Stop spreading the unscientific myth about the normal T4:T3 ratio!

Sigh. Just sigh.

Even some of our best thyroid patient advocates can unknowingly share misinformation about thyroid therapy.

Mary Shomon’s thyroid articles on Verywell.com are usually to be trusted. But yesterday I was saddened to see that an article supposedly authored by Mary Shomon was spreading unscientific myths about “normal” thyroid secretion ratios being 13:1 to 16:1.

These statements are misleading. They are not truly representative of the wide range of ratios of thyroid hormone in health, according to science.

These 13:1 or 16:1 ratios have NEVER been clinically proven to be the only safe and effective ratios in thyroid therapy, but this is what people are being told.

To honor Shomon’s intelligence and insight, the best I could do was suspect that when her article was “Medically reviewed by Richard N. Fogoros, MD” it became coauthored by Richard, or its message got twisted by Richard.

Perhaps it was Richard Fogoros, not Shomon, who was naively believing the false theory that a long tradition of misguided T3-T4 combination therapy trials have been promoting without testing their own assumptions.

[NOTE October 21, 2019: Indeed, shortly after posting this message, my suspicions were confirmed by replies and messages from Shomon’s followers. VeryWell.com and their team may indeed be guilty of unethically hijacking her name and the trust that people have in her. I have now edited my citations of “Shomon” below to read “Shomon/Fogoros” to express doubts regarding its authorship.]

THE MISLEADING PASSAGES

Shomon/Fogoros’ article “Treating Thyroid Disease with Triiodothyronine (T3) Drugs” published September 26, 2009 said this:

“When combination therapy with both T4 and T3 are used, it can be difficult to maintain a normal T4-to-T3 ratio, which is between 13:1 and 16:1. In fact, several of the clinical trials comparing T4 alone to a T4 plus T3 combination ended up creating mild hyperthyroidism.”

Later down in the same article, this same statement is repeated:

“Proper dosing of Cytomel is relatively difficult. The normal ratio of T4 to T3 should be maintained, generally aiming at a 16:1 ratio. Furthermore, because Cytomel is relatively short-acting, its dosage should be split in half and taken twice a day. Combination therapy can be tricky, and should best be managed by an endocrinologist.”

Later, we get a similar statement in relation to NDT (desiccated thyroid)

Because NDT is much easier to prescribe than Cytomel (because there are no calculations involved aimed at preserving a normal T4-T3 ratio), it has become the drug of choice among many non-endocrinologists who treat thyroid disease.

However, NDT provides a ratio of T4-T3 that is not natural to humans (4:1 instead of 16:1), which tends to produce some degree of hyperthyroidism, and most experts still do not recommend its usage.

As you notice above, the second quotation uses this ratio to make a prescription about “proper dosing of Cytomel.”

It is telling us that dosing “should be maintained” at a supposedly “normal ratio of T4 to T3” which is supposedly 16:1.

Of course the article said a lot of nice and hopeful things about T3’s role in therapy. But at the same time, it propagated myths that can be harmful.

Yes, these myths can be harmful. They lead to unnecessarily restricting T3 doses in those who need more T3. Some people with thyroid disease simply don’t convert T4 hormone as efficiently as “normal” people, once their thyroid is dead or gone.

THE TRUE DIVERSITY OF RATIOS

I don’t wish to be demeaning to anyone’s intelligence when I state this fact.

This single 16:1 ratio is as false as the idea that the earth is flat.

There is no such thing in science as a static and universal T4:T3 ratio that is “normal” for everyone. There is a huge diversity of ratios in health. Therefore, ratios in thyroid therapy can also be diverse.

You will see it with your own eyes in the simple data displays I’ll show you below.

I can only hope that VeryWell staff or Shomon/Fogoros updates this article soon to edit these statements because they can do harm to people who genuinely need a T4:T3 ratio that is different from this.

(NOTE: I’ve backed up today’s version of the article on the Internet Archive in case it gets updated after my public correction and people think it never said this.)

THIS IS NOT A FREE T4:T3 RATIO.

Let’s keep in mind that Shomon/Fogoros’s article is targeting a lay public, not a medical reader.

To a naive reader, it might sound like they are talking about a Free T4 to Free T3 ratio, or perhaps a Total T4 to Total T3 ratio.

But no, that’s not what it’s talking about.

In healthy populations,

• Free T4:T3 ratios are around 3.17 to 1 (as calculated from Gullo et al, 2011).
• Total T4:T3 ratios are around 63 to 1 (as calculated from Andersen et al, 2002).

