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Does Thyroxine Therapy Harm Euthyroid Patients?

Updated: Apr 12, 2023

Written by Dr. John C. Lowe on his platform Thyroid Science, with questions and answers.


June 20, 2010

Question: I am a general practitioner in the UK. Many of my patients have told me that they recovered from their hypothyroid symptoms after they found a private doctor who treated them with thyroxine despite their normal TSH levels. These patients had been denied thyroxine treatment by doctors within the National Health Service because of their normal TSH levels. So many patients have told me this that I have developed reservations about ruling out hypothyroidism and the need for thyroxine therapy based on a normal TSH test.

Many more of my patients with normal TSH levels ask me to prescribe thyroxine or Armour Thyroid. I am hesitant to comply because of the Royal College of Physicians' statement about adverse effects from unnecessary thyroid hormone therapy. May I have your point of view on the potential for adverse effects from thyroxine treatment when patients do not actually need it?

Dr. Lowe:

I'm familiar with the statement you refer to by the Royal College of Physicians. Specifically it is: ". . . some patients are inappropriately diagnosed as being hypothyroid (often outside the NHS) and are started on thyroxine or other thyroid hormones which will not only cause them possible harm . . ." (Italics and bold mine.)

Like too many other statements or implications by the Royal College of Physicians, when applied to the general population, this one is patently false.

Unless you're a geriatric specialist whose patients are among the most fragile of human beings, even if they don’t need supplemental thyroid hormone, a trial of thyroid hormone therapy is harmless. If the hormone doesn’t help them, you can wean them off it and then have them stop it altogether. No harm done!

Proof of this is in the history of FDA-guided studies of the potency and stability of T4. To test T4 for potency and stability, researchers—using FDA test guidance!—have traditionally used volunteers who were "euthyroid," meaning, of course, that they subjects had normal thyroid function test results. Moreover, FDA test guidance has allowed researchers to use euthyroid volunteers to test higher-than-physiological (supraphysiologic) doses of T4.[1,p.109]

I ask the Royal College of Physicians: If it were likely to harm euthyroid volunteers, why would FDA-test guidance allow researchers to use them for the testing? And why would institutional review boards approve the studies as not potentially harmful to the volunteers?

The answer is simple, of course: A trial of thyroid hormone therapy—even for people with perfectly normal thyroid function—is harmless, even when they use supraphysiologic doses. Only recently have researchers suggested that rather than testing euthyroid volunteers, they would best use thyroidectomized patients. But the researchers' reason for this suggestion has nothing whatever to do with any harm ever done to euthyroid volunteers in the studies. The testing hasn't harmed the euthyroid volunteers, nor will a trial of thyroid hormone therapy harm practically any of your euthyroid patients except possibly the most severely fragile of them. But, then, a cup of coffee is just as likely to harm those fragile folks.

I just don't understand something: How does the Royal College of Physicians (as with this particular issue) and the British Thyroid Association make scientifically false statements and stand by them in the face of proof that they are false, yet receive no official reprimands from regulatory authorities in the UK? To me, their false statements are an affront to the noble tradition of science, and the organizations sticking by their false statements in the face of refuting evidence reduces the statements to examples of pseudoscience.

At any rate, I hope this reply is helpful to you in providing your patients with harmless trials of thyroid hormone therapy, whether they truly need it or not. References 1. Royal College of Physicians. The diagnosis and management of primary hypothyroidism. 2008. 2. Eisenberg, M. and DiStefano, III, J.J.: TSH-Based Protocol, Tablet Instability, and Absorption Effects on L-T4 Bioequivalence. Thyroid, 19(2):103-110, 2009.

(This Q&A was published simultaneously at


June 12, 2010

Question: I have a hypothesis paper that I’m considering submitting to Thyroid Science. I’m hesitant, however, because there may be advantages to publishing in major medical journals, such as the Journal of the American Medical Association. Of course, I may have a harder time getting my paper accepted because of competition. What are your thoughts for people who are new to submitting papers to journals? Can I submit my paper both to Thyroid Science and another journal and go with which ever journal accept it?

