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on combined T4/T3 therapy, or feeling better on thyroid meds

Posted Sep 17 2005 12:00am
Important Disclaimer: I am not a doctor. I am a thyroid cancer patient. None of what follows is intended to provide medical advice, only food for thought, and perhaps some useful information for other thyroid patients to bring to the attention of their own doctors.

Nearly all hypothyorid and thyroid cancer patients are treated with T4 hormone replacement alone, almost always the name-branded Synthroid, sometimes Levoxyl. There is, however, another hormone produced by the thyroid gland, T3; a synthetic version of T3 called Cytomel is readily available. Yet by far the vast majority of thyroid hormone replacement users have never been treated with T3. Why not? The subject comes up two or three times a month over on the Yahoo! Thyroid Cancer Support Group, and it usually goes something like this: My endo says my levels are fine, but I still feel crummy. Has anyone tried combined T4/T3 therapy?

Every time I see that reliably controversial topic raised, I get annoyed. Not at the poor innocent who has posted the question, but at the endocrinology industry that continues to screw around with hapless hypothyroids and thyroid cancer patients, year after year. So if you're searching for answers on combined T4/T3 therapy, you may find some here.

Endocrinologists avoid prescribing T3 as if it were pathological, completely ignoring the fact that normal functioning thyroids do indeed produce it. They usually cite three issues with T3, as follows:
1) it's not necessary, since all cells in the body can convert T4 into T3 as needed; 2) it's dangerous, since overdose can produce thyrotoxicosis, with symptoms including palpitations and high blood pressure; and
3) it's not as effective, since its half-life is so short (one day, as opposed to 7 days for synthetic T4.)

To these issues, I offer these common sense rebuttals:
1) If it weren't necessary at all, why would normal healthy thyroids make it in the first place? Also, the fact that people can survive without it is not dispositive of the supposition that they could do better with it. This is, at heart, a quality of life issue.
2) It is true that overdose can produce very serious problems, but these same problems can be caused by overdose of T4. Saying "it's too dangerous!" is just silly. If we were to follow that logic, no one would ever get thyroid hormone replacement treatment, and I'd be dead right now. Pharamacists hand over deadly medications to patients millions of times a day, and yet no one questions the practice -- because doctors write appropriate prescriptions for their patients. I really think endocrinologists should give themselves more credit.
3) Ah, the half-life issue. T3 is more rapidly metabolized, and so it is harder to get a nice, even supply of T3 into the bloodstream if the patient wishes to take a single dose once a day. The solution is, of course, time-released T3, which can be easily prepared by a compounding pharmacy. Some patients have no difficulty in splitting their T3 doses over the course of a day to maintain an even keel, so to speak. But some combined T4/T3 patients (like me) have no problems whatsoever taking all their meds at one time each day -- the T4, with its longer half-life, helps keep the overall level of thyroid hormone stable.

In spite of these counter-arguments, the established endocrinology community continues to spurn combined T4/T3 therapy. For an example of those holding the prevailing opinion, take Dr. Kenneth B. Ain, author of the generally superb and only somewhat condescending The Complete Thyroid Book. I "know" Dr. Ain from his frequent contributions to the above-mentioned online support group, and let me tell you: he has apparently infinite patience for repetitive questions but not much for stupidity, and he'll come right out and tell you if what you're talking about makes no sense whatsoever. I appreciate having a straight-shooting professional out there making sure the group doesn't wander too far afield, and I recognize that Dr. Ain's contributions to the group are invaluable. He has many years of thyroid and thyroid cancer treatment experience, and there's no one else in the group who comes close to having his level of authority because of it.

But along with that authority there often comes a kind of arrogance. And so it is with Dr. Ain, at least with respect to the combined T4/T3 question. Here we find him completely dismissing the possibility of combined therapy's use for thyroid cancer patients:
The only role of T3 for people with thyroid cancer is for the temporary preparation and recovery from hypothryodism for radioiodine treatment, thyroglobulin tests, and scans. (Complete Thyroid Book, p 152)
And here we find him repeating the Standard Line Against T3 as I described above:
The only small study suggesting T3 supplemention of levothyroxine therapy for hypothyroidism was flawed and could not be verified or replicated by several larger studies done thereafter. T3 can make you thyrotoxic, which can be dangerous, as we discuss in Chapter 4. Since all hypothyroid people on T4 will make T3 because of the laws of biology and biochemistry, adding T3 is not helpful and could be harmful. [...] [P]hysicians cannot ethically recommend a therapy that could be potentially harmful when there is no perceived benefit. (p. 244)
These two brief quotes more than adequately summarize Dr. Ain's feelings about the use of T3. There is no benefit to hypothyroid people in its use, he says, and in fact it could be harmful. Happily, there's a considerable amount of professional, medical disagreement with Dr. Ain's position, but it's all rather "below the surface" -- rarely published in the journals. Dr. John Lowe and the Dr. Richard Shames have both discussed their problems with the newer studies which refute the contention that adding T3 to a hypothyroid patient's therapy was beneficial. I'm not a doctor but I am extremely familiar with the kinds of study bias, bad design, and selective reporting of facts that Lowe and the Shames are describing here, and I still think that combined T4/T3 therapy is a good idea.

