the rest of their lives!

What is a normal FT3:FT4 ratio for patients on desiccated thyroid? Was hers too high?

I lament that there is no published research data I can refer to giving the range of FT3:FT4 ratios on desiccated thyroid (DTE/NDT). It’s a scientific problem and an ethical problem. Scientists have neglected the study of how this classic thyroid preparation works. Since the 1980s, many scientists have presumed that omitting T3 from therapy works well for everyone who no longer secretes T3 from a thyroid or converts T4 to T3 within thyroid tissue. Pharmaceutical prejudice against desiccated thyroid and biochemical bigotry have gotten in the way of logical, critical thinking and scientific and therapeutic progress.

In general, based on my informal observations of people’s lab results over the years, a person dosing desiccated thyroid is likely to have a ratio above the healthy control mean 0.32 in blood, and ratios such as 0.40 are possible but not predictable (an FT3 of 6.0 and a FT4 of 15.0, for example). It’s not necessarily harmful when a higher, fluctuating FT3 effectively compensates for a much lower quantity of FT4 becoming T3 in cells.

What was this patient’s ratio?

  • Her FT4 was 12 pmol/L (range 9-19)
  • FT3 was 5.6 pmol/L (range 2.6-5.8 ).
  • 5.6 divided by 12 is a ratio of 0.46.

Although her ratio seems unusually high for DTE, both of her lab results were in the normal range.

As for her symptoms, she said she used to feel great on this dose, but not anymore. Fatigue and brain fog, some insomnia, some increasing hair loss.

When feeling better, her FT4 was 16 and now fell to 12, and FT3 used to be 4.6 and now rose to 5.6.

Her former ratio was 0.28, and her current ratio is 0.46. Those are extremely different ratios. Yes, it could have been her ratio.

What caused her ratio to shift?

Her TSH was suppressed at both ratios, so we can expect very little T4 and T3 was newly synthesized in her thyroid.

The TSH is responding to the isolated higher FT3, but TSH is incapable of explaining to a doctor how well the lower FT4 is being metabolized by tissues beyond the hypothalamus and pituitary.

If a person has a TSH suppressed while FT4 is only 12 (9-19), and if FT3 is not tested (luckily hers was), a doctor could mistakenly suspect central hypothyroidism (pituitary or hypothalamic failure). Therefore, the FT3 result and her hormone dose’s T4:T3 dose ratio (4.2:1) are both essential information for monitoring her NDT/DTE therapy… as long as the FT3:FT4 ratio and TSH are not going to be misinterpreted as a health risk without appropriate evidence specific to this therapy!

As for the TSH, science now informs us that thyroid hormone ratio shifts will be perceived (processed) differently by different tissues. TSH, despite its acute sensitivity to thyroid hormones, is a local tissue response.

  • Enzyme expression: Many tissues in the human body convert T4 less efficiently than the pituitary and hypothalamus because they express different levels of D1, D2 and D3 enzymes as well as other enzymes that create T4 sulfates, T4, glucuronide and Tetrac.
  • T3 transport and metabolism: One must also consider how quickly T3 is transported into cells and metabolized to non-T3 by the very same set of transporters and enzymes that now concurrently carry and metabolize a significantly lower level of T4.
  • Receptor types: Most tissues beyond the hypothalamus and pituitary express beta-1 receptors or alpha-1 thyroid hormone receptors, not beta-2 receptors, and therefore, they may respond to dose-dependent T3 fluctuations less sensitively than TSH-regulating tissues.

Therefore, at this high hormone ratio anchored in a very low-normal FT4, TSH response cannot be an accurate judge of her global tissue thyroid status.

She could have become a poorer absorber of T4 hormone and/or a more efficient converter of circulating FT4 into T3. It is difficult to know how well she’s converting T4 because her FT3 is biased higher by the easy absorption of the 13.5 mcg of T3 provided by her 90 mg (1.5 grains) of desiccated thyroid. When FT4 is lower, T4 converts more readily to T3 via deiodinase type 2 (D2).

