Sadly, a large body of so-called “peer-reviewed double-blind data” has failed us as Hypothyroid or Hashimoto’s patients.

On the negative side, there is research with biased results based on how poorly data was collected, results showing how poorly data was analyzed or interpreted, or research that seems to clearly support the $$money$$ of those who headed the studies.

On the positive side and below, there are a growing amount of studies/data/articles which completely match what informed thyroid patients had ALREADY figured out on their own, by their consistent and solid experiences and observations, for YEARS now!

Please note: if you use any of the compiled medical research information below, thank you for having the INTEGRITY AND HONESTY to state where you got it…here:

Thank you!

**FOUND MORE RESEARCH ARTICLES THAT WOULD HELP THIS PAGE?? Use the Contact below to send the link to the article or comment. Remember: I’m only seeking research that can be used to help doctors understand better thyroid treatment and that which is related, as well as which challenges their bad information.



  1. This eye-opening 1995 study firmly reveals that T4-only treatment does not ensure that all tissues are free from hypothyroidism aka euthroidism, and is thus not a recommended treatment! (And it is followed up by showing that only having T3 in one’s treatment does the job:
  2. From 2011 and the Journal of Clinical Endocrinology and Metabolism, this study showed that in rodents, just using T4 alone does not restore a euthyroid state in all tissues (which patients have found repeatedly and for decades). Its title is “Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine.
  3. Conclusions from this study show that more than 20% of patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. It concludes that a more physiological treatment than levothyroxine monotherapy may be required. Study is titled “Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients”. (See #5 below which shows 70%) Comment from Janie: And from reported patient experience, even with what appear to be adequate levels of T3, patients on T4 state they do NOT get the good results they do on desiccated thyroid.
  4. Thyroxine was no more effective than a placebo in improving cognitive function and psychological well-being in patients with symptoms of hypothyroidism. Thyroxine did NOT improve cognitive function and well-being in healthy participants.
  5. Despite a two-fold increase in total serum T3, free T3 in the cerebrospinal fluid (CSF) remained unchanged when one is on T4-only, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF.
  6. At the 90th annual meeting of the Endocrine Society, June 2008, it was announced that T3 can be an effective substitute for T4. And�the target TSH was .5 — 1.5, though we know it goes lower without issue. Comment from Janie: Even though being on desiccated thyroid, with its T4, T3, T2, T1 and calcitonin, is even better according to the experience of many patients, this announcement is at least a good step in the right direction. Hopefully, they will take the final step!
  7. Swedish Doctor at Karolinska Hospital in Stockholm states: Levaxin is the medicine that is offered to patients with Hypothyroidism. Approximately seven out of ten patients are not symptom-free. Stefan Sjoberg, endocrinologist and associate professor at the Karolinska Institute has therefore, together with his research team, shows that patients blood tests may show normal levels of thyroid hormones with T4-only due to not enough conversion to T3. Research underway at Halmstad Hospital.
  8. This study with patients who have no thyroid due to removal after cancer revealed that T4-only didn’t cut it:
  9. Here is 2015 research which catches up with our experiences. Namely, this research underscores that 1) T4-only treatment leaves residual symptoms 2) the TSH doesn’t reflect whether all tissues are getting enough thyroid hormones, aka, it states “While the molecular basis for the residual hypothyroid symptoms is lacking, it is generally hypothesized that these patients suffer from tissue-specific states of hypothyroidism and that serum TSH might not adequately reflect thyroid status at the level of different tissues. A T4/T3 combination, and even better NDT, is the way to go.
  10. Again, showing that T4-only (levothyroxine) and a so-called normal TSH, can result in continued problems. And since this came from an Endocrinology journal, I guess they would choke to dare mention that NDT would have been a great alternative:
  11. What’s interesting about this research is that pushing your T4-only too high (as a false way to treat continuing symptoms) can result in artery stiffness:
  12. Turns out that levothyroxine (which would also apply to any T4-only med) plays “a major role” in the risk of coronary heart disease and ischemic stroke in patients with thyroid cancer who received a thyroidectomy. At first the research implied high doses of T4, but also included low doses.
  13. Here’s a 1999 study which showed a connection between liver stress and levothyroxine (and which went away with the use of T3):
  14. From 2017 and the New England Journal or Medicine, this study found that levothyroxine was an inadequate treatment for those 65 years or older: Of course, the article mentioned the target for the TSH as 0.40 to 4.60 mU/L, since Endocrinology adores the crappy TSH test. And the participants may have been underdosed. But our worldwide experiences know that T4-only fails too many people.


