2014 ATA therapy guidelines: 5. Research

This post continues my series of paraphrases of Jonklaas et al’s 2014 guidelines that I left unfinished weeks ago.

Posts in this series:

• 2014 ATA Thyroid therapy guidelines: 1. Levothyroxine
• 2014 ATA Thyroid therapy guidelines: 2. Ethics
• 2014 ATA Therapy guidelines: 3. Desiccated thyroid
• 2014 ATA Therapy guidelines: 4. Using Synthetic T3
• 2014 ATA therapy guidelines: 5. Research [this post]
• 6. [ not yet published; still in draft form]
• 7. [ not yet published; still in draft form]

Here I provide paraphrases and quotations of what they set forth for the “ethics” of research in thyroid therapy in Section 18, and what they recommend as topics for future research in thyroid therapy. I provide my comments throughout.

Q18. What ethics do you recommend in further research on thyroid therapy?

ATA: “On many questions in thyroid therapy, we haven’t been able to come to solid or strong conclusions because of a lack of data from randomized controlled trials.”

ATA: Currently these open questions about T3-T4 combination therapy are leading to an erosion of “patient care, patient trust, and informed consent,” and so we have an ethical obligation to pursue further research until we can “set a consistent standard of care” that removes doubts in patients’ minds about our good will toward patients.

COMMENT > In other words, they notice that patients are increasingly doubting endocrinologists. They think that more research will prove to patients that the guidelines are based on evidence.

As you can see in this statement, it appears they want to make sure that research will justify and build on their existing beliefs and priorities. They denigrate and deny critical and paradigm-shifting research by people within and outside of their elite club.

ATA: We must only allow certain types of research trials to “disturb” our “clinical equipoise” — which means “resolving clinical disagreement.”

COMMENT > The image we get here is of an entire field standing there in “clinical equipoise” — like a ballerina standing on her toe forever — and refusing to move forward due to internal disagreements. The word “equipoise” seems so “poised,” when really there is nothing graceful about the heavy-handed and exclusionary approach they take.

ATA: When doing valid research, you have to conduct it as a valid thyroid expert, not someone who has just claimed to publish books or internet websites.

COMMENT > Oh, so you have to have credentials to prove that you have been fully indoctrinated. Anyone might take a fresh perspective on a field in a mess, but only those who have an official designation of an endocrinologist specializing in thyroid will have their publications validated as research.

ATA: As a researcher, you can never criticize TSH testing, and you can’t advocate for “antiquated diagnostic tools such as basal body temperature readings or other therapies” at this time in history. This was only ethical at a point in history when TSH was not yet the standard of care.

ATA: You can’t test or promote “antiquated ideas” about therapy and judge them as current or still relevant. This would be equivalent to putting a patient with Type 1 Diabetes on a special diet promoted in the early 20th century instead of taking insulin.

COMMENT > This jibe about special diets is telling, as of 2019 when Type 2, not Type 1 Diabetes is having its clinical equipoise shift.  Clearly TSH is their idol. They are very defensive. “Don’t you dare disturb our clinical equipoise at the expense of our idol!” is what I hear. Perhaps they could see their way forward if they permitted people to question the TSH as the first and final voice on all diagnostic decision making in thyroid therapy. But if you want to be part of their special research club, you must bow down and prostrate your brain to this idol.

Dear ATA: Get over the TSH! It’s just one hormone that responds to thyroid hormones!  Your own science acknowledges that each gland’s response to thyroid hormone is unique and metabolizes T4 at a different rate. TSH is secreted by one gland, not the entire body!  Our syndromes and symptoms and health outcomes for thyroid hormones are body-wide, not localized to the pituitary.

ATA: You have to recruit a huge and broad sample that represents all patients across all health care systems and countries.

COMMENT > Really?  You said earlier that it would be a good idea to research targeted populations who might benefit from T3 combination therapy due to their low-normal or low T3 levels, and now you want a generalized mob to be your sample so that it reveals … generalized mud for results?