The peak post-dose is worth factoring in. It’s a key variable not seen in people with TSH-driven or TRAb-antibody-driven T3 secretion. She said she always takes her doses after her blood test in the morning, but she did not specify hours post-dose. If she tested 12+ hours post-dose, her FT3 fluctuates higher than this in the first 6-8 hours post-dose. This is not necessarily a problem for health. (See “Free T3 peaks and valleys in T3 and NDT therapy“)

When FT3 rises to a transient peak post-dose, it upregulates deiodinase type 1 (D1), which is richly expressed in thyroid, liver and kidney. T3 signaling may also upregulate deiodinase type 3 (D3) if tissues sense an excess influx of both Free T3 and Free T4 into cells. Both D1 and D3 enzymes have half-lives far longer than D2, and their activity may extend past the transient FT3 peak.

Alternatively, her thyroid gland fragment could be stimulated by TSH receptor-stimulating antibodies found in a small percentage of autoimmune thyroid patients. Or she may have developed a T3-secreting thyroid nodule. Or something in her diet may have altered her metabolic efficiency.

Some of the above causes are worthy of scientific pondering, and if ratio fluctuation persists, some may be worthy of further investigation with an ultrasound or antibody test.

But in practical terms, her ratio changed significantly on the same therapy. That is an a significant insight inaccessible without FT3 measurement and FT3:FT4 calculation.

She now needs a dose adjustment because she is symptomatic.

Are there health risks with low or high FT3:FT4 ratios on desiccated thyroid?

On desiccated thyroid, the FT3:FT4 ratios in blood are considerably higher than they are on LT4 monotherapy, and also range much higher than in healthy, undosed controls.

However, Hoang’s double-blind clinical trial of desiccated thyroid in 2013 did not remark upon FT3:FT4 ratios. It was also a very short term study.

Their conclusion was as follows:

Conclusion: DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T₄. DTE therapy may be relevant for some hypothyroid patients.”

(Hoang et al, 2013)

For more about this study, see “Review: Hoang’s 2013 study of LT4 and desiccated thyroid.”

To understand whether any patient on desiccated thyroid with high FT3:FT4 ratios is at risk of adverse health outcomes, we’d have to go to a study of longer-term dosing, such as this article:

  • Tariq, A., Wert, Y., Cheriyath, P., & Joshi, R. (2018). Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life. Southern Medical Journal, 111(6), 363–369.

They performed a study of long term DTE (NDT) therapy and synthetic LT4-LT3 combination therapy (mean 27 months, median 22 months).

  • There were no adverse effects on health, and patients reported greater improvement of quality of life with DTE therapy.
  • Unfortunately, they did not report FT3:FT4 ratios, and the dosages of DTE were very low on average, not likely a full replacement dose.
  • Their lab results were “normalized.” They were even more successful at keeping TSH, FT3 and FT4 all within reference range on DTE than on synthetic LT4–LT3 combination therapy.

Ideally, future studies should divide the population into tertiles by FT3:FT4 ratio to see whether the ratio alone is a significant variable for health and symptoms.

It makes a difference when a higher ratio is anchored in a lower FT4 or a higher FT4. A wide range of ratios and FT4 levels can be expected as thyroid disability combines with underlying peripheral metabolic disabilities. Dosing T3 in the presence of a lowered FT4 is very different from continually secreting T3 and converting T4 to T3. What is abnormal may be therapeutic to a disabled person.

But we already have far more information from NDT/DTE clinical practice than we do from published retrospective studies or controlled clinical studies.

LT4 synthetic pharmaceuticals became available in 1949.

If NDT was such a horrible, harmful medication, why did medical practice drag its feet for more than 20 years before shifting the prescribing trend toward synthetic LT4? NDT/DTE remained the gold standard therapy until the mid-1970s.

They didn’t have sensitive FT3 and FT4 tests back then, but part of the concern was the high Total T3 peak post-dose. Reports during the era did show that a minority of patients experienced hyperthyroid symptoms on desiccated thyroid, but the same could be said of patients overdosed on LT4 with continually high Total T4 levels and often high Total T3 levels as well. Regardless of the thyroid pharmaceutical, the solution was to adjust the dose.

In the 1970s, opinion shifted and prescribing practices changed — not based on published evidence of poor health outcomes, but based on concerns about biochemical abnormality and the fear of variation in potency due to the state of NDT pharmaceutical regulation at that time. There is no published evidence that high T3:T4 ratios were the cause of any health problems in the vast majority of patients.


Clearly, physicians need better training in thyroid science literacy.

This why we as patients need to be armed with good scientific literacy and an understanding of FT3:FT4 ratios in case we have a doctor who makes a mistake like this.

Let’s review the mistakes that led to this confusion and potential for harm.

