In contrast with a long list of over 70 medical research articles on low T3 syndrome that excluded thyroid patients, I have only found three (3) studies so far that included patients being treated for hypothyroidism.
I’ll reveal their treasures and disappointments in reverse date order:
- Somppi, 2017
- Tevaarwerk, 2014
- Wadwekar, 2004
Here’s how many patients they studied:
- NINE (9) female patients with mold exposure, chronic fatigue
- TWO (2) people not critically ill, a woman and a man.
- SIX (6) men with various acute illnesses.
If you are reading this as a thyroid patient who has suffered low T3, your heart may first rise in hope! Next, as you read about the second one, you may pine in sympathy with your brothers and sisters. Finally, as I tell you about the third study, you may fall into a grumpy state. But we’ll call out together for change.
NOTE: To clarify, if you take away the word “syndrome” after Low T3, you will find additional studies showing a Low T3 level in T4-treated thyroid patients, but the patients with low T3 are usually < 30% of a larger population of patients, not the focus of the study. Whenever thyroid patients suffer a low T3, the phenomenon is not usually discussed in the context of “non-thyroidal illness” (NTIS). These studies used NTIS as a major framework and category. That’s what is so unusual about them.
STUDY #1. IF T4 THERAPY FAILS, T3 CAN HELP
Somppi, 2017 — “Non-Thyroidal Illness Syndrome in Patients Exposed to Indoor Air Dampness Microbiota Treated Successfully with Triiodothyronine”
This study is to a thyroid patient like a warming ray of sunshine and healing.
This retrospective case study of NINE female patients with indoor chronic mold exposure had been treated with T4 monotherapy “without success” with multiple symptoms and health disorders.
First, they tried to support the patients’ traditional T4 therapy with diet, nutritional counselling and adrenal support when necessary.
If this did not help them improve, T3-based therapy was initiated over a 2-week transition, and the nutrition and adrenal support continued.
The article provides tables describing their individually-adjusted dosages of T3 and T4, their TSH, FT4, and FT3 levels and the number of months it took to achieve satisfactory results (from 3 to 36 months).
Their overall health status and symptoms greatly improved with T3 monotherapy or T3+T4 combination therapy. This study provides detailed data on clinically-evaluated symptoms.
The discussion section covers the justification of the therapy, partly based on Reverse T3 (RT3) and T3 testing and literature about deiodinase activity. The author explains the rationale for a gluten-free diet and how it was implemented.
It is very unusual for any study of nonthyroidal illness, and not just because it includes treated thyroid patients.
- It studies the phenomenon in a chronic condition, not a critical, acute illness.
- It examines a category of chronic illness that has not been well studied in contemporary medicine (mold exposure).
- It takes a holistic perspective on the patients’ overall health and quality of life, rather than just a disease-specific approach. It focuses on not just biomarkers, but symptoms.
- It’s a successful intervention study. A lot of studies of T3 therapy in normo-thyroid NTIS populations avoid any intervention at all. When they do intervene, results have been inconclusive, or not so positive, but some have shown benefit.
- It’s a long term study showing the follow-up period after therapy.
On the positive side, it’s great to have a publication that proves therapy can succeed in Low T3 syndrome. It is a very helpful outline for a patient and beginner-clinician’s use.
On the negative side, the article can be viewed by anti-T3 clinicians as biased toward T3 therapies, almost as advertising for the clinic. Research and therapy was ethically supervised through a private functional medicine clinic in Finland. Upon reviewing the author’s clinic website, Amplia clinic in Tampere, one learns Somppi is vascular surgeon who has written popular-non-fiction books on therapeutic nutrition and who supports thyroid therapy through a “hormonal imbalance” program.
It might have appeared more objective if there was any data on a patient not recovering on this therapy. Yet they did honestly report it took one patient 36 months (3 years) to achieve an optimal state of health.
The article would be aided by more detailed scientific data on the therapies and biomarkers before and after the change in therapy. Somppi did give a useful table showing each and every patient’s pre-T3-therapy doses, TSH, FT4, FT3, RT3 and even their FT3/RT3 ratio. However, it needed information about how they changed over time when T4 doses were elevated or decreased.
A major weakness is that these patients, while on T4 monotherapy, did not seem to qualify for the label “Low T3 syndrome” because their Free T3 numbers ranged from 3.5 to 6.8 pmol/L. Most Free T3 levels were 4.2 or higher. Only the lowest value of 3.5 seems low enough to be below reference, but the laboratory ranges were not provided. Qualifying these 9 women to fit within the category on the basis of their FT3/RT3 ratios is a shaky foundation, especially since many studies of this syndrome use Total T3 to calculate ratios, not Free T3.