From the Journal of Clinical Endocrinology & Metabolism, August 2018, they are FINALLY getting what we as patients have known for years—that T4-only leaves cholesterol too high. The research more fully questions whether T4-only is a wise choice at all. and this one:

HEART ISSUES (from T4-only or from a low FT3)

  • The Journal of Clinical Endocrinology & Metabolism has reported that long-term levothyroxine replacement therapy in young adults is associated with cardiovascular abnormalities. 2008 COMMENT: Of course, thyroid patients have known this a longggg time as they watched their cholesterol and Triglycerides rise while on a lousy T4-medication, and some end up with heart problems. But this finally gives some research on a FACT.

ADDING T3 to T4 (or even T3 alone, or NDT) GIVES BETTER RESULTS:

  1. Here’s a study from 1996 which underscored that both T4 and T3 are needed to remove hypothyroidism: (And it followed research from the previous year showing that T4-only did NOT do the job—see
  2. As far back as 1999, the New Journal of Medicine reported superior results of a synthetic T4 and T3 combination treatment, especially on the brain and other tissues.
  3. And another one titled Thyroid Insufficiency: Is Thyroxine the Only Valuable Drug, Journal of Nutritional & Environmental Medicine (2001), 11, 159�166
  4. And here’s another one from 2009 sent by Paul: (has a fee) but here’s where you can at least see the abstract: They evaluated depression and anxiety rating scales as well as patients own preference.
  5. Also this one:
  6. At first blush, this Amsterdam study appears to give the same propaganda of T4 only. But as you read on, it mentions this: Third, recent animal experiments indicate that only the combination of T4 and T3 replacement, and not T4 alone, ensures euthyroidism in all tissues of thyroidectomized rats. From 2001, Developmental Endocrinology to Clinical Research:
  7. John C. Lowe’s Four 2003 Studies of Thyroid Hormone Replacement Therapies: Logical Analysis and Ethical Implications Excellent article (16 pages) about the efficacy of using T4 and T3 in treatment, and not using the TSH, and so much more.
  8. Though weak in its conclusions, we have a study from 2016 titled “The History and Future of Treatment of Hypothyroidism” which, at least opens the door that combined therapy with T3 and T4 might be more beneficial. (And it sadly states that only 10-15% of T4 users “are dissatisfied as a result of residual symptoms of hypothyroidism”–we know it’s much higher than that who are not doing well on T4-only)
  9. From 2009 and the European Journal of Endocrinology came this research which concluded that T3 added to T4 is preferred over T4-only (in spite of the fact that the amount of T3 was probably too little for many of those they tested…yet they still preferred it.) They used depression and anxiety rating scales as well as patients own preference, with nearly half preferring the added T3 and only 15% preferring T4-only.
  10. At the 90th annual meeting of the Endocrine Society, June 2008, it was announced that T3 can be an effective substitute for T4. And�the target TSH was .5 — 1.5. Comment from Janie: Even though being on desiccated thyroid, with its T4, T3, T2, T1 and calcitonin, or T3/T3, is even better according to the experience of many patients, this announcement is at least a good step in the right direction. Hopefully, they will take the final step!
  11. This article concludes: Although the evidence base is not strong, there is a small group of patients who may benefit from combination T3 and T4 treatment due to difficulty tolerating thyroxine. Until further evidence is available, a case-by-case approach is recommended. From September 2017, and very limited—implying that it’s about a small body and the evidence is not strong, which hypothyroid patients know if completely false-
  12. VERY GOOD RESEARCH! How long term treatment with T4 and T3 does NOT cause “adverse effects and cardiac mortality” nor “additional risks of atrial fibrillation, cardiovascular disease, or mortality in patients of all ages with hypothyroidism.” This research FINALLY catches up to what we’ve known by our experiences for years now. Kinda makes you want to say “duhhh”, but glad to see the confirmation for doctors who ignore your clear improvements. 🙂
  13. Another study, 2020, that says some patients need T3, not just T4 (though it stupidly says we should be started on T4. Nope. We need T3 from the beginning.)
  14. And again, but in 2021, the article titled “New Trials on T3/T4 Combination for Hypothyroidism ‘Justified’“. It’s not the first time. But you always hope something will FINALLY stick. We as patients already know that we need T3, not just T4. When will the medical establishment catch up and quite lumbering along about this??
  15. From 2021, there are weaknesses in this article about combination therapy with T4 and T3. For one, it mentions studies which show non-effectiveness of T3 with T4. But we know very well it’s because they were going by the crappy TSH lab test and keeping patients underdosed. Even still, the article opens the door about the efficacy of T3 with T4.


