Tag Archives: T3

Endocrinologists Take a Backward Step in the Treatment of Hyperthyroidism

When I became an endocrinologist in 1981 I was truly excited about the field. At that time it seemed that the science of endocrinology was expanding rapidly and new discoveries were on the horizon particularly in regards to the way hormones effect the brain, mood and the immune system. Was I ever wrong! It’s thirty years later and none of those expectations were realized. In fact, I find that the field of endocrinology has barely budged since then and in some areas has actually lost ground.

Bringing on this round of pessimism on my part, is a recent “development” in the area of treatment for hyperthyroidism (over active thyroid). Ever since I was in training there have been two medicines, propylthiouracil (PTU) and methimazole (Tapazole), which are the mainstays of medical treatment for hyperthyroidism. Both medicines have been available since the 1940’s and show excellent efficacy and tolerability (and they are cheap!). Almost all endocrinologists I have met use these two drugs interchangeably although in pregnancy propylthyiouracil is favored due to rare birth defects in fetuses exposed to methimazole.

The “development” which I find so discouraging is the recent action by the FDA to place a very strict (black box) warning on the use of PTU due to the possible occurrence of a rare form of liver injury attributed to the drug. After almost 70 years of exemplary use, this has given rise to extensive debate in the endocrinology literature about how to restrict PTU use.

While it is true that methimazole is equally as effective as PTU to treat hyperthyroidism, I have personally seen numerous cases of fairly severe allergic reactions to methimazole. Fortunately it has been easy to continue medical treatment by simply switching to PTU. If we can’t use PTU freely then the only other options are surgical removal of the thyroid or eradication of the thyroid using radioactive iodine, neither of which is free of potentially adverse outcomes.

I have never encountered severe liver injury with PTU nor has any of the colleagues I have polled. It has to be very, very rare. This is obvious because it has taken 70 years to get around to recognizing it formally. Can we really call it progress that we now have one less simple option for treating hyperthyroidism, a common and relatively benign disease? Let me take my cynicism to the next level. I won’t be surprised if a major pharmaceutical company soon announces the development of a new drug for treating hyperthyroidism. If I’m right the new drug will add nothing of real value that wasn’t previously available but is many times more expensive then the drug it replaces.

So goes endocrinology into the new century, the stogy old lady of medicine.

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Suzi’s Amazing Blood Pressure Response to Cytomel (t3)

Suzi has hypothyroidism and high blood pressure. She sends the following story describing how t3 treatment appeared to help normalize her blood pressure. This is the first time I have come across this effect and thought it would be helpful to share her story on the main blog. Does anyone else have a similar (or contradictory) experience?


Hi Dr. Pepper,

I was diagnosed hypothyroid 2 years ago and given levothyroxine. On diagnosis I had lots of symptoms and my BP was 175/115 despite my whole family having low BP. After some months on T4 I did feel an improvement in a lot of ways and my BP got better. Then after a year, things started going wrong, as if my body didn’t like T4.

I tried reducing my dose of T4 back down to 75µg but went hypo. But each time I increased above 75µg my BP increased again, then on 112µg it became a serious problem, especially the diastolic. I still had fatigue, constipation, red eyes, swollen legs and so on.

About 3 weeks ago I started on 10µg T3 and reduced my T4 from 112 to 75µg and pretty much immediately felt clearer headed and more energy, the constipation went etc….. My BP has gone down by an average of 20, which I know because I check it regularly myself. I’m doing a 24-hour BP monitor this week too, because my doctor put me on Amlopidine 6 weeks ago after being shocked by the monitor results from then while on 112µg T4 (only took Amlopidine for 2 weeks after terrible side-effects incl. overwhelming fatigue and massively swollen legs).

So, it looks as though my body goes weird on T4 tablets when the dose is above 75µg, but if I stuck to that dose I’d be really hypothyroid. The T3 has changed my life completely!!

Now I’m wondering what the ideal balance T4 / T3 tablets would be? Is that possible to say or does it depend on each individual body and genetics? My typical BP now is around 120/ 95; it goes down after eating, and gets worse when I’m hungry or tired. The T3 reduced my BP so much more than the Amlopidine did, and on T3 I feel great whereas on Amlopidine I felt half dead. I’d like to get my BP back to before I got hypo, so that’d be 110/70.