The discussion section’s reasoning regarding NTIS is very thin and relies on insufficient literature review, only Escobar-Morreale’s 1995 study of … rats. It would be expected for a study such as this to cite an article on NTIS in humans, a more recent one than 1995 (for example, Dietrich et al, 2015), to argue that these patients were similar enough to normo-thyroid patients with NTIS, in terms of their biochemistry.
Finally, it is unwise of Somppi to use Escobar-Morreale’s study to dismiss plasma levels of thyroid hormones as a useful global estimate of peripheral conversion efficiency across all tissues. Clinicians rarely need to assess tissue T3 sufficiency in any isolated tissue, such as only the kidney, or only the brain. The global net T3 and T4 supply to tissues that exchanges with tissues in both directions is a meaningful diagnostic target (Dietrich et al, 2016). If one goes too far down the road of dismissing bloodstream thyroid hormone concentrations just because they differ from an individual tissue’s local concentration, it supports the misguided policy of throwing FT4 and FT3 tests in the trash! Clinical interventions like these rely heavily on these indicators.
This article is freely available via open-acess in Frontiers in Immunology. doi: 10.3389/fimmu.2017.00919
To thank & encourage Taija Liisa Somppi: email firstname.lastname@example.org
STUDY #2: BEING A POOR CONVERTER OF T4 CAN DO THIS TO YOU
Tevaarwerk, 2014 — “Two patients with atypical low triiodothyronine syndrome: primary deiodinase abnormalities?”
This study is to a thyroid patient like a rainy day of suffering recorded.
Someone noticed us!
This study examines non-traditional causes of the biochemical syndrome seen in nonthyroidal illness, but without the usual severe illness, in TWO patients treated with T4 monotherapy.
A 63-year-old man had chronic heart failure and was very symptomatically hypothyroid but wasn’t critically ill. His Free T4 was at upper limit of reference but Free T3 was low and his RT3 was high. Increasing his dose of levothyroxine to 100 mcg didn’t help his symptoms, increased FT4, and slightly increased RT3 and lowered the TSH. But the increased dose gave no benefit to FT3 levels. It only boosted FT3 by 0.3 pmol/L temporarily. The FT3 fell back down on a repeat test.
In fact, to me, his discordantly high TSH and high T4 look like a case of a “partial SBP deficiency” like my own — his high T4 was unable to bring his TSH down into reference, while his T3 was stuck below range like it was imprisoned there. (Dumitrescu et al, 2010)
A 60-year-old woman also wasn’t critically ill, but was obese and very symptomatically hypothyroid. Her Free T3:T4 ratio was also high and her FT3 low, but RT3 was within normal. Increasing her dose to 150mcg T4 was equally useless: it didn’t help her symptoms. It raised FT4 and suppressed TSH without making much difference in FT3 – it actually lowered FT3 by 0.1 pmol/L.
The article focused on trying to understand what the biological “cause” was of their abnormal thyroid lab test results. The clinician tweaked their therapy, but giving them more T4 did not fix it.
The main puzzle for the author was that these people were not ill enough to require hospitalization, even though they were both suffering horribly with symptoms.
In science, even one negative example can disprove a theory and should spawn inquiry.
Theory disproven = that illness is the only cause of low T3 syndrome.
A nonthyroidal “illness” is not needed to “cause” low T3 in people with hypothyroidism who are on T4 monotherapy. All they need is an oversupply of T4 they can’t metabolize.
And you guessed it–adding T4 won’t help them.
Unlike Somppi’s study, it wasn’t a study of the relationship between their FT3 levels and their symptoms or health outcomes over the long term. It was just a short term comparative case study.
Unlike Somppi’s study, there was no successful intervention. Nobody reached for the T3 pill bottle. The researcher sat in a scientist’s chair and coolly pondered their biochemical anomaly, suggesting but not proving that they could have a DIO1 and/or DIO2 genetic polymorphism.
We don’t know what happened to these sad cases. Did they ever get help? Did they eventually end up in hospital? Are they still on T4 monotherapy?
Have they died yet?
Anyone want to ask? He may be Canadian. The article says “Gerald J. M. Tevaarwerk, University of Western Ontario. Email email@example.com ”
STUDY #3: WORRY NO MORE WITH TSH AND T4!
Wadwekar et al, 2004 — “Thyroid hormone indices during illness in six hypothyroid subjects rendered euthyroid with levothyroxine therapy”
This study is to a thyroid patient like the darkest night of false reassurance to doctors who will then keep sufferers in the dungeon.
This study is about 6 men — men “rendered euthyroid” by brand-name Synthroid — who had a few days of NTIS while being treated for acute conditions.
Like Tevaarwerk’s study, it’s interested in their “thyroid hormone indices.”