  • DESICCATED THYROID IS A SAFE ALTERNATIVE Thanh D. Hoang, DO, staff endocrinologist of the Walter Reed National Military Medical Center in Bethesda, Md., told Endocrine Today at ENDO 2013. Note: though this study did conclude NDT is safe, the study was flawed. They went by the lousy TSH, keeping participants hypothyroid, and they didn’t understand the problems of low cortisol and iron effecting the good results of NDT, thus those preferring NDT would have been a lot higher.
  • A HEALTHY THYROID PRODUCES A ROUGH EQUIVALENT TO 3-5 GRAINS OF DESICCATED THYROID A few years ago, we found detailed medical info that revealed this, explaining why so many of us ended up in that range (tho not all). This article states: Estimates of average normal secretion for euthyroid humans are 94-110 µg T4 and 10-22 µg T3 daily (300). If you need more, it can be due to exogenous desiccated thyroid (giving it to yourself) vs. the superior absorption of natural release of thyroid hormones. Scroll down to slightly more than half way: (This used to be shown on the Thyroid Manager site, but they hide it now and ask for money before you can see it. So go here and you can download the article for free.)
  • COMPARING LEVOTHYROXINE TO NATURAL DESICCATED THYROID aka DTE Though this study clearly had problems (probably not raising high enough and/or going by the TSH), it did find that nearly 49% preferred desiccated thyroid. We have no doubt that figure would have been higher if the study understood what informed patients do about the use of NDT.
  • CONVERSION TO ARMOUR FROM LEVOTHYROXINE IMPROVED PATIENT SATISFACTION  From 2014, this research article was done by doctors Gary M. Pepper* and Paul Y. Casanova-Romero. That satisfaction would apply to move all NDT’s, not just Armour.  The efficacy included 30 subjects 65 yrs of age and older.


Study not only concludes how well NDT does for patients (mostly mentions the brand Armour, but applies to all NDT’s), it also underscores that it did well for participants 65 and over, contrary to the ridiculous warnings by misinformed doctors about anyone over age 60.