All I need to do now is find my ideal dose of T4 and T3, could you possibly advise me on that? If I started 20µg T3 instead of 10µg, would you advise a reduction in T4 from 75µg? ( I’ll be doing a TSH, fT3 and fT4 test in about 5 weeks’ time, maybe I should wait till then?).

Thank you so much!

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What You can Learn from Sarah’s Struggle With Hypothyroidism

Every so often I like to bring attention to someone who has struggled to get properly treated for hypothyroidism. Not everyone shares the same dilemma regarding treatment of hypothyroidism because T4 by itself may be sufficient in many instances. But for those who continue to experience symptoms of hypothyroidism despite T4 treatment, adding T3 can be a life changing experience.

Here is Sarah’s story:

I was diagnosed with hypothyroidism in my early twenties and Synthroid did not help. I did not know at the time that many of my symptoms were due to hypothyroidism. After changing to my long time physician, I told her of my original diagnosis some years back. She did only the TSH and told me I was no longer hypothyroid! So for some 15 years after being in her care and continuing to feel crummy, then for the last 8 steadily gaining weight and feeling worse, I was not on any medication. I begged her for Cytomel several years back and was denied…she said she didn’t treat with that. When I finally was deemed hypo by her, she put me on the smallest dose of levothyroxine. It did not help. I finally went to see a shrink and he put me on 25 mcg of Cytomel. For the first time in my post pubescent life, I feel like living. My dose was upped to 50, and I felt even better but my thyroid levels were off, so we are now working on that and I am back to 25 mcg per day. If you can’t get Cytomel from your regular physician, you might get a psychiatrist to prescribe it. It changed my life and I finally feel alive. I’ve since switched primary physician because she wouldn’t listen to me, and she didn’t like that I was on Cytomel. I don’t know what it is about this medication that regular physicians don’t like and make them refuse to treat with it, especially when so many can benefit from it. I’ve lost only 12 lbs since being on it, but I gained nearly 35 unnecessarily while not being properly treated and was told to eat less and exercise more…I only ate about 1500 calories a day and walked my dog 2 miles each day, so I don’t feel it had anything to do with my diet!

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Cami Gets Contentious About the HCG Diet

The HCG diet has created a great deal of controversy among experts and the people who have tried it. Cami posts these words of warning about the HCG diet based on her own and her husband’s experience.

Cami writes:

What Dr. Simeons book does not tell you is that there is a good chance your hair will fall out aproximately three months after completing the 500 calorie phase of the diet. He also doesn’t mention that the shock to your system can cause adrenal fatigue, and hypothyroidism if you were already prone to these conditions.

My husband and I both went on the hCG diet and both lost the weight we had been hanging onto for years. I followed the diet perfectly, but as soon as the hCG stopped, the weight began coming back on, FAST! I had to do a steak day every other day, my blood sugar plummeted and I began to feel awful! I suffered fatigue, dry skin, dry mouth, no energy, no libido, and my muscles and joints began to hurt. The carb and sugar cravings were so intense I felt like a drug addict. I gained all the weight back plus 13 lbs. in three months, then the hair began to fall. My doctor was shocked and completely surprised. His only theory is that the usual dose wasn’t enough for me and I triggered a starvation response which affected my thyroid and adrenals. Together we are going to support adrenal health, then begin t3 therapy in an effort to repair my thyroid. My husband on the other hand, feel great! He has been able to keep off the weight, add some muscle and is happy and energetic every day. hCG does work, but if you have any health problems related in any way to the hypothalmus, I would consider taking the weight off very slowly to avoid starvation response.

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What is My Correct Thyroid Dose?

Lots of members at metabolism.com with hypothyroidism ask what is their correct thyroid hormone dosage. For those who are still confused I am posting the latest Q and A addressing this issue.

Member ecchho received radioactive iodine for hyperthyroidism (over-active thyroid) and as commonly happens, developed hypothyroidism (under-active thyroid). Despite t4 levels which appear to be normal symptoms persist, so ecchho inquires about ways of dealing with this common problem.

