Thyroid pharmaceutical prejudice: How it works

By Tania S. Smith.  Updated May 8, 2019

“Thyroid pharmaceutical prejudice” is simply a bias against one thyroid hormone pharmaceutical type in favor of another.

Prejudice claims that a particular thyroid medication is intrinsically unsafe or ineffective, for all patients under almost all circumstances.  It’s a type of “sweeping generalization” fallacy.

The main aim of this prejudice is to keep the majority of thyroid doctors and patients loyal to one thyroid pharmaceutical formulation alone.

Why do this?

I could think of many reasons, but two obvious ones are efficiency and profit (or cost savings). It makes therapy simpler and more convenient for doctors, for medical systems, and the favored pharmaceutical companies if you put all thyroid patients on one assembly line that you can all benefit from.

I’ll give three examples of pharmaceutical prejudice, and then I’ll discuss their harms and how they work their dark magic.

ALBERTA GUIDELINES

For example, a 2014 Alberta thyroid guideline document by “Toward Optimized Practices,” still published on the TOP Alberta Doctors website, states this:

“Use L-Thyroxine for thyroid replacement. DO NOT use T3, T3/T4 combinations, or desiccated thyroid.”

No explanation or rationale is offered.

A PHARMACEUTICAL JOURNAL ARTICLE

Another example is an overview in a pharmaceutical science journal from India. (Karshan & Randhir, 2011) state this:

“Product types available for thyroid replacement therapy include synthetic and natural combinations of T3 (liothyronine) and T4 (levothyroxine), and desiccated natural thyroid, with levothyroxine alone considered the drug of choice for thyroid replacement therapy.”

Again, no explanation or rationale is provided.

Who is doing the verb “considered” in this sentence? Who considers it so? Whose drug choice is involved?

I would not be surprised if both the Canadian and the Indian documents are alluding to the opinions of the global thyroid therapy influencers, the American Thyroid Association.

2012 ATA / AACE GUIDELINES

An official document stands behind many countries’ local prejudices against all but one pharmaceutical: the American Thyroid Association and American Association of Clinical Endocrinologists for the treatment of hypothyroidism (Garber, 2012).

Some of its statements about thyroid hormone pharmaceuticals seem fair and objective, but many are not.

Overall, the guidelines bias the field toward T4 synthetic medication alone. They arrange the other options in a hierarchy of preference, with desiccated thyroid at the bottom.

Under the section “L-Thyroxine treatment of hypothyroidism,” they begin with this historical claim:

“Since the generation of biologically active T3 by the peripheral conversion of T4 to T3 was documented in 1970 (128), L-thyroxine monotherapy has become the mainstay of treating hypothyroidism, replacing desiccated thyroid and other forms of L-thyroxine and L-triiodothyronine combination therapy.”

Using the word “replacing” is neither accurate or fair. L-T4 has not entirely replaced the other two pharmaceuticals in practice, and they acknowledge this later.  However, it appears to be one of the aims of these guidelines to severely limit synthetic combination therapy, T3 monotherapy, and to put a stop to desiccated thyroid therapy, as you can see below.

The passage then mentions clinical trials of combination therapy, briefly raising the debate over the ratio of T3 to T4 (not taking a stance) and saying that the potency of T3 in comparison to T4 is 4:1 or more likely 3:1. It then concludes that “It is not known if those who responded positively to L-thyroxine and L-triiodothyronine combination therapy will have long-term benefit and whether genotyping patients with hypothyroidism who are clinically and biochemically euthyroid will ultimately reliably identify patients with hypothyroidism who are most likely to benefit from combination therapy.”

Such a statement makes it appear that there is doubt of the long-term benefit from combining T3 with their preferred medication. But why would it decrease in effectiveness over months or years if it contains hormones identical to those secreted by the human body and is 3x more potent than L-T4? Why would it gradually fail to work, even if the recent trials they cite were short term? The articles mentioning effective long-term combination therapy published prior to 1980 have been ignored. It also strongly implies that these patients who may benefit are rare genetic exceptions to the norm who may require special tests to qualify.