Check out this 2018 study which showed that having a higher serum FT3 was associated with lower risk of conversion to Alzheimer’s (AD), and those with the lowest serum FT3 had a “twofold increased risk of AD compared to those in the highest quartile. From Janie: Which is just another reason why none of us should be forcing ourselves for conversion alone on Synthroid or Levo, etc. We need direct T3 in our treatment AND to be optimal (which puts the free T3 towards the top part of the range)


  • LOW T3 CAN BE IMPLICATED IN DEATHS WHILE IN ICU In unselected ICU patients, FT3 was the most powerful and only independent predictor of ICU mortality among the complete indicators. Addition of FT3 to the APACHE- score could significantly improve the ability to predict ICU mortality.
  • T3 IS NOT ONLY ANTI-CANCER IN YOUR LIVER, BUT CAN HELP YOUR LIVER TO REGENERATE: From the American Association for Cancer Research, this research study shows that T3 can not only be anti-cancer, but actually help your liver to form new cells: COMMENT: This article shows that T3 REDUCES liver nodules, and you can wonder what T3 might do against cancer elsewhere in your body.
  • T3 IS BETTER FOR CRITICALLY ILL PATIENTS THAN IS T4: And there have been plenty of patient reflections when sick and forced to be on T4 in the hospital which confirms this!
  • At the 90th annual meeting of the Endocrine Society, June 2008, it was announced that T3 can be an effective substitute for T4. And�the target TSH was .5 — 1.5. Comment from Janie: Even though being on desiccated thyroid, with its T4, T3, T2, T1 and calcitonin, is even better according to the experience of many patients, this announcement is at least a good step in the right direction. Hopefully, they will take the final step!
  • Titled “Safety review of liothyronine use: a 20 year observational follow up study”, this article concludes there is “no increased risk of fractures or atrial fibrillation in patients taking liothyronine compared to L-thyroxine”…something we already know by years of experiences with T3. The article concluded that “There was an increased risk of mental health disorders if liothyronine was used alone.”…but not only is that erroneous, but implies that patients were not given enough T3, thus is was suppressing more than replacing.
  • T3 clearly helps the heart, not hurts it! “….therapy with physiological doses of T3 are safe and provide beneficial effects on ischemic heart disease.”


Stop the Thyroid Madness, based on years of patient reported experiences, was the first to recognize and state how important being optimal is. Now comes this remarkably cool article and research about the importance of being OPTIMAL Though some info is different than our experiences, it’s a HUGE step about the importance of optimal treatment, which is NOT about T4, not about the TSH:




This article outright points out a study which shows that “therapy with levothyroxine alone was not sufficient to induce a total remission of depressive symptoms in this population”. Plus…“In patients treated with T4, psychological symptoms may persist even when they achieve a euthyroid state.” Sadly, parts of the article are lacking…for example, it states “…the vast majority of patients with depression do not have biochemical evidence of thyroid dysfunction”. Clearly, they aren’t looking in the right places and probably going by the ridiculous TSH range, which can never show the lack of T3 in many tissues and organs including the brain!!


Dr. Peter Whybrow, a world-renowned expert on bipolar disorder, published his findings in the journal Molecular Psychiatry about the connection between thyroid and bi-polar. But it’s hard to find on the net. Instead, here is one of several other articles which talks about this connection:


This study, titled Antidepressant use and salivary cortisol in depressive and anxiety disorders reveals that antidepressants can drive cortisol too high or low.



We’ve always known that zinc lowers cortisol, and here’s a research article that underscores why:


We already knew this by many experiences. But here’s more research proof. So we take iron with it!


Finally, from Med Hypotheses. 2003 Aug;61(2):182-9….a mention of the connection, though it’s referring to thyroid hormone resistance, and patients who’ve had Fibro and saw it go away didn’t all have resistance. But it’s a great start and only underscores the brilliance that Dr. John C. Lowe gave us about the connection between hypothyroidism and fibromyalgia.

GENE VARIATION AFFECTS THE ABILITY TO CONVERT T4 to T3 IN SOME (i.e. justifying adding T3 to T4, or even better, using desiccated thyroid).

From the Journal of Clinical Endocrinology and Metabolism comes this article titled: “Common Variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients” May 2009,94(5):1623-1629.

Research conclusion: “Commonly inherited variation in the deiodinase 2 gene (DIO2 ) is associated with impaired baseline psychological well-being on T4 and enhanced response to combination T4/T3 therapy but did not affect serum thyroid hormone levels. A large patient study found that 16% of the study population had a variant DIO2 gene which impairs the ability of T4 to be converted to T3. Thanks to Terry for sending this!