The researchers never use the term “low T3 syndrome.” They talk about all their biomarkers equally, which were Total T3, Total T4, Reverse T3, and TSH measured on day 1, 3, 5, 7 and pre and post-discharge.
- Total T3 only fell below range on Day 1-3 and was borderline low-normal by day 5.
- Total T4 was low on days 1-3. Then it rose back up steadily from days 5-7.
- TSH fell from 2.1 to 0.57 on average by day 1, a bit lower on day 3, and then started to rise by day 5, was above range on day 7, then back to normal on discharge.
You’ll notice the increased TSH secretion and its concurrent effects on T3 and T4 rise. Hm, that TSH was stimulating something, because their T4 dose was unchanged.
Was it likely these men were relying on some residual thyroid gland function, and their living thyroid tissue, even if minimal, could have been the key to their recovery?
However, the researchers greatly minimized the contribution of the gland in their report.
Instead, they reasoned that the men recovered based on their master-gland saviours, the hypothalamic TRH and pituitary TSH, directly influencing the disordered thyroid hormone metabolism “with minimal contribution by the altered synthesis and release by the thyroid gland.”
Indeed, you can’t prove how much their thyroid gland helped them recover if you don’t study 100% thyroidectomized people!
Since they don’t say whether or not these people had their thyroids removed, you can assume they had thyroids.
They do NOT represent the thyroidless among us. It’s an important factor because the healthy thyroid tissue plays a key role in recovery according to many NTIS researchers.
Another question is worth asking — Were these people good converters of their T4 medication?
If you look at their data tables, it shows the six men they studied were, on average, superconverters of T4 — virtual engines of T4-T3 productivity.
Their average T4 before and after was mid-range. Their average T3 before and after was not lagging behind by much, not far below mid range. Obviously they did not have chronic low T3 before their hospital stay.
These men were very efficient at metabolizing their T4 meds before and after, so it’s likely Levothyroxine was a good choice for their therapy. In any case, Synthroid was enough to get them through their acute short-term illness in hospital.
This study was unlike both Somppi’s and Tevaarwerk’s. The authors emphasize how “normal” and “appropriate” everything was during their illness.
Here’s Wadwekar’s conclusions with my emphasis in CAPITALS:
“Alterations ensuing during a SHORT stay in the hospital due to an acute illness in subjects with primary hypothyroidism rendered EUTHYROID with APPROPRIATE replacement therapy with Levothyroxine (LT4) are almost identical to those in NORMAL subjects. These changes are probably secondary to altered thyroid hormone metabolism. The altered levels of thyroid hormones and TSH noted in these subjects are TRANSIENT and THEREFORE providers should REFRAIN from initiating frequent changes in daily LT4 replacement dose during the acute illness in these subjects.”
Well, this is odd. Studies of normal people who undergo acute illness do not continually harp on how normal they are or how appropriate their therapy is.
Their main goal appeared to be to instill a sense of calmness and trust in the safety of 100-150 mcg / day of Synthroid during acute illness.
It might as well be a Synthroid ad.
Mother Nature and Synthroid are working hand in hand. Aww, how nice.
But we know Mother Nature is not always nice. People do die in NTIS.
The study cited a lot of low-T3 / nonthyroidal illness research studies “in normal subjects” to reassure the reader that these people were just like “normal” people. But they never mentioned how tragically “normal” were the death rates or morbidity rates examined in those other studies.
That’s a major blind spot that makes it more like a drug promo than an objective study — not acknowledging any risk to health whatsoever.
Were the researchers ever worried about their low T3 levels?
The completely avoid even mentioning T3 therapy, and indeed T3 was not the only hormone that went temporarily out of range on days 1 and 3.
T3 was dangerously low on day 3, at 43 ng/dl (90-190). Onward they went with their experiment, having faith in TSH and T4 to save their research participants who had consented to be studied.
The most urgent, pressing, critical research question the researchers addressed is whether or not to adjust their T4 dose. (I’m being sarcastic, of course.) Do these people not realize how pointless an intervention it could be to give them more T4 when it’s being destroyed by the body, according to earlier studies like Brent & Hershman’s in the 1980s? It’s as if that’s the only option that should ever be on the table for any thyroid patient who goes through nonthyroidal illness: merely to tinker with T4 dose or not to tinker.
The answer was definitive. Do not intervene with “hypothyroid subjects rendered euthyroid.”
“therefore providers should refrain from initiating or making frequent changes in daily LT4 replacement dose during the acute illness.”
But they didn’t have an arm of their study that tinkered and caused harm, so why exactly should we not tinker?
This is a dangerous leap to a conclusion you can’t draw for everyone based on 6 superconverters of T4 who likely had residual thyroid gland status.