Here is the Q and A regarding ecchho’s post:

Hi Dr. Pepper:

I had Graves disease at 23 and then had RAI at 28 and have been on synthroid for 18 years. I did try ARmour once, but I found it had too much t3 (I think the pig’s ratio of t4 to t3 is much more potent than humans) and I actually had a real hard time regulating. I don’t have a thyroid anymore, and I take 225 synthroid. i still suffer a bit with impossible weight loss (despite running, dieting, etc) and some depression that feels quite hormonal at times. My dr. brought up adding t3 last visit and tested me, and then said, oh, you don’t need any xtra t3, you seem to be converting fine.
what are the levels that the t3 should be, and is this free t3 or t3? thanks.

My reply to Ecchho’s post:

Your question regarding the correct level for thyroid functions, is frequently raised on this website. I would respond to your question with this question, ” What is the correct shoe size?” Obviously, the answer is, whatever shoe size fits best. Similarly with thyroid function, everyone has a different “comfort zone” where their body functions best. That is their “correct” thyroid hormone level. You also refer to a t4 to t3 ratio for pigs versus humans. These ratio’s are averages of several hundred individuals (human or pig)and do not apply to any particular individual. Some people function better at a t3 to t4 ratio which is higher than the average. As pointed out in my article,http://www.metabolism.com/2009/11/07/breakthrough-discovery-thyroid-hormone-therapy-part-2/ , there is recent evidence that due to genetic differences, a percentage of the population does not convert t4 to t3 efficiently and therefore are likely to require t3 supplementation when treated for hypothyroidism.

Rather than spend the money for genetic testing to discover whether the genes for conversion of t4 to t3 are abnormal, some doctors recommend simply adding an appropriate dose of t3 to the standard t4 (levothyoxine)treatment and following the patient for improvement in clinical symptoms. You might want to consider discussing this approach with your doctor.

Gary Pepper, M.D

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How to Talk to Your Doctor About Thyroid Medication

Mary…you’ve made my day! I am glad you found my suggestion about “how to talk to your endocrinologist”, helpful. I am absolutely serious about approaching your physician in this way, since it makes them aware valid new information is available explaining why some people need t3 to recover from symptoms of hypothyroidism. This approach is much more likely to elicit a sympathetic response from a physician than quoting from a book by a non-physician or using the more general “I read it on the internet” statement.

Here is what Mary had to say to metabolism.com:

Dr Pepper, thank you so much for this article. I love the last part of where you give us the perfect phrases to say to our doctor. I have been suffering with hypothyroidism for 14 years now (10 years undiagnosed, 4 years insufficiently treated). Over these years I have come to know quite a bit about my condition and can speak with my doctor using the correct terminology most of the time, but not always (I have to get through the brain fog). Your phrases are just what I need to say to my doctor since I believe I have a conversion problem. I will enjoy presenting the study to him an talking to him about polymorphism and deiodinase! 🙂 Some people tell me I should have changes doctors along time ago. My doctor may have given up on me but I will not give up on him. I am determined to educate him. He did recently admit to me that he doesn’t know much about the thyroid. I fail to understand why the vast majority of General Practitioners don’t get up to speed on this subject since so many of their patients are suffering from thyroid problems. My doctor has wasted time and money giving me anti-depressants and appetite suppressants (Reductil) and sending me to a counsellor. Thanks again for helping.

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Wondering if t4 (Synthroid) Treatment of Hypothyroidism is the Answer

Prosanta asks metabolism.com if her thyroid blood test results indicate that treatment with t4 is required. I suspect that she is also wondering if other forms of treatment might be better (Armour Thyroid for example).

Here is what Prosanta writes:

Iamsuffering from Diabetes type2.recently on routine Blood test—
FT3(ECLIA) 2.33pg/ml
FT4 1.07ng/ml
TSH 9.32microIU/ml
AntiThyroid Peroxidase 37.02IU/ml
Do I need to take only Levothyroxine

In response to her question I offer my thoughts on whether someone beginning with thyroid hormone replacement therapy should start with t4.

Hi Prosanta

You know I can’t recommend medical therapy in this forum. I can make some general comments, however.