It then concludes that “Treatment of hypothyroidism is best accomplished using synthetic L-thyroxine sodium preparations.” Such a sweeping statement implies “…for virtually every thyroid patient (except the very rare ones whom we permit to access combination therapy on our own conditions).”

Mentioning desiccated thyroid again a few paragraphs later, they acknowledge it as a bioequivalent form of combination therapy, but caution that each brand name and animal source is distinct: “The content of thyroid hormone and the ratio of T4 to T3 may vary in desiccated thyroid preparations depending on the brand employed and whether it is of porcine or bovine origin.”

Yes, it is true that the ratio and micrograms of T3 and T4 in Armour thyroid may differ slightly from ERFA Canada’s Thyroid, and that bovine is far less potent than porcine. This is fair and reasonable to mention. Yet these differences can be just as easily managed by staying with one brand of desiccated thyroid, just as they elsewhere recommend not changing brands of levothyroxine. 

Later in the guideline are found further doubts: “Animal-derived desiccated thyroid (see L-thyroxine treatment of hypothyroidism) contains T4 and T3. Since T3 levels vary substantially throughout the day in those taking desiccated thyroid, T3 levels cannot be easily monitored. Being viewed by some as a natural source of thyroid hormone has made it attractive to some patients who may not even have biochemically confirmed hypothyroidism and wish to lose weight or increase their sense of well-being (274). There are substantially more data on the use of synthetic L-thyroxine in the management of well-documented hypothyroidism, goiter, and thyroid cancer than for desiccated thyroid hormone.”

This statement acknowledges that monitoring T3 is more challenging, but at least does not deny that T3 is not possible or not worth monitoring at all, something that they deny to levothyroxine users. (It is actually because of their fear of high T3 on this therapy.)

Emphasizing this pharmaceutical’s reputation as “natural” (it is commonly known as Natural Desiccated Thyroid) in the same sentence as its misuse makes it appear that patients desire this medication for illogical and non-medical reasons.

The misperception of desiccated thyroid as a weight loss supplement does not need to be mentioned in this context, since it is also true of the way T3 and T4 pharmaceuticals have been misused. It’s just a way of piling more dirt on this medication.

Recommendation 22.1 of the guideline states, once again, that “Patients with hypothyroidism should be treated with L-thyroxine monotherapy.”

Recommendation 22.2 “The evidence does not support using L-thyroxine and L-triiodothyronine combinations to treat hypothyroidism.” However, this recommendation “was downgraded to Grade B because of still unresolved issues raised by studies that report that some patients prefer and some patient subgroups may benefit from a combination of L-thyroxine and L-triiodothyronine.” (Note: it is acknowledging, even with tentative doubt, that patient subgroups “may benefit” as long as they still take L-T4)

Recommendation 22.3 states “L-thyroxine and L-triiodothyronine combinations should not be administered to pregnant women or those planning pregnancy.” Also, “Recommendation 22.3 was upgraded to B because of potential for harm.” Note: there is a “potential for harm” but apparently not proof of harm, or it would be upgraded to priority A.

Recommendation 22.4 then denies one thyroid pharmaceutical to any and all patients: “There is no evidence to support using desiccated thyroid hormone in preference to L-thyroxine monotherapy in the treatment of hypothyroidism and therefore desiccated thyroid hormone should not be used for the treatment of hypothyroidism.” Also, they add that this “was a unanimous expert opinion.” It is very clear where they stand. Below, I’ll mention how they fail to prove “no evidence” exists.

Under the category “Areas for future research,” the guidelines state “An important question is whether a recent study had sufficient data to warrant revisiting why some patients seem to feel better on L-thyroxine/L-triiodothyronine combinations and whether we can identify them and safely treat them (136) with this combination.”