From 1980 and the J. Clin. Invest. (The American Society for Clinical Investigation, Inc.), this article explains how the brain is affected by thyroid hormones, whether from excess or a deficiency, and talks about the deiodinase enzymes converting T4 to T3.


From 2010, and we can also surmise that if T4-only is leaving one hypo, it could also cause a raise in one’s blood sugar levels as revealed by the A1C for some. The A1C looks at one’s average level of blood glucose/blood sugar over the previous three months.


Though this article has the ridiculous “greater than 10” TSH as a problem (give me a break—how many of us have had a TSH in the 1’s or 2’s along with raging hypothyroidism), it at least underscores that higher cholesterol can go hand-in-hand with a hypothyroid state…and the latter includes being on T4-only, which leaves most with some form of hypothyroid symptoms.



  1. This PubMed article from 2005 is about research which shows that even suppressive doses of T4 do not negatively affect bone mineral density. And this one from 1993:
  2. The Society for Endocrinology in the UK in 2010 did research which revealed that having lower TSH levels while taking Thyroxine replacement is not detrimental to health, and that low level was .004 to .4 !! I also did a blog post about this here.
  3. This research is all the way back to 1972 and shows that the TSH is very sensitive to raises of T4/T3 to the point of becoming a subnormal/below range TSH. And we as informed patients have especially seen this below range TSH with raises of T3. And this subnormal TSH does not equal to high levels of the frees as does what happens with Graves disease/hyperthyroidism.


This was a short forum with comments by David Derry, Raymond Peat, and individuals: NOTE: the following link now fails to show the comments, but I’m leaving it to show it did used to exist. Hopefully we find the comments again. ( COMMENT: you can see the blossoming of doubt about the TSH in these posts from 1999 to 2002.


From 2021 comes this excellent article about the problems with solely going by the TSH and titled Managing the Total Thyroid Process: Written by Mel Rowe, Rudolf Hoermann, and Peter Warmingham

Written in 2005 in the The Journal of Clinical Endocrinology & Metabolism, this article says the evidence is compelling that the TSH range should be far more narrow, and it agrees with what Janie has said all along: that “reference populations previously considered normal were contaminated with individuals with various degree of thyroid dysfunction that served to increase mean TSH levels for the group”.


From Oct. 2016, this is underscoring how a so-called “normal” TSH doesn’t always equal the removal of hypothyroidism (and includes the problem of Levothyroxine).


From 2019, this timely article titled “Time for reassessment of the treatment of hypothyroid” underscore not only how damaging it’s been to rely on a single thyroid lab, but pays attention to patient complaints. I, Janie A. Bowthorpe, give a HUGE AND APPRECIATIVE THUMBS UP to

  • John E. M. Midgley
  • Anthony D. Toft,
  • Rolf Larisch,
  • Johannes W. Dietrich and
  • Rudolf Hoermann



From 1983, this medical article underscores that saliva testing is far superior to blood testing when it comes to cortisol levels. Order your own saliva cortisol test here.


Though this article is maddening the way it implies that the TSH lab is an ideal way to diagnose hypothyroidism (Hogwash!! Patients have had hypo with a TSH below 2!!), besides the way they say that you only have “subclinical hypo” if your TSH is up to 10 (give me a break!), it does come to a conclusion that patients already know: hypothyroidism raises cortisol! (which eventually turns into low cortisol—see the last chapter in the STTM II book!). And of course, they don’t realize that this is what happens to so many on the inadequate T4-only!!


Great study which reveals that “salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery”….and “the elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.


This study explains the circadian rhythm of cortisol and is why we dose ACE or HC (if saliva proves we need either) similarly i.e. most in the morning and less each time: “cortisol levels reach lowest levels at around midnight, levels start to rise at around 02:00 to 03:00 and reach a peak at around 08:30. Cortisol levels then slowly decrease back to the nadir to complete the cycle over 24 h.”