Dr. Lowe:

Many people have asked us this same question. Of course, we would like a chance to publish your paper if our reviewers believe it has merit in the field of thyroidology. However, if your paper may contribute to changing the current “T4 replacement paradigm” for hypothyroidism, we really don't care which journal first publishes it, as long as you get it published.

To some, that policy may seem self-sabotaging toThyroid Science, but it really isn't. If we feel that a paper published elsewhere is important enough, we'll ask the author(s) to write a summary of the paper for our journal, possibly further articulating the thesis and providing more supporting evidence. And if the author won’t cooperate, we may compose a paper based on the author(s)' that provides the important information for our readers.

In deciding where to submit your paper, you might keep in mind a few points I wrote to another potential author this morning. What I wrote to him is essentially the following.

Long ago, when I was being educated in research psychology (I think Galileo sat two rows in front of me), I took courses that dealt with the ethics of scientific conduct. We were taught that it's unethical to publish exactly the same paper in more than one journal, even if years have passed since the first publication. That policy is an old one, and it still applies. Because of this, you should submit your paper only to one journal at a time. If the first journal rejects your paper, then, and only then, submit it to the next one.

If you want to spread your hypothesis wider than one journal would allow, you can easily do that. First, publish your paper in one journal, and write as many otherpapers as you want for other journals. This is perfectly ethical as long as your other versions of your paper are indeed other versions; that is, in subsequent papers, you should express your hypothesis exactly as it was originally published, but in different terms. Expressing the same thoughts in different terms is ethical. In my view, in fact, if you feel that your hypothesis can lead to the relief of suffering of human beings, you have a humanitarian responsibility to publish it as many times as needed to accomplish that worthy end.

If you can get your paper accepted by a major traditional print journal, you'll have some important advantages. For example, you're likely to have more prestige in the eyes of the typical practicing conventional clinician, and your paper will be included in the traditional major indexing systems, such as Medline.

On the other hand, the print journal may fail to publish your paper in an open-access electronic version of the journal. If so, only those who subscribe to the print version of the journal are likely to read your full paper. As time passes, the only part of your paper that most interested people will have access to will be the abstract that is online. They can access your abstract through most search engines, such as Google and Yahoo.

Otherwise, if anyone is interested enough in arrange to get a copy of your full paper, he or she will have one of two options: First, he or she can buy a copy online from the closed-access journal. This can be expensive, and it can be prohibitive if one does a great deal of journal research. Second, he or she can travel to a medical library, track down your paper in a bound volume of all the papers published in that journal during the year, and photocopy it. This option is inconvenient for most people. This may account for me seeing in recent years fewer and fewer people in medical libraries copying journal papers.

Another downside of traditional print journals is something that frustrated many of us who used to publish in traditional print journals: the “publication lag.” I know of some journals that had a lag of two years. This meant that by the time one’s paper was published, it was more history than news. Because of the publication lag, I encourage you talk or write to an editor of the journal you decide to submit to. As whether in addition to publishing a print version, the journal will also rapidly publish an electronic version online.

Another important issue is whether the journal is available only to subscribers ("closed-access") or is "open-access." Open-access means that most publications in the journal are free to read without a subscription. Steadily more open-access journals are being published, and they are impacting traditional print journals. When I've inquired, medical librarians, who work where traditional print journals are stored, have told me, “open-access journals are killing us.”

One advantage of electronic publishing, especially in open-access journals such as Thyroid Science, is that we have virtually no publication lag. We publish papers are rapidly compared to print journals. In addition, with open-access journals, anyone in the world with access to the Internet can find and read your paper using Google, Yahoo, or most any other search engines. One doesn't even need to use Medline, PubMed, or any of the other traditional indexing system. In fact, I believe these systems are on the verge of being obsolete. Most search engines such as Google also index the papers that formerly were indexed only in the traditional indexing systems. Plus, Internet search engines also indexes publications not included in PubMed.