When you do research on 6 male superconverters and conclude that doctors should refrain from intervention or concern for EVERYONE in this category of disabled, vulnerable people, you’re jumping to a conclusion that crushes research inquiry and dismisses therapeutic innovation.
To ask further questions, here’s contact info for one of the co-authors: Udaya M. Kabadi, M. D., VA Medical Center, Iowa City, IA. Udaya-Kabadi@uiowa.edu
In these three rare studies of thyroid patients with Low T3 Syndrome, we see a variety of approaches to nonthyroidal illness and define the syndrome differently.
A lot depends on the paradigm, goals, and stance of the researchers.
- One is a clinician-researcher motivated by patients’ suffering, and the intervention not only helped these patients but the publication itself could help future patients.
- A second appeared to observe us like lab rats, with some sympathy for the rats’ symptoms. Our lab numbers are interesting or puzzling anomalies but give them no motive to actually do anything to help patients.
- The third defended the normality of TSH-normalized T4 normo-therapy in a few strong men. They used the men’s survival to convince people that thyroid patients’ low T3 during acute illness is temporary and above all, normal.
Yay! we were included three times. Should we be eternally grateful? Should we stop whining about not being included in NTIS research?
Are you kidding?
Three small-scale studies, all of which had their failings, is NOT enough.
Worst of all, we are at risk of being the stuck in the state of patients in study #2 because of study #3’s naive call to inaction.
We are currently in a situation where doctors believe the false reassurances of study #3 and are thinking we are all safe in the arms of Synthroid when acute illness comes our way.
After all, they will say the suffering man and woman in Tevaarwerk’s study #2 were not acutely ill and didn’t die during the study. Plus, the man’s TSH was above range! (They won’t notice that T4 dosing wasn’t able to fix it.)
Naysayers could say that the people in Somppi’s study #1 didn’t qualify as low T3 syndrome patients and were healed of a pseudo-illness for the sake of profit.
Debate all you want amongst yourselves, researchers. We may live symptomatic lives with chronic biochemical NTIS, we may suffer worsened chronic diseases with NTIS, we may die as we go through a critical illness with NTIS.
This is still a case of our exclusion from the vast majority of non-thyroidal illness research.
Our quality of life, if not our life itself, is at risk from scientific prejudice and medical inaction.
Brent, G. A., & Hershman, J. M. (1986). Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. The Journal of Clinical Endocrinology and Metabolism, 63(1), 1–8. https://doi.org/10.1210/jcem-63-1-1
Dietrich, J. W., Müller, P., Schiedat, F., Schlömicher, M., Strauch, J., Chatzitomaris, A., … Lehmphul, I. (2015). Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling. European Thyroid Journal, 4(2), 129–137. https://doi.org/10.1159/000381543
Dietrich, J. W., Landgrafe-Mende, G., Wiora, E., Chatzitomaris, A., Klein, H. H., Midgley, J. E. M., & Hoermann, R. (2016). Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Frontiers in Endocrinology, 7. https://doi.org/10.3389/fendo.2016.00057
Dumitrescu, A. M., Di Cosmo, C., Liao, X.-H., Weiss, R. E., & Refetoff, S. (2010). The syndrome of inherited partial SBP2 deficiency in humans. Antioxidants & Redox Signaling, 12(7), 905–920. https://doi.org/10.1089/ars.2009.2892
Somppi, T. L. (2017). Non-Thyroidal Illness Syndrome in Patients Exposed to Indoor Air Dampness Microbiota Treated Successfully with Triiodothyronine. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00919
Tevaarwerk, G. J. M. (2014). Two patients with atypical low triiodothyronine syndrome: Primary deiodinase abnormalities? Endocrinology, Diabetes & Metabolism Case Reports, 2014, 130055.
Wadwekar, D., & Kabadi, U. M. (2004). Thyroid hormone indices during illness in six hypothyroid subjects rendered euthyroid with levothyroxine therapy. Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association, 112(7), 373–377. https://doi.org/10.1055/s-2004-821012
4 thoughts on “Low T3 syndrome in thyroid therapy: THREE studies”
My question for the researchers would be “what do you mean by rendered euthyroid”? Do you define it by “TSH anywhere within the reference range?” The true definition, of course, is “having a normally functioning thyroid gland.” How do you know when a patient’s thyroid gland is functioning normally? Are you aware of the fact that there are millions and millions of people with a TSH measurement somewhere within the reference range that are very, very sick? You are? And do you then tell these people, “Since your TSH is in range, your problem must be something other than your thyroid”? Do you then subject them to one test after another, many expensive, some painful, trying to prove your theory that something other than their thyroid gland is causing their problems? What do you do for them once all your tests tell you nothing, and your patient is getting more and more sick?