#1. It was more confusing than helpful to speak of a bloodstream ratio in dose ratio 4:1 format.

Whether a study like Roef’s 2014 or Midgley’s 2015 article was the source, the 4:1 expression disassociated the ratio from its likely published source. It made it difficult to trace back to a research study.

No one has time, and few have the skill, to do this kind of detective work.

As a physician or patient, you have to know the evidence at the source of a numeric ratio before you know how to use it properly.

If the source is not dividing pmol/L by pmol/L, you can’t apply the ratio to someone whose results are in pmol/L. Picomoles are not picograms. The conversion factors differ for T3 and T4 and causes “ratio skew.”

If you can’t easily associate an incorrectly-expressed ratio with a study, you can’t even discover whether the study established a cause-effect relationship, proposed a therapy target, or who was included and excluded from the study.

#2. No one should make the mistake of thinking that a description is a prescription.

A finding in scientific research describes something about a population of interest.

Sometimes the description expresses a statistical boundary of risk, a turning point at which a health outcome becomes more likely.

But a risk association is not a therapy target.

Sometimes, as in Midgley’s article, it is simply a boundary between two or more categories of patients.

A descriptive category in thyroid therapy is also not a therapy target.

#3. No one should apply research findings from one population to a very different population.

A FT3:FT4 ratio of <0.25, when obtained from pmol/L data, is a proposed threshold for poor conversion while on LT4 therapy. It is certainly not what the ratio “should be” in blood on desiccated thyroid therapy.

Even if 0.32 or 0.30, the average FT3:FT4 ratio in untreated, healthy people was given as a therapy target, we’d have to ask this question:

Why should the statistical average ratio in a healthy population be conducive to health in every individual in that population?

Isn’t that like saying every woman should wear US shoe size 7, because that’s the statistical average for shoe size among women?

A range of healthy FT3:FT4 ratios exists both within and outside of thyroid therapy, although the range is far wider in thyroid disability and thyroid therapy.

This logic expresses the health risk and vulnerability of thyroid patients:

  • Nobody tries to “fix” healthy people’s FT3:FT4 ratios in blood to make them conform to their population’s statistical averages. They allow statistical outliers to remain where they are, as long as they are not diagnosed with hypothyroidism or hyperthyroidism.
  • Unfortunately, doctors can try to “fix” patients on thyroid therapy to force their FT3:FT4 ratios in blood to conform to a statistical average in a population to which they do not belong. This is because they are already subjected to a therapeutic intervention and their ratios may be monitored.

Therefore, thyroid patients on therapy are more vulnerable to the misuse of descriptive averages from other populations because their blood levels are subject to monitoring and manipulation.

What can patients do if we find ratios from research being misapplied to our therapy?

At very least, we can ask the physician,

“Can you refer to a scientific publication that I can read that explains how this is a therapy target that applies to me?”

If we are well informed, we may be able to explain that a FT3:FT4 ratio of less than 0.25 while on LT4 monotherapy places one in the category of “poor converter” of T4 to T3 hormone, according to Midgley et al, 2015.

If you are on desiccated thyroid therapy, you are not likely to be at risk from a handicap of poor conversion, but you may be at risk of ratio elevation if you are a very good converter of T4 to T3.

Implications for scientific research

The research so far gives no sign of any harm from high ratios when they are derived from thyroid therapy rather than TSH-stimulated healthy thyroids, and when a high ratio is not causing excess or deficient T3 signaling in the individual’s extrapituitary tissues.

Fortunately, the current research is revealing that even a normal TSH is blind to metabolically significant thyroid hormone ratios within the normal range, and that even “normal” TSH receptor stimulation is not always benign. We have to move beyond TSH-centric judgments of peripheral tissue thyroid status.

We simply need more research on long-term desiccated thyroid therapy by scientists who are not excessively fearful of T3 hormone … Hopefully we get more than just TSH-normalized short-term clinical trials that compare NDT with LT4, but also studies that recruit people happily dosed on NDT for many years or decades at various levels of TSH, FT3, and FT4.

Dear scientists, please find out what many of us as thyroid patients suspect is the case … that people with high FT3:FT4 ratios who achieve symptom relief while on thyroid meds do not necessarily develop type 2 diabetes and do not always struggle with obesity or heart diseases.

  • Tania S. Smith, PhD
    Thyroid patient and thyroid science analyst
    President and founder, Thyroid Patients Canada

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