Clinical trials of T3 (Liothyronine) have been barking up the wrong tree. The limitations of their research designs are now actively harming patients who need T3 medication.
Prices for T3 have been rising, medical prejudice against T3 is rising, worldwide T3 shortages are occurring, and patients who truly require T3 are being harmed by denying them access to T3.
The worst of this crisis is happening right now in the UK, where the price for T3 is so high that cost is the primary reason for barring access to it.
As Dr. Chatterjee says in a recent MedScape news article on this issue, (1)
“The difficulty is that scientific evidence on the benefits to patients’ well-being is inconclusive; it is possible that clinical trials to date have not been adequately designed to determine this.”
I’m sorry, but the word “benefit” is in entirely inappropriate here.
Determining a benefit for T3 in therapy is not the most urgent issue.
The issue, as you can see in the quotations from patients, is the HARM of T3 withdrawal from those who do need T3.
What’s wrong with the current approach
The body of research on T3 “combination therapy” has been hindered by the desire to perform “randomized” clinical trials — double-blind. With placebos and controls. This point was eloquently argued by an insightful team of thyroid researchers in The Journal of Thyroid Research, 2018. (2)
The issue of T3 medication’s role in thyroid therapy is not about a competition to find out whether Synthroid beats Cytomel + Synthroid in ALL hypothyroid patients. If that were the issue, go ahead and do your randomized double-blind trials … and just watch how the research design averages away the diverse patients’ results into homogenized gray meaninglessness.
It is not the “random” thyroid patient who truly benefits from and requires T3 hormone in therapy.
It is the patient for whom T4 monotherapy has FAILED to restore true clinical euthyroidism.
Therefore, research to resolve this health crisis should focus on understanding the patients who truly suffer hypothyroidism and/or horrible side effects on T4 monotherapy.
These are the ones whose T3 levels, without a functioning thyroid, may be chronically too low for their individual body’s needs, and/or whose bodies react adversely to various amounts of orally administered T4.
Adverse effects of T4 therapy have been acknowledged throughout history, but the common approach to manage them is to reduce T4 dose, which can cause thyroid hormone insufficiency. Studies rarely focus on patients whose side effects entirely disappear on T3 therapy.
In addition, if a thyroid patient truly requires T3, they usually don’t just require a tiny amount.
Current trials tend to limit the ratio of T3:T4 in therapy to no more than 1:10 or even less, due to myths about the static hormone content in a normal thyroid gland, rather than targeting Free T3 levels in serum.
Such teeny weeny T3 doses do not entail an honest trial of T3’s role in therapy. Come on! This is like sprinkling a little fairy dust on poop to see if it smells better.
The kind of T3 research we need
If scientists would honestly ask the most important questions about T3’s role in thyroid therapy, they must study the patients who truly need it, and need a lot of it.
Study those who take larger ratios of T3:T4 than even desiccated thyroid provides.
Examine how they thrive with NO clinical or biochemical symptoms of hyperthyroidism — other than a suppressed TSH.
Yes, I said it. Please study those whose dose of T3 suppresses their TSH long term.
Why? Because T3 at doses that are effective for these people often suppresses the TSH.
Whether or TSH suppression is a benign or harmful aspect of higher-dose T3 therapy is something you can _begin_ to examine in such studies. One cannot presume it is harmful given the entirely different thyroid hormone profile.
As for the fears and ethics of suppressing TSH in research, simply study patients whose TSH is ALREADY suppressed for medical reasons prior to the study and during the study, rather than asking for permission to suppress TSH for the sake of a medical research experiment.
And please, please–would you finally return to the study of patients who have been maintained for years on T3 monotherapy?
Studies of human T3 monotherapy have not been done since the 1960s or 70s, before advanced testing technologies. Yes there were studies. Here’s one on liothyronine therapy in female infertility from 1958, a study of 38 women. Go look them all up and read them to do your literature review, instead of assuming there were none before you.
Medicine has also done numerous studies of rodents on T3 monotherapy while it has ignored this living human patient population.
These are patients who not only survive, but thrive on extremely low levels of T4, some of them without a trace of T4 in their blood, because they have T3 medication to compensate for the T4 that would have otherwise converted into T3.
And for heaven’s sake, don’t just do subjective questionnaires about how the patients “feel.” That’s not the point. These are people who already choose T3 because they know they feel better on it. Focus on tangible medical measures please.
Examine their medical history. Examine how their body responds to therapy and slight variations in T3 dosage.
Because their TSH is usually suppressed, you must measure well known markers of T3 tissue stimulation such as heart rate, body temperature, total and LDL cholesterol, ankle reflex response time, and sex hormone binding globulin (SHBG). We know from patient histories that some patients who had elevated cholesterol on T4 monotherapy now have very low levels on T3 therapy.
It would be enlightening to also learn how their therapy affects iron, cortisol, blood sugar, insulin, and markers of heart health and bone health, neurological hormones, mood and cognitive health.
But get to it already! Hurry up and study these people!
This is about patients’ lives and health, and time is of the essence.
You must find out right now why you are actively harming people by withdrawing their T3 or refusing to give T3 … to those who appear to truly need it and thrive on it.
(1) Source of Chatterjee’s quotation: https://www.medscape.com/viewarticle/907659?src=soc_tw_190118_mscpedt_news_mdscp_thyroid&faf=1#vp_1
(2) Hoermann et al, “Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?” Journal of Thyroid Research, 2018. https://www.hindawi.com/journals/jtr/2018/3239197/