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.
Dear Dr. Pepper,
I read your post with interest and hope that you might be able to provide me with added advice.
I was diagnosed with hypothyroidism in 1990 and at that point began taking a relatively low dose of synthroid. Later, in 1997, I was diagnosed with fibromyalgia. I mention the latter only because a recent physician that I have been seeing told me that for people with both ailments, cytomel is better than synthroid.
I am now taking 50 mcg. of cytomel daily, after taking synthroid for 19 years, having worked up to a daily dose of .175 mg. The problem is that previous to developing hypothyroidism, I was slim and had a good amount of energy. Since then, however, I have had a considerable weight problem and suffer from severe fatigue on a daily basis — whether I am taking synthroid or cytomel.
Additionally, based on my last blood work, both my T3 and T4 are in the average range — neither too little or too much.
Do you have any ideas about the above. I would greatly appreciate any advice you can share.
Many thanks,
Nancy
Hi Nancy
Your story is not that uncommon. Many of the members here at metabolism.com share similar experiences.
As you know I cannot offer medical advice in this blog. But I can share some educational thoughts with you.
As I understand it, you are on 50 mcg of Cytomel daily and off Synthroid. Cytomel is relatively short acting and needs to be divided into two if not more doses daily, for best results. Personally I have had better results with combination t4 (eg Synthroid) plus Cytomel as the Synthroid supplies a background of thyroid hormone while the Cytomel supplies the “booster” effect.
If it weren’t for the Armour crisis, I would usually advise people in your situation to try dessicated thyroid since of all the choices it has offered the best clinical response at the best price. If you are interested you might ask you doctor if Armour or similar is a possible choice for you, then you will have to join everyone else in the struggle to obtain it.
Good luck and keep us posted.
Gary Pepper, M.D. , editor-in-chief, Metabolism.com
Dr. Pepper,
I read your blog with interest. When I was 18 I was diagnosed with hypothryoidism, due to change in insurance I had to switch doctors and subsequently (more than 20 years) tested normal instead of hypothyroid until 2 years ago. I went to a physician who ran a free t3, free t4, etc test and my t3 was at 307. He encouraged me to take RAI which I did as he said that my thyroid would end up burning out and I would be sicker than I was at the time. Since that time I have struggled to get within the normal range of 200-250 for t3. I am currently taking Synthroid @ 200 mcg. Given the fact that I do not have a thyroid, is it reasonable that the combination of t3 and t4 may work better than just the Synthroid alone? Is it possible that the fact that I don’t have a thyroid may be affecting the gene you spoke about? Or is that only for individuals who still have a thyroid?
Hi Angel
You may have noticed a few articles at metabolism.com describing how many people with hypothyroidism taking replacement therapy feel best when receiving extra amounts of t3, either as combination Cytomel and levothyroxine (Synthroid, Levoxyl etc), or in the natural product dessicated thyroid (Armour etc).
We are all born with a certain set of genes which determine everything about our physical selves. Our genes are constant throughout our lives. You may have the genetic makeup which requires t3 replacement but only by doing a genetic analysis would you be able to know that. An easier way is to ask your doctor if it is reasonable to try adding t3 to your Synthroid. Reducing your Synthroid dose may be necessary to accommodate the addition of the t3. After that you can see if the combination is better than Synthroid alone. Due to the acute shortage of Armour it is hard to recommend trying that, as you see on metabolism.com all the turmoil people are going through to get it.
As you know, only you and your doctor can decide what is appropriate therapy for you. My comments are for educational purposes only.
Keep us posted and good luck.
Dr. Pepper,
Hi, I am a mother of two, my oldest daughter Peyton(3yrs) , was put on synthroid 75, the bloodwork they take from the hospital when she was born came back high, so we took her back a week later for more bloodwork, it came back good, and over the years her bloodwork has came back good. But now, my daughter Dana’s(23 days old) bloodwork from the hospital came back high, so she’s on the synthroid now. they’re doctor wants to take Peyton off and test her to see if she can be taken off, if so, she thinks Dana does not need it either. They’re doctor said something, like I have something that is blocking their thyroid, because it’s just their first bloodwork that comes back high. Can I just have your point of view?
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
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 amost 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.
Let us know how you do.
The disclaimer and terms of service of metabolism.com applies to all my posts on this website.
I have a Hyper Thyroid and am tatally confused on the weight gain, what can I do or take for the weight gain?
Lynda
Hi Dr. Pepper,
Great article and so true! I am a testiment to augmenting T4 with T3. However I have a question. I think I remember you telling me once that T4 can block T3 absorption and/or efficacy. Am I remembering that correctly? And if so, to what degree?
I’m still constantly tweaking my Armour and Cytomel ratio for the best balance and often wonder if I should ease up on the Armour and instead take more Cytomel to more effectively address my low T3 count. What do you think?
Thanks and thanks for being my doctor!!!
Kimberly Bain
Hey Kim
I think I was trying to convey the idea that in order to achieve higher t3 levels by increasing t3 doses, sometimes we need to reduce sources of t4 such as levothyroxine and even Armour (which contains both t4 and t3). I agree with your idea that if you want to see how you feel by upping your t3 levels by increasing your Cytomel I would advise reducing the Armour dose. Please let me know if you need further instruction or how the change works out for you.
Best,
Dr. P.