If you publish in another journal for whatever advantage, we fully support you in it. And if you'll send us an advanced copy of your paper, after the other journal publishes it, we may ask you to summarize your hypothesis and elaborate on it in a second paper for Thyroid Science.

Best of luck in getting your hypothesis published, wherever you decide to submit your paper.


November 24, 2009

Question: My doctor gave me my lab results yesterday. I know what most of the thyroid tests are, but I’ve never heard of one. It is the “prealbumin.” Do you know what this is? My level was 0.20 g/L, and the range is listed as 0.18-to-0.39 g/L. Do you know what this result means?

Dr Lowe: We have a newer name for prealbumin, which is “transthyretin.” Transthyretin is a protein that is important to thyroid hormone regulation of the brain. The protein transports thyroid hormone across the blood-brain barrier; that is, from the blood outside the brain to the blood inside brain. Transthyretin that ransports thyroid hormone in the blood is produced in the liver, but transthyretin that transports thyroid hormone across the blood brain barrier is produced in a structure called the “choroid plexus” at the base of the brain.

When I say that the protein transports thyroid hormone across the blood-brain barrier, I mean that it transports both T4 and T3. This is important to understand. The reason is that many clinicians mistakenly think that transthyretin transports only T4 into the brain. Based on this mistaken belief, these clinicians also mistakenly believe that normal brain function depends on patients including T4 in their thyroid hormone therapy. This, however, is patently false. (Elsewhere, I extensively documented that transthyretin transports both T4 and T3 into the brain. I published one article in 2005 and the second in 2006.)

You wrote that your transthyretin level was 0.20 g/L (20 mg/dL). With a range of 0.18-to-0.39 g/L (18-to-39 mg/dL), your level is very low; it’s in the lower 4th of the range.

Some diagnosticians would say this level means you’re not producing an optimal amount of transthyretin; others would say that you’re producing plenty. I don’t think we have enough studies to tell us which of those diagnosticians are right and wrong.

What we can tell from your level is that you’re producing the protein and your most likely getting thyroid hormone into your brain. We don’t have tests commercially available that measure the amount of thyroid hormone that is bound to one’s transthyretin. That piece of information would be valuable. The reason is that dioxins and PCBs can displace thyroid hormone from the protein. As a result, these chemical contaminants can ride into the brain on the protein. The more of the contaminants that ride the protein into the brain, the less T4 and T3 are likely to reach brain cells. Once inside the brain, dioxins and PCBs bind to T3 receptors on genes. The binding alters the pattern of codes that the genes send out to the work part of the cell for the production of proteins. I believe this phenomenon is responsible for some of the cognitive and mood problems of people contaminated with dioxins and PCBs, which toxicologists have told me is each of us. (I heavily documented the thyroid-disrupting effects of these pollutants in the “Environmental Contaminants” section in Chapter 2.4, “Thyroid Hormone Deficiency,” of The Metabolic Treatment of Fibromyalgia [available in the publisher's E-Chapter section].)

I assume that you wrote to me about your transthyretin level from concern about your thyroid hormone status. However, some clinicians order the test to learn whether a patient is ingesting enough protein. Transthyretin is a “glycoprotein,” which means it is a carbohydrate combined with a protein. Of all the proteins in the blood, it’s transthyretin that is most useful in telling whether a person has a protein deficiency. The half life of the protein is about two days, so it’s level in the blood changes quickly when someone markedly decreases or increases protein intake, digestion, and/or absorption.

You didn’t say whether you ate little to no protein for several days before your blood was drawn to measure your transthyretin. If you ate little to none, that might account for your low-range transthyretin level. If that is the case, you should talk with your clinician about measuring your transthyretin level again after you eat 50-to-75 grams of protein each day for several days. Your tranthyretin level might then be higher. But keep in mind that inflammation and infection can also lower transthyretin level, and severe kidney disease and the use of glucocorticoid (such as prednisone or prednisolone) can raise your level. I hope this is helpful to you.