It is a clear sign of bias that a single study has prompted the need for further research on synthetic T3-T4 combination, but “no evidence” of desiccated thyroid calls for no future research. No call for research on it makes it clear that they are disposed to ensure that it remains unresearched, and therefore forbidden because it is unresearched. After this was published, some research on desiccated thyroid therapy was finally published (Hoang et al, 2013; Tariq et al, 2018).

The guidelines also mention under the category “Areas for future research” that T3 monotherapy may potentially replace levothyroxine, because one randomized trial was conducted (Celi et al, 2011). However, they are compelled to officially un-endorse the entire replacement of their favorite pharmaceutical. “The small size and short duration of the study as well as thrice daily dosing presently precludes considering L-triiodothyronine monotherapy as an alternative to L-thyroxine monotherapy.” Again, this statement is blind to the history of safe and effective T3 monotherapy since 1952 described in historical medical publications.

You may have noticed the kindly patronizing attitude toward their patients. They acknowledge that patients may prefer therapies other than the one they prefer, but they use subjective words like “feel better” to dismiss patients’ preferences as merely subjective, and they express doubts that any patients are capable of handling dosing more than once a day, and ultimately they raise fear by including warnings about safety.

HOW THIS PREJUDICE FUNCTIONS

How does this prejudice actually convince people?

Let’s look more deeply into the sinister sleights of hand.

It promotes fear of an unfavored medication and uses power to command and dictate.

They fear what would happen if a patient had the right to choose the thyroid pharmaceutical that yields the best overall quality of life and health.

In fact, thyroid patients’ health may be more at risk from lack of choice.

They command the doctor to prescribe, and the patient to take, their favored medication.

Simply commanding, in capital letters, “do NOT use” cements an opinion into policy.

They often rely on circular reasoning and restatement to “prove” foundational assumptions.

Here’s a simple paraphrase: “TSH monotesting proves T4 monotherapy to be the only effective therapy because T4 medication is effective at normalizing TSH secretion.”

This just says that if you expect a test result and get it, you have fulfilled your expectations. It does not prove that you have achieved effective therapy. You have verified that TSH and T4 have an inverse relationship. Isn’t that nice.

LACK OF KNOWLEDGE AS EXCUSE

The worst problem is that the most severe prohibitions against desiccated thyroid come from a place of utter ignorance, a foundation of nothingness.

They claim that “no evidence” supports desiccated thyroid–despite clinical literature on this form of therapy published over a hundred years (from the 1890s. See our link to a bibliography.).

First of all, a lack of data can’t prove or disprove any claim. You are left with an argument that has a big hole in it. Lack of data is no grounds for judgment or action.

Not knowing something ought to inspire inquiry. Instead, they use lack of knowledge as an excuse to stop more than a century of safe and effective effective use that continues today.

Declaring that guideline writers are in “unanimous” agreement attempts to use collective authority to compensate for lack of data. It can’t compensate.

Secondly, saying there’s a lack of clinical trial research proves the ignorance and bias of their own community of researchers over the decades.

Who is directly (ir)responsible for this lack of research within their own field of thyroid therapy? 

Thirdly, it is very difficult to prove that past research was not published without showing how diligently you searched for it with an honest hope of finding it. They point the finger back at their own faint efforts and exclusionary criteria for literature review. 

Just how did they search, and what were they looking for and why?

They say:

“A PubMed computer search of the literature in January 2012 yielded 35 prospective randomized clinical trials (PRCTs) involving synthetic L-thyroxine published in 2007-2011, compared with no PRCTs involving desiccated thyroid extract for all years in the database. Thus, there are no controlled trials supporting the preferred use of desiccated thyroid hormone over synthetic L-thyroxine in the treatment of hypothyroidism or any other thyroid disease.”

What keywords did they try?

Did their database go back before 1980?

Why are they only looking for “prospective randomized clinical trials (PRCTs)”?

Their committee’s methods have been set up with strict guidelines on what they have to include and exclude from their search. They follow trends in medical guideline-writing by admitting only what is considered a “gold standard” clinical trial by today’s standards.