There is debate among endocrinologists about what level of TSH indicates a clinical degree of thyroid deficiency, but there is no doubt that a TSH of 9 is abnormally high. Since elevated TSH almost always indicates that the pituitary gland is releasing excessive TSH in response to thyroid hormone deficiency, unless there is a pituitary tumor (exceedingly rare), replacement therapy with thyroid hormone is indicated.

Thyroid hormone replacement therapy in the U.S. usually consists of taking a pure t4 product such as Synthroid or levothyroxine (generic t4). On this website you will notice extensive posting about treating hypothyroidism with alternative forms of thyroid hormone replacement, particularly desiccated thyroid products such as Armour Thyroid. An appropriate concern in a situation like yours is whether to take t4 only or to use desiccated thyroid or t4 plus t3 therapy.

If you are like most people in this country being treated with t4, you will wonder why someone might need alternative forms of thyroid hormone replacement. In the past year or so researchers have discovered that a portion of the population lacks the ability to normally metabolize t4 into the highly biologically active t3. This means that affected individuals may continue to experience symptoms of thyroid hormone deficiency when treated with conventional t4 therapy [http://www.metabolism.com/2009/11/07/breakthrough-discovery-thyroid-hormone-therapy-part-2/ ]. How does a person know if they won’t respond to t4? The simpliest approach is to try t4 and see how you feel. Then you and your doctor can decide whether you are a t4 responder or not.

You may be aware that Armour Thyroid and similar products are in very short supply in the U.S. Even if some advocates of desiccated thyroid therapy for hypothyroidism argue that only desiccated thyroid can result in a full return to normal, in my opinion the present shortage makes t4 therapy the clear initial choice. If symptoms of hypothyroidism persist even after a full course of t4 has been tried, then you may be forced to join the ranks of those struggling with the pharma industry to get desiccated thyroid products.

Please discuss these ideas with your own physician.

The disclaimer and terms of service of metabolism.com applies to this and all my posts on this website.

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Breakthrough Discovery in Thyroid Hormone Therapy: Part 2

Treatment of hypothyroidism (low thyroid function) is accomplished by administering thyroid hormone by mouth in sufficient amounts to restore levels back to normal. At first glance this might seem like a simple goal to achieve. The truth is hormone replacement therapy is complex because there exists two very different thyroid hormones and because levels of thyroid hormone in the blood do not always reflect the amount of thyroid hormone within the cells where the hormone exerts its effects. In Part One of this blog I began to discuss how genetic differences among individuals could explain why some people need a complex mix of thyroid hormones to adequately treat hypothyroidism. In Part 2, I want to explain the nature of the differences between individuals and how it determines what sort of thyroid hormone therapy may be needed.

In May 2009 a group of researchers (Panicker, V. et al) in the UK published the WATTS study, the largest and most comprehensive study to date, of hypothyroid patients treated with combination t4 and t3. The goal of the study was to discover whether genetic differences in the population of hypothyroid patients accounts for some individuals needing t3 in addition to traditional t4 therapy. The researchers looked at 697 hypothyroid individuals and analyzed their DNA for differences in the portions controlling crucial enzymes which process thyroid hormones known as deiodinases. These enzymes are found widely distributed in the body including the thyroid, brain, muscle, liver, kidney and pituitary gland. As explained above, deiodinases convert t4 to the much stronger form of thyroid hormone, t3. At the same time the researchers measured patients’ mood and sense of well being on t4 alone and when t3 was added to the therapy.

Key findings of the WATTS study are that there is a substantial difference among individuals in the genes that make the deiodinases. In other words, due to genetic differences (mutations), there are differences in the way individuals make t3 out of t4. In a group of people, mutations in the genes that make a particular protein (in this case, the deiodinase), are called polymorphisms. The researchers discovered that a certain mutation in the deiodinase gene is associated with a poor sense of well being on t4 only therapy, and in the presence of this mutation a significantly better response to adding t3 can be found compared to those without this mutation. Of the group of hypothyroid patients studied in the UK about 16% possessed the faulty deiodinase gene. In other groups in other countries the percentage of people with this mutation could be higher or lower.