ATA: You have to make sure that the ratio of T3:T4 and dosage in a clinical trial is based on good preliminary studies that justify your dose. It has to be a dose and formulation that would not be contested by those who promote that type of therapy.

COMMENT > You see, they want only one model & hypothesis to be tested over and over and over again, a ratio of T3 to T4 in medication that is kept to a miniscule 1:13 to 1:20 (see ETA guidelines). This is mainly because the ingestion ratio must NEVER come close to that of their old nemesis, desiccated thyroid, which is at 1:4.2. They basically want studies to continue to show NO superiority (and no inferiority) for therapies that integrate T3 hormone.

ATA: Studies of T3:T4 therapy would have to be extended over time until enough evidence is gathered to resolve the dispute, and we would also have to replicate the results in other studies.

COMMENT > Wow, see how comfortable they are standing with such ballerina-like clinical equipoise. I hear them saying “Settle into your T4 monotherapy, dear patients.” It would take gargantuan efforts and decades of long-term studies replicated over and over for the ATA to admit to itself that there is any value to integrating tiny doses of T3 alongside the pharmaceutical preparation they champion. Many of today’s suffering patients will be long gone by then, perhaps due to a shortened lifespan from our low T3:T4 ratio in bloodstream that is starving organs beyond our pituitary glands. But at least our TSH secretion rate was normalized until the day we died!  Sheesh.

ATA: If you as a doctor want to conduct a case study with an individual patient to individualize their care, go ahead and do it with their consent and do it properly as an “N-of-1” study (research on a patient population of 1) to examine your innovative therapy. But realize that merely engaging in individual therapy is not really “research,” and no reports of individualized innovative therapy, even the best research of that type, can ever “resolve clinical equipoise” on a matter of debate.

COMMENT > In other words, they limit the word “research” to mean only big studies that are funded with millions of dollars of some rich industry partner’s expense.  Research, if you look it up in a dictionary, is a lot broader than that. Basically you’re telling doctors that they can deeply inquire into each patient’s therapy but they can’t call it “research.” This restrictive view ensures that money and large-scale statistics, not clinical concern and deep intellectual inquiry, rule thyroid research forevermore.

Those are their research rules!

COMMENT: TSH and the sacred T3:T4 ratio rule over ATA-led thyroid therapy research. In this system, only huge, long-term and well-funded research studies by card-carrying believers have the authority to persuade these self-proclaimed leaders.

Dear ATA and non-ATA researchers: You do NOT have to be ruled by these restrictive rules — unless you believe that becoming part of their exclusive club will advance your careers. The ATA has overstepped themselves by undermining researchers’ intellectual freedom. A truly ethical researcher should have the right to test any hypothesis they so choose, and to use any method they feel is appropriate to test it.  Let’s think outside this tiny coffin of a box.

And there’s more: At the very end of their document, here is what they recommend for future research topics, which show where they put their priorities:

ATA: Future directions

ATA: There are many unresolved questions in thyroid therapy, but we want “to improve the lives of our patients with hypothyroidism.”

COMMENT > No, ATA, you don’t. If you did, you’d open your minds as researchers and encourage research that helps you see the blind spots of your own paradigm!

ATA: More research is needed, but it should be of high quality, and it should meet our rigorous criteria.

ATA: General research:

ATA: Preventing overdose; standardizing compounded doses, considering biomarkers beyond TSH, long term study of desiccated thyroid to understand the consequences of its excess T3 concentrations, development of thyroid hormone analogs with more benefit than risk, and research on thyroid stem cells.