This study explains the effects of phosphatidylserine on endocrine response to moderate intensity exercise. i.e. it can also help us lower high cortisol, even from having had poor thyroid treatment, or the stress after thyroid removal, etc.

f) RAISING POTASSIUM CAN RAISE LOW ALDOSTERONE : From this book page called Endotext [Internet]:,angiotensin%20II%20infusion%20(12), and the heading Aldosterone Deficiency and Resistance, see this: Potassium directly increases aldosterone secretion by the adrenal cortex and aldosterone then lowers serum potassium by stimulating its excretion by the kidney. High dietary potassium intake increases plasma aldosterone and enhances the aldosterone response to a subsequent potassium or angiotensin II infusion (12). The primary action of potassium for stimulating aldosterone secretion is to depolarize the plasma membrane, which activates voltage-dependent calcium channels, that permit influx or efflux of extracellular calcium (1214), leading to the activation of calmodulin and calmodulin-dependent kinase, subsequently. The activated kinase phosphorylates both activating transcription factor and members of CRE-binding protein family which bind to 5’ flanking promotor regions of the CYP11B2 gene and trigger gene transcription in the zona glomerulosa, followed by increased aldosterone biosynthesis (13,14).


From the Oct. 2008 issue of the Journal of Clinical Endocrinology and Metabolism come this article which states people with celiac disease had a greater than fourfold increased risk of being diagnosed with hypothyroidism, a threefold increased risk of suffering hyperthyroidism, and a 3.6-fold increased risk of developing thyroiditis.

RESEARCH VALIDATING THE IMPORTANCE OF T2, aka 3, 5-diiodothyronine (which you get in desiccated thyroid!)

The accumulated evidence permits the conclusion that the actions of T2 do not simply mimic those of T3 but instead are specific actions exerted through mechanisms that are independent of those actuated by T3 and do not involve thyroid hormone receptors. In addition, very recent evidence leads us to suggest that T2 may be a potentially useful agent for the treatment of diet-dependent overweight (and the consequent hypertriglyceridemia and high cholesterol level) without inducing thyrotoxicosis.


The following link takes you to a website with a study of pregnant women with “normal” TSH, but who are positive for antibodies, who have fewer miscarriages following thyroid treatment. Medscape requires a log-in, but it’s free, and it sends regular e-mails on the latest research according to your preferred topics. COMMENT: Once again, this article proves that a so-called normal TSH means squat, and miscarriages can have a strong connection to your undiagnosed or undertreated hypo state.


Many studies have been coming out about the connection, and especially as related to your iodine levels. Here is one titled from 2003 “The thyroid, iodine and breast cancer” from Breast Cancer Res and PubMed. plus “Breast Cancer in Association with Thyroid Disorders” From 2009:


This research explains how insufficient T4 and T3 can affect hair follicles.


Yup, this is a real live article title from the European Journal of Endocrinology, Oct. 6, 2009. And patients on desiccated thyroid can shout a resounding YES, YES, YES! We know the truth. When are you? Comically, the beginning of this article states that “10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with T4 explains remaining complaints.” NOT. The rest is good.

See this Big Daddy of references from Thierry Hertoghe, MD of Belgium.

**AND FINALLY: totally RIDICULOUS JOURNAL ARTICLE that treatment shouldn’t even occur until the TSH is at LEAST 10. Are you kidding me?? I was miserable at 5 when my hypo was first discovered:

A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because it opponents eventually die, and a new generation grows up that is familiar with it ~ Max Planck

Important note: STTM is an information-only site based on what many patients worldwide have reported in their treatment and wisdom over the years. This is not to be taken as personal medical advice, nor to replace a relationship with your doctor. By reading this information-only website, you take full responsibility for what you choose to do with this website's information or outcomes. See the Disclaimer and Terms of Use.