December 8, 2008

Question: I'm so thankful I was told about I read the article on "Weight Gain and the TSH" and sent it to my three sisters who also suffer from hypothyroidism. I started the Armour Thyroid medication almost two weeks ago and feel so much better than the last 7 years of being on levothyroxine. I know this is a positive start in the right direction for me personally. I have 30 pounds to get rid of that I've gained in the last 7 years after two consecutive pregnancies in 2002 and 2003. Thank you for making this information available to the people (not just doctors) who are pro active about their health.

Dr Lowe: Thanks so much for writing about feeling better on Armour Thyroid after gaining thirty pounds of weight while on levothyroxine. If you use a high enough dosage of Armour, I expect that you’ll lose the 30 lbs you gained over the seven years that you used levothyroxine. This is especially likely if you have a wholesome diet and regularly exercise to tolerance.

Armour Thyroid, like Nature-Throid and Westhroid, is more effective than levothyroxine at reducing body fat. The reason is that these products contain T3. Some researchers say that T3 has a “lipolytic”—that is, a fat-decomposing—action in fat cells.[3] One way T3 reduces fat in the cells is by inhibiting an enzyme (cyclic-AMP phosphodiesterase) that slows down metabolism shortly after adrenaline and noradrenaline speeds it up.[1][3][8] By blocking this enzyme, T3 sustains the fat-decomposing effect of adrenaline and noradrenaline in fat cells.[1][2][8]

Another way T3 reduces fat is by altering gene transcription for several compounds. When T3, acting through the relevant genes, increases fat cells’ production of these compounds, the compounds augment adrenaline’s and noradrenaline’s fat-lowering effect in the cells.[10]

In addition to weight loss, you may get another benefit from the T3 in Armour: that is, a reduction of fat that probably accumulated in your arteries[3] while you were on T4 replacement. As Duntas wrote,[11] As Duntas noted in 2002, the composition and transport of blood fats “are seriously disturbed in thyroid diseases.” Among patients with an high TSH and low thyroid hormone levels, cholesterol and LDL are typically high.

Even when thyroid hormone levels are within the reference range but the TSH is high, patients on average have a slightly high total cholesterol, high LDL, and low HDL. These patients also have abnormalities of the linings of arteries, inflammation and fat accumulation in the aorta, and they are subject to have myocardial infarctions. They also have increased resistance to blood flow, weaker contractions of the heart muscle, and increase diastolic blood pressure. As Duntas pointed out, thyroid hormone therapy—especially with TSH-suppressive dosages—“usually leads to a considerable improvement in the lipid profile.”

T3 reduces fat in artery linings in part by increasing the activity of an enzyme called “lipoprotein lipase.”[4] Low activity of this enzyme leads to high blood fats, which is a risk factor for coronary heart disease.[7] Thyroid hormone increases the activity of the enzyme, and by doing so, it reduces blood fats.[4] Thyroid hormone also lowers LDL cholesterol by increasing the number of LDL receptors on liver cells.[11]

In my clinical experience, thyroid hormone therapy (with products that contain T3) is by far more effective than statin drugs in normalizing blood fats. I believe that if patients in general were allowed to use effective thyroid hormone therapy rather than T4 replacement, we could virtually eliminate the market for statin drugs. Then patients would be free from the potential adverse effects of statin drugs, such as chronic muscle pain and other pain syndromes, elevated liver enzymes, peripheral neuropathy, and muscle damage.[9]

Please let us know how you progress. I wish you the best for losing the weight you gained while on levothyroxine.