But by following these trends, their criteria excludes a large number of medical reports published before 1980 that were not required to adhere to today’s standards.

The development of “PCRT” research design has a historical trajectory. Older medical research in endocrinology journals used a variety of methodologies and different language to categorize them. 

Why would any reasonable person doubt that research on desiccated thyroid was published according to the highest research standards of its own time?

There was an era when smart scientists were less biased against this pharmaceutical and actually studied it. Of course this literature exists (See our link to a bibliography.)

In this medical literature, there is a lot more evidence of benefit for all thyroid therapies than there is evidence of their harm.

But we’re supposed to believe that “good enough” evidence simply does not exist.

Fourthly and finally, They boast of the clinical trials of levothyroxine that their pharmaceutical prejudice has promoted. A number of these studies are likely funded by levothyroxine sales. 

Given the pharmaceutical empire their prejudice has helped to build, why wouldn’t there be 35 clinical trials for L-thyroxine in a four year period?

Why would you expect even one clinical trial of desiccated thyroid therapy given that LT4 has taken over the market? Desiccated thyroid is not a new medication.

PREJUDICE DISTRACTS

Pharmaceutical prejudice is also a distraction.

It’s like a magic trick. While you focus on the handkerchief, the magician palms a card.

What does it distract us from seeing?  The true aim of thyroid therapy.

Its true aim should be to optimize each patient’s thyroid hormones to remove the symptoms and health effects of both hypothyroidism and hyperthyroidism.

A variety of pharmaceutical tools can provide many ways discovering which therapy is best for the individual patient.

It should not matter if the patient uses desiccated thyroid, synthetic T3, or synthetic T4, — all or one of these can be combined or used individually to meet their needs.

Nobody, not even the latest edition of hypothyroid therapy guidelines, can predict in advance which thyroid hormone pharmaceutical, or which combination of them, will fully meet the needs of the patient and bring about the best thyroid health and overall health outcomes possible.

CONCLUSION

Thyroid therapy guideline-writing has resorted to claiming that inconvenient evidence simply does not exist.

Because desiccated thyroid has been neglected as a field of study for decades, we must all stop seeking evidence about this medication’s historical and present use.

In the absence of studies that meet their narrow criteria, their collective authority alone should be enough to convince us to stop using the very thyroid hormone pharmaceutical that happens to be their historical and ongoing competitor.

This is evidence-selective medicine, evidence-BIASed medicine.

This is a way of narrowing the pharmaceutical marketplace.

This is a way of focusing future research on their own priorities alone.

This permits only a small shift: the possibility of enhancing their pet med with tiny doses of expensive T3 for the rare patient who suffers.

Guideline writers should not be biased against history, should not limit therapy options, should not directly imbalance the pharmaceutical marketplace, and should not direct future clinical inquiry away from medications that compete with their favorite.

Guidelines like these will continue to be powerful vehicles for the transmission and maintenance of pharmaceutical prejudice in Canada and around the world … until we open our eyes to their bullying attitude and selfish aims.

REFERENCES

Karshan, P., & Randhir, S. (2011). Clinical perspective of hypothyroidism. Journal of Applied Pharmaceutical Science, 01(05), 64–68. Retrieved from https://zdoc.site/clinical-perspective-of-hypothyroidism.html

Toward Optimized Practice (TOP) Endocrine Working Group. (2014, April). Investigation and management of primary thyroid dysfunction clinical practice guideline. Retrieved from http://www.topalbertadoctors.org/download/350/thyroid_guideline.pdf

Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I. L., Mechanick, J. I., … Woeber, K. A. (2012). Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine Practice, 18(6), 988–1028. https://doi.org/10.4158/EP12280.GL

Hoang, T. D., Olsen, C. H., Mai, V. Q., Clyde, P. W., & Shakir, M. K. M. (2013). Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study. The Journal of Clinical Endocrinology & Metabolism, 98(5), 1982–1990. https://doi.org/10.1210/jc.2012-4107

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. https://doi.org/10.14423/SMJ.0000000000000823