The traditional treatment of hypothyroidism is to administer t4 (Synthroid, Levothyroxine, Levoxyl etc.). It is the conventional wisdom that inactive t4 is converted in the body to the active thyroid hormone t3 by “peripheral conversion” in sufficient amounts to restore normal thyroid balance. The recent breakthrough discoveries described in the WATTS study reveal for the first time that individuals differ in how their bodies process (metabolize) thyroid hormone. While some may convert enough t4 to t3 in the cells of the body to restore normal function, due to genetic differences some individuals will not be able to make enough t3 leaving them with persistent hypothyroid symptoms. Since the problem is a deficiency of t3 within the cells of the body, measuring thyroid hormone levels in the blood cannot adequately reveal the problem. T4 replacement treatment alone can result in thyroid levels that appear normal on blood tests so doctors conclude that persistent hypothyroid symptoms are not related to the hormone therapy.

Based on my personal experience and the documented experience of many of the members of Metabolism.com it is clear that endocrinologists and other physicians are often reluctant to consider combination therapy for hypothyroidism, either by using Armour thyroid or adding t3 (Cytomel, liothyronine) to t4 only therapy. With this new research in hand, hypothyroid individuals and their advocates can finally state with confidence that: Yes! There is a firm scientific foundation for combination t4/t3 therapy and; No! We are not just chronic complainers or kooks. If I had hypothyroidism and was going to request a change in my thyroid treatment I would say something like, “Due to polymorphism of the deiodinase gene I probably possess a defective D2 deiodinase and therefore my peripheral conversion of t4 to t3 is impaired. I need t3 added to t4 to compensate for reduced intracellular t3 levels which cannot be detected on blood tests. Without t3 I continue to suffer with cellular hypothyroidism which is the likely cause of my persistent symptoms.”

If you try this approach and your doctor looks bewildered hand them a copy of the study by Panicker et al in the Journal of Clinical Endocrinology and Metabolism, 2009, 94(5): 1623-1629.

Gary Pepper, M.D.

Editor-in-Chief, Metabolism.com

Notice: This article is for informational purposes only and does not substitute for the advice or treatment of your own physician. The disclaimer for all blogs at metabolism.com, applies.

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Armour Crisis Creates New Alliances

Good things can develop during a crisis situation. For me it was the eye opening experience I had this week by participating in The Thyroid Patient Community Call. The Thyroid Patient Community Call is a group internet telephone call hosted by Janie Bowthorpe, author of Stop The Thyroid Madness. During the 90 minute session I was able to interact with dozens of callers as well as Janie herself. Needless to say, Janie’s audience is mostly individuals who are deeply committed to maintaining Armour Thyroid as a treatment option and who are equally angry with the field of Endocrinology which backs the ban on dessicated thyroid hormone. I knew this audience wanted answers to some very tough and troubling questions. For a few days before the call I needed to review for myself just how this crisis developed, and how I became a lightning rod for the growing controversies. I believe this process was necessary and therapeutic.

Being a strong advocate of t4 plus t3 therapy and of Armour Thyroid, I was in sync with most of the topics being discussed on the call. What was hard for me was hearing the out pouring of stories describing how endocrinologists had alienated (infuriated) so many thyroid patients. How to explain but not excuse the inflexibility, wrong headedness and arrogance of a whole field of medicine on a topic central to its mission, my own field for the past 25 years? My head still hurts thinking about it. For those wanting to hear how this played out can visit Talkshoe.com which hosts these shows and follow the instructions for listening to past episodes of Janie’s show. Perhaps Janie can give more specific instructions by posting them here.

I came away from Janie’s session with a firm recognition that the field of Endocrinology is in serious need of a make-over. Imagine a Democrat walking into a room full of staunch Republicans and asking everyone to join him in a sensitivity training program. It is a lonely job.

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Eric Pritchard Brings Historical Perspective to “T4 Only” Treatment Bias

Eric Pritchard brings great insight showing how, for years, the field of endocrinology failed to acknowledge growing evidence of the inadequacy of “t4 only” therapy for hypothyroidism. Eric puts together the historical clues that should have paved the way for acceptance of t4 plus t3 therapy . We are now seeing almost irrefutable evidence ** (http://www.metabolism.com/2009/10/03/breakthrough-discover-t3-genetic/) ** that t4 by itself cannot in all cases provide enough active thyroid hormone to treat hypothyroidism. This is occurring at precisely the same time the practical solution to t4 plus t3 replacement therapy (dessicated thyroid hormone) is being chased from the shelves of pharmacies around the world.