IT’S AN ESTIMATED THYROIDAL SECRETION RATIO.

Only people who read T3-T4 combination therapy trials (like the ones referenced in this Shomon/Fogoros article) would have even a faint inkling of where this 13:1 to 16:1 ratio comes from.

Those articles that Shomon/Fogoros references are recommending an LT4 to LT3 pharmaceutical dosing ratio.

They refer to the source as Pilo et al, 1990.

I know this study very well.

I’ve reviewed various aspects of this article before on thyroidpatients.ca.

• Question Pilo’s 1990 study. It can be misused to limit your T3 supply.
• Question Pilo’s study: The wide range of thyroid hormone adaptation
• Question Pilo’s Study: Thyroid Hormone Reductionism
• Question Pilo’s study: Iodine dosing biases T4:T3 secretion

This is not a study that made any recommendations for LT3 and LT4 dosing ratios for people with thyroid disease, and yet that’s what people are forcing this study to do for them. They incorrectly believe that thyroidal secretion should be translated into a static dosing ratio.

Pilo et al, 1990 is a study that estimated the wide variety of ratios of thyroidal secretion and peripheral conversion in 14 people.

Shomon/Fogoros’s article should have specified the “estimated average ratio of thyroidal secretion of T4 to T3.”

Because it’s an estimate.

Of an average found in 14 people in a 1990 study.

It’s an average of an estimated thyroidal secretion ratio.

NO SUCH THING AS A SINGLE RATIO

This overconfident wording makes it seem there there is only ONE ratio in all humans with healthy thyroids.

False, false, false.

The healthy thyroid gland is not a robotic mono-ratio-secreting organ. It is flexible.

Pilo’s calculated average secretion ratio was 1:16.83, BUT that’s an average.

Pilo and team found a wide range of T3:T4 ratios in healthy-thyroid humans, even among the 14 people studied who had a TSH between 1 and 2 mU/L.

SEE PILO’S DIVERSE RATIOS

In these numbers below, scan down the SRT4 (Secretion Rate T4) and SRT3 (Secretion Rate T3) columns.

Case 1, Case 2, Case 3 are each different people.

Notice how different the numbers are from each other.

Now let’s look at this same table after I’ve converted them all into ratios in the third column.

I have highlighted three numbers in yellow:

• the highest T3:T4 ratio (more T3 per T4, at ~1:6) is in human case 3.
• the close-to-average ratio is in human case 7, at ~1:14.
• the shockingly lowest T3:T4 ratio (less T3 per T4) is at ~1:71.

Therefore, Pilo also showed that some healthy thyroid glands secrete at a rate of 71 to 1 (T4 to T3).

Now look at Table 3’s data turned into a scatterplot:

Do you see any central tendency in this scatterplot?

Hardly any.

Do you see any cluster around case #7, closest to the statistical average of 1:16.83?

No.

The trendline isn’t even tracing a static ratio.

The trendline connects a ratio of 1:14.5 (Case 7) with a ratio of 1:24.89 (Case 13).

Instead, the trendline generally confirms the theory taught since the 1980s that when a thyroid secretes more T4, it secretes relatively less T3, and vice versa.

Next, if you imagine that Pilo’s highest T3:T4 ratio of “1 to 6.43” establishes a limit beyond which nobody should ever pass if they want to be healthy, think again.

There is no reason to believe that even Pilo’s range of ratios is representative of everyone with a healthy thyroid gland.

• There are too few subjects in this study to determine where the most common secretion ratios are in all healthy people who don’t need thyroid therapy.
• Pilo’s secretion estimates do not represent the full range of T3:T4 secretion ratios because they do not represent the entire TSH reference range of thyroidal stimulation, only people with a TSH between 1.0 and 1.2 at baseline.
• In addition, these are calculations biased by iodine overdose. After the baseline thyroid tests were done, every day during the entire course of the experiment, patients’ serum thyroid hormone measurements were intentionally skewed low by iodine overdoses. (See Question Pilo’s study: Iodine dosing biases T4:T3 secretion.)

WHO WAS CASE # 7?

Let’s learn about the ONLY person who secreted a ratio of 14:1, according to Pilo:

• 27-year-old male
• weighing 82 kg.
• TSH of 2.0, (the highest TSH level in this cohort)
• Estimated conversion rate of T4 into T3 = 25.8% (this is the estimated percent of T4 secreted from his gland that converted into T3)

WHO WERE CASES #3 and #14?