References 1. Bégin-Heick, N. and Heick, H.M.: Increased response of adipose tissue of the ob/ob mouse to the action of adrenaline after treatment with thyroxin. Can. J. Physiol. Pharmacol., 55(6):1320-1329, 1977. 2. Elks, M.L. and Manganiello, V.C.: Effects of thyroid hormone on regulation of lipolysis and adenosine 3',5'-monophosphate metabolism in 3T3-L1 adipocytes. Endocrinology, 117(3):947-953, 1985. 3. Mandel, L.R. and Kuehl, F.A., Jr.: Lipolytic action of 3,3'5-triiodo-L-thyronine, a cyclic AMP phosphodiesterase inhibitor. Biochem. Biophys. Res. Commun., 28(1):13-18, 1967. 4. Pykälistö, O., Goldberg, A.P., and Brunzell, J.D.: Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism. J. Clin. Endocrinol. Metab., 43(3):591-600, 1976. 5. Beisiegel, U.: Lipoprotein metabolism. Eur. Heart J., 19 Suppl A:A20-A23, 1998. 6. Otto, W., Taylor, T.G., and York, D.A.: Glycerol release in vitro from adipose tissue of obese (ob/ob) mice treated with thyroid hormones. J. Endocrinol., 71(1):143-155, 1976. 7. Salter, A.M. and Brindley, D.N.: The biochemistry of lipoproteins. J. Inherit. Metab. Dis., 11 Suppl 1:4-17, 1988. 8. Wahrenberg, H., Wennlund, A., and Arner P.: Adrenergic regulation of lipolysis in fat cells from hyperthyroid and hypothyroid patients. J. Clin. Endocrinol. Metab., 78(4):898-903, 1994. 9. Brown, W.V.: Safety of statins. Curr. Opin. Lipidol., 19(6):558-562. 2008. 10. Viguerie, N., Millet, L., Avizou, S., et al.: Regulation of human adipocyte gene expression by thyroid hormone. J. Clin. Endocrinol. Metab., 2002 Feb;87(2):630-634, 2002. 11. Duntas, L.H.: Thyroid disease and lipids. Thyroid, 12(4):287-293, 2002.


November 16, 2008


Has the paper below really been reviewed????

I do not question the Lowe thesis, but I believe that a poor paper to support it is in fact harming the cause—especially if the methods used are not backed up with known or accepted methods.

Dr Lowe: Thank you for your email and your thoughts. Yes, indeed: Dr. Øverbye’s paper was reviewed. Several of our peer reviewers read the paper, and each strongly recommended that we publish it. As one of the reviewers commented after critiquing Dr. Øverbye’s manuscript, “This paper reports the type of cutting-edge, creative pilot research that we want to encourage.”

You suggest that Dr. Øverbye’s paper is "poor" because his methods were "not backed up with known or accepted methods." In conventional medicine, of course, creative research using innovative methods has traditionally been resoundingly discouraged. Recall the dictum, “Be not the first by whom the new is tried, nor the last to lay the old aside.” We at Thyroid Science reject this progress-stifling, herd-mentality orientation. Instead, we encourage originative and progressive clinical methods and research. That orientation is exemplified by Thyroid Science publishing Dr. Øverbye’s paper. As objectionable as this orientation may be to some people within conventional medicine, we steadfastly stand by it, as we believe this orientation is likely to bring help to millions of thyroid patients whom conventional medicine continues to fail.

Your assessment of Dr. Øverbye’s study and his paper brings to mind similar notable occurrences. They involved Professor Linus Pauling, a two-time Nobel Prize winner ranked among the ten most fruitful scientists in history. Pauling was also fruitful in his scientific investigations in the field of nutrition. But editors of medical journals often censored him by rejecting or delaying publication of his manuscripts because the contents challenged conventional medical prejudices. (To read his description of the censorship by editors—including the editor of the Journal of the American Medical Association—read his chapter titled “Organized Medicine and the Vitamins” in his book for the public titled How to Live Longer And Feel Better.)

By contrast, after some resistance early in his career, chemistry journals accepted Pauling’s thinking and methods that were clearly beyond the boundaries of “the box.” Some editors accepted his manuscripts containing extremely innovative material without sending them to peer reviewers. As one editor noted, peer reviews were impossible in that Pauling had no peers. The chemistry profession got the benefit of Pauling’s imaginative and innovative mind. But censorship of this scientific genius protected from refutation the presumptions and prejudices of the editors, commercial sponsors, and readers of some medical journals.