Thanks Eric, for bringing your knowledge and insight to this crucial debate.

Eric writes to metabolism.com :

It is quite amazing that after 50 years of abusing some patients with the T4-only therapy, that medical is beginning to recognized that some patients do, in fact, require T3. It is about time for the practice of medicine to catch up with medical science. In 1960 Dr. Marshall Goldberg published a paper entitled “The Case for Euthyroid Hypometabolism,” which recommends a T3 therapy. About that same time researchers like Refetoff were noticing a resistance to T4. Refetoff, et al., discovered the cause, peripheral cellular hormone resistance in 1967. Subsequently, Braverman, et al., discovered peripheral conversion in 1970 and determined that 80% of all T3 comes from peripheral conversion. However, not to be swayed from the old thyroid-gland-is-directly-connected-to-symptoms paradigm, endocrinology has declared peripheral conversion to be fault free (really amazing) and simply ignores the potential for increased hormone reception. To support this wacky notion, they produced questionable studies that proved their old paradigm. These studies showed that the active hormone, T3, was ineffective and the inactive hormone, T4, was effective in spite of knowledge of the relative activity discovered by Gross and Pitt-Rivers in 1952.

All of this reminds us of medicine’s rejection of the empirical antispetic discoveries by Drs. Semmelweis and Lister. Why it was not minute particles of the cadavers that were being disected prior to surgery and child birth, it was the bad humors in the air. The post surgical infections and deaths could not upset the bad humors paradigm. Only after concerned heads of surgury demanded washing up before operating, the invention of the microscope, and Pastuer’s discovery of bacteria, did the merchants of death and illness realize reality.

Endocrinology laughed and dismissed Dr. Goldberg a half century ago, just as medicine drove Semmelweis to his death.

There are physicians who believe that medicine is an art. I have come to that conclusion as well, but not for the same reasons. I believe that medicine is an art because medicine does not have the discipline to be a real science. Real sciences react to counterexamples. We have seen counterexamples to the thyroid gland only diagnostics and T4-only therapy prescriptions. However, endocrinology and thyroidology have dismissed these suffering souls with diagnostic excuses such as “nonspecific symptoms” and “functional somatoform disorder” to blame medicine or blame the patient for the patients continuing suffering. Both of these diagnoses could be avoided if the differential diagnostic procedures had been followed — including all possible causes for the patient’s symptoms, euthyroid hypometabolism, deficient peripheral conversion, deficient peripheral cellular hormone reception. But in a perversion of the logic underlying differential diagnostics, medicine claims that the thyroid gland is first the only possible cause of the symptoms and second, when it fails, the symptoms have many causes — which were not tested.

Medicine is an art because it does not have the discipline to use clear language. In spite of demands for clarity of definition dating back to the 18th Century and undoubtedly earlier, and demands for clarity in medical guideline authorship protocols, “hypothyroidism” may be restricted to only the thyroid gland or may embrace the entire greater thyroid system. In either case, the diagnostics and the therapy recommendations are only applicable to the thyroid gland. Those who suffer from extra thyroid deficiencies in the greater thyroid system are simply allowed to suffer in spite of the existence of proven therapies.

Medicine is an art and not a science because it ignores counterexamples. There are patients who require T3 without any T4 as they will become thyrotoxic on the T4, but require the T3 to overcome hormone reception resistance.

There are patients who have had unsuccessful therapies with all synthetics but live well on desiccated thyroid. The laughter at the use of desiccated thyroid is a reminder that medicine does not have courage to recognize counterexamples and does not have the will to deal with them. Thus, endocrinology is really an art pretending to be a science as ignores suffering patients — perhaps a million in the UK and another 5 million in the US.

One could only wish that those laughing fools develop a thyroid related malady that endocrinology chooses not to recognize and then suffer the slings and arrows of mass medical malpractice that has been in vogue for the last half century.

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