How about the person with the LEAST T4 (estimated) coming out of his thyroid?

• 31-year-old male
• weighing 83 kg.
• TSH of 1.0, (the lowest TSH level in this cohort)
• Secretion ratio of ~1.6

How about the person with the MOST T4 (estimated) coming out of her thyroid?

• 59-year-old female
• weighing 60 kg
• TSH of 1.5 (mid-range)
• Secretion ratio of ~1:71

SEX AND AGE

Now think about sex and age bias. This is a cohort of only 14 people.

There were only 5 women, or 35% of this tiny population.

The women were significantly older than the men in this study.

• MEN: 19, 20, 26, 27, 31, 36, 44, 54, 65. Average = 35.77
• WOMEN: 43, 44, 48, 53, 59. Average = 49.4

Will patient #7’s thyroid secretion ratio be generalizable to children?

How about 90-year-olds?

HEALTH STATUS

We are told these people were healthy.

All we know is that they were “Fourteen clinically and biochemically euthyroid volunteers, aged 19-65 yr, with no history of thyroid, hepatic, or renal disorders” and that they weren’t taking any drugs known at that time to affect thyroid hormones.

No ultrasound was performed. No tests of iodine levels prior to iodine overdosing.

Pilo’s team did not assess thyroid disease or pituitary health by the measures we use today. They didn’t test for thyroid antibodies.

NO LONGITUDINAL STUDY

The entire experiment was based on data from a single baseline measurement of TSH, T4 and T3 levels.

Over time, we know that these levels fluctuate even in a single healthy person.

HOW DID CONVERSION RATIOS COMPENSATE?

Let’s think about the woman with the highest T4 secretion and lowest T3 secretion estimate.

How well did she convert this secreted T4?

Has anyone taken a look in Pilo’s article to realize there are ranges of conversion as well as secretion?

The human body is designed to compensate.

Thyroidal secretion (as it fluctuates) and conversion rate (as it fluctuates) work together like two hands clapping.

What is the goal of all these fluctuating, compensating ratios?

They aim to maintain healthy Free T3 levels in bloodstream, which varies from person to person regardless of a statistical average in any healthy population.

Free T3 is the true target of health, not a secretion ratio, conversion ratio, or dosing ratio (See Abdalla & Bianco, 2014).

ONE RATIO DOES NOT REPRESENT HEALTH

Now you can see it is no exaggeration to say this.

Anyone who says 16:1 is “the normal ratio” and that thyroid therapy should maintain this ratio is saying we should all become like Case #7, a 27 year old man.

Even more illogical is the belief that this applies to every thyroid disease patient, no matter how much living thyroid gland tissue they have.

Thyroids are flexible, variable-ratio-secreting glands.

Healthy people have a T3 pharmacy in their neck. It can give them any amount of T3 their body demands. We have to beg and pay for our T3 supply.

The hormone T3 is not inherently more dangerous than the hormone T4, which converts to T3 at variable rates.

This model is pushing onto vunlerable patients another unphysiological ratio.

The standard monotherapy has a ratio of 100:0, which is extremely unnatural but is supposed to be the gold standard!

This idea is a way of promoting yet another narrow-minded “mono-ratio-therapy” as if its the only safe way to dose T3 thyroid hormone.

Two of the passages in Shomon/Fogoros’s article cautioned us that breaking this rule about this ratio tends to cause “hyperthyroidism” — a very misleading claim.

How was that judgment made? Any thyroid medication can be overdosed — or underdosed.

There is no way you can rationally blame “hyperthyroidism” on a thyroid hormone in a pill at any ratio whatsoever, ranging from 100% T3 therapy to 100% T4 therapy.

People can even be grossly underdosed on 100% T3 therapy, as I experienced recently when my own FT3 dropped to 4.4 pmol/L and my TSH shot up to 15.00, while my FT4 was 0.5 pmol/L. My ratio is certainly not normal. I was not hyperthyroid. I was hypothyroid. I increased my T3 dose. Now I’m fine. At a supposedly abnormal ratio that works for me.

Whenever this thyrotoxic effect happens in clinical trials, it is because they are doing a controlled experiment with rigid and unrealistic trial doses and ratios.

Experiments are not like real thyroid therapy.

No doctor in their right mind should force a patient to take a dose and a ratio of thyroid hormone that is not right for them.