I’m not saying that Dr. Øverbye’s paper is certain to have the gargantuan scientific importance of many of Pauling’s papers (although I'm also not saying it won't). What I am saying is that Thyroid Science will not censor research simply because it involves thoughtful, fresh ideas, and innovative methods. As in Dr. Øverbye’s case, we encourage researchers to use well-established technologies from other fields to make scientific advancements in the field of medicine. He has done this, and admirably so.

We appreciate you expressing your opinion and prompting us to explain why our reviewers and editors enthusiastically accepted Dr. Øverbye’s paper for publication.


February 23, 2008

Question: Are you aware of the paper by E Tjørve, KMC Tjørve, JO Olsen, R Senum, H Oftebro titled "On commmonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity in peripheral tissues" (Medical Hypotheses, (2007) 69, 913-921)? In it the authors call for a test for peripheral resistance. Since the standard thyroid function blood tests don't serve this purpose. which of course the standard thyroid function blood tests don't. Maybe the fine-needle aspiration (FNA) technique used by Dr Bo Wikland and his colleagues would fit the bill?

Dr Lowe: I have read the E Tjørve paper. I was pleased that Dr. Tjørve and his coauthors mentioned measuring the basal metabolic rate as a method for testing for resistance. I have used the test in my clinical practice for several years and published two studies so far using the method:

Report at Medical Science Monitor: (When you reach the page at Medical Science Monitor, scroll down to the second paper under "Clinical Research".) Report at Thyroid Science:

Along with Tjorve et al, I believe that the basal or resting metabolic rate measurement is most useful clinically for identifying resistance patients, at least those with peripheral resistance. (Having peripheral resistance, of course, means that a patient's pituitary gland is normally or almost normally responsive to thyroid hormone, but most tissues peripheral to the pituitary are partially resistant.) Dr. Wikland’s FNA identifies patients who have autoimmune thyroiditis despite reference range antithyroid antibody levels. Most of the patients are hypothyroid, which is the reason he and his colleagues term the disorder “subchemical hypothyroidism.” Some of these patients may also have peripheral resistance. But if they improve or recover with doses of thyroid hormone that are lower than supraphysiologic amounts, that would indicate that they are only hypothyroid and not resistant. Most thyroid hormone resistance patients have to use supraphysiologic dosages of T3 to get well. Even T4/T3 products such as Armour usually don't work for them, not unless they use huge dosages, such as 12 grains or more. I have a book published in 1962 written by an endocrinologist—an endocrinologist from the time when many of them practiced clinical medicine rather than the extremist technocratic medicine of most endocrinologists today. In the book, the endocrinologist wrote that some of his “hypothyroid” patients didn't recover until they took as much as 60 grains of desiccated thyroid per day. I assume those patients really had peripheral resistance, as that amount would contain roughly 540 mcg of T3. That's truly a supraphysiologic daily dosage! As I have, Dr. Wikland has found that most hypothyroid patients must suppress their TSH levels before they recover. I don't know the dosages his patients typically use, but if some of them use dosages that are well into the supraphysiologic range, the patients are probably partially resistant to thyroid hormone. I use the following criteria to diagnose peripheral resistance: the patient has before treatment

(1) hypothyroid-like symptoms before treatment,

(2) reference range TSH and thyroid hormone levels, and

(3) an abnormally low resting metabolic rate; and after treatment, he or she

(4) recovers from his or her symptoms with a supraphysiologic dosage of plain T3

(5) with no evidence of thyrotoxicosis. There are laboratory methods for testing for resistance. For example, we can use fibroblasts from a patient’s skin. If a supraphysiologic amount of T3 is needed to inhibit the fibroblasts' synthesis and secretion of connective tissue constituents such as fibronectin, then the patient's cells (at least his or her fibroblasts) are resistant to thyroid hormone. I don’t use this particular test for two reasons: first, it isn't available commercially; and second, even if it was, it requires a painful punch biopsy of the skin that I would prefer not to subject patients to.

To sum up, Dr. Wikland's FNA can certainly identify patients who are hypothyroid due to autoimmune thyroiditis. However, the procedure would not identify or rule out peripheral resistance to thyroid hormone.


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