COMMENT > What an openly declared bias. In your opinion, there’s only one way to study desiccated thyroid, and it is to start by assuming it is a problem, not a solution. In addition, there is nothing here about UNDERDOSE leading to continued signs of hypothyroidism, which is too often caused by religious observance of the lower boundary of the TSH reference range in people on thyroid therapy.  The main reason you want to study “thyroid hormone analogs” is because of your distaste for T3 and your fear of T3 as a therapeutic hormone. How about studying why so many people outside of narrow research studies actually thrive on T3 therapies?

ATA: Areas for T4 research include:

Promoting patients’ compliance with therapy, improving therapy in pregnancy, understanding gel capsules, better FT4 assays.

COMMENT > Why is “compliance” #1 on their list? Maybe because you are torturing some patients and they are squirming?

ATA: Areas for T3 research include:

Understanding T3 levels in age and disease, understanding T3 levels in tissues versus serum, developing better FT3 and T3 assays, developing sustained release T3 and its use in trials of combination therapy at a ratio of 14:1 T4 to T3, understanding which “selected” patients could ever benefit from T3 supplementation if their T3 is low.

COMMENT > Finally something patients can wholeheartedly agree with. Study T3 in relation to age, disease, tissues vs. serum, and improve your T3 assays please. I’m going to stop there because it’s at this point you bow down to your idols again.

> Why should the sacred ratio of ingestion come in to usurp the ratio in blood and tissues?  The main reason you thirst for “slow release T3” is to find a formulation that won’t upset the TSH by means of fluctuations in Free T3 levels. It’s a pharmaceutical project that promises to line pockets with money long before it may or may not benefit patients. We already have slow release formulations in the US and they are problematic, and Bianco, co-author of this report has openly admitted this and has pursued the development of an alternative slow release formulation.

> Why not just work on a slow injection device, or a T3 patch? That would be nice for those of us who live without Free T4 in blood and currently take 5 doses a day to even out our FT3 levels.

ATA: “Finally, qualitative research may be informative in exploring the nature of patient preferences for particular [Thyroid Hormone] preparations. There is an absence of qualitative research in the area of evaluating therapies for hypothyroidism, which raises questions about the validity of many of the quantitative instruments used in assessing patient well-being on various formulations and dosages. Qualitative data are traditionally used to form the basis for more precise quantitative instruments; they also help to inform about covert socio-ethical barriers to well-being, which may affect how data are collected and/or analyzed.”

COMMENT > Tread softly on our preferences, ATA. You don’t live in these bodies that you treat. Each patient responds differently _biologically_ long before they have a social or emotional response to therapy.

When it comes to patient symptoms, ATA endocrinologists tend to look to psychology for qualitative methods. This could lead down the path to the nut-house for patients and their doctors. A group of mad scientists seems to be working very hard to maintain their own self-delusion that so many patients are deluded about their hypothyroid symptoms. 

We already have a system that offers a prescription of antidepressants for people who “imagine” symptoms while their TSH is normalized. It can’t be their thyroid, the reasoning goes, so it must be a broken brain.  An earlier section of their article referred to Munchausen syndrome, a false belief that one is unwell, which can make a person actually feel unwell.

This document already tried to remove a barrier when they responded to the patient belief that desiccated thyroid is more “natural” because it is animal-derived not synthetic and is better because it includes T2 and T1 and calcitonin.

Should one expect future ATA efforts to point out that additional “covert socio-ethical barriers” enable a subgroup of patients to believe that T4 monotherapy is making them well, and prevent them from realizing there are alternatives to T4 monotherapy that might serve them better?

[To be continued; See index of series at top]

Related posts about guidelines, and the ATA

• 2019 ATA article engages in patient-blaming and doctor-shaming
• Thyroid patient blaming and shaming, part 2: True barriers
• Thyroid patient blaming and shaming, part 3: Advocacy and Science
• How thyroid guidelines are being used to punish doctors
• 2012 ATA thyroid guidelines ask for clinicians’ independent judgment

REFERENCES

Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., … Sawka, A. M. (2014). Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid, 24(12), 1670–1751. https://doi.org/10.1089/thy.2014.0028