But what about Dr. Ain's assertion regarding all that research? I think that while Dr. Ain's opinon is supported by whatever research is out there, that doesn't mean that the research itself was properly or even honestly done -- that is, without a pre-set agenda to prove or a sponsor to please. Recent reports on the inaccuracy of scientific research would seem to support my position.

But what I really don't understand about Dr. Ain's opinion (which is, remember, exactly the same thing as the mainstream opinion) is that even he readily recognizes that:
The thyroid gland usually releases around 80 percent of its thyroid hormone as T4 and 20 percent as T3.(p 9)(emphasis added)
You would think that if the normally functioning gland produces not just T4, but T3 as well in a non-insignificant amount, that fact alone would argue for combined T4/T3 therapy -- but not so.

This issue eerily parallels the cheerful pronouncements of mid-20th century doctors who declared that evaporated milk and early baby formulas were just as good as mother's milk, and as a result, nursing became stygmatized as "low class" or "poor". Yet now as each year goes by, formulas are newly fortified with yet-another essential nutrient that has been identified in mother's milk. So, when is the medical establishment going to learn that natural human phsyiology should be the model on which treatment is based?

Combined T4/T3 may not be required for good health, but if a patient isn't feeling well on his current therapy, why not give it a try? Some people may fare better on straight T4 therapy, and if they feel well, there is no reason to change. But for the many hypothyroid or thyroid cancer patients who continue to feel less than optimal, combined therapy could help them feel better.

So what if you want to try it?
There are a number of practitioners who do "believe in" combined T4/T3 therapy, if only because they believe the evidence of their own eyes: patients who report to fewer symptoms and more well-being when on the therapy than not. In addition to the above-mentioned Drs. Lowe and Shames, one proponent of combined therapy is Dr. Larrian Gillespie, The Hormone Diva. In her book, You're Not Crazy, It's Your Hormones, Dr. Gillespie says:
Now, remember the body "naturally" produces a ratio of 90% T4 to 10% T3 by weight...(You're Not Crazy, p27)(emphasis added)
Dr. Gillespie says 10% by weight, whereas Dr. Ain says 20% of the hormones produced. Are they saying the same thing in different ways? I suspect so, because T4 is a larger molecule and so will take up a greater proportion of the whole by weight. Since Dr. Gillespie has had success in her practice using her dosage formula, you could use it as a starting point if you wish to bring this subject up with your own endocrinologist. You'll want approximately 10% of your total dosage to be delivered via T3, but since one microgram of T3 has the equivalent "strength" of 4 micrograms of T4, it's not as simple as splitting a 150mcg dose of T4 into 15 mcg of T3 and 135 mcg of T4! Dr. Gillespie offers this simpler formula for converting a straight T4 dosage into combined T4/T3 doses:
[D]ivide your T4 dose by 13. This will give you the amount of T3 for proper balance. Multiply the value by 9 for the [new] T4 level.(p. 29)
Sounds easy enough, right?

Now you'll just have to convince your endo to let you try it. You'll also have to pay more, because Cytomel is never a covered drug on medical insurance in my experience. But you just might feel better.

A bit on Thyroid Hormone Intolerance
When I was first diagnosed hypothyroid,I was put on a straight T4 therapy. I felt so horrible, I literally told my doctor, "I don't want to live this way." It is true that there is no such thing as "thyroid hormone intolerance." You can't be intolerant to thyroid hormones, we all need them to live. But what can happen is a kind of systemic attack (for lack of a better word) if you have an underlying condition that leads to problems when you start supplementing with thyroid hormones. Symptoms include: insomnia, headaches up to and including migraines, palpitations, and muscle and joint aches. Two conditions that can cause these symptoms when thyroid hormone supplementation is introduced are anemia and adrenal fatigue. The T4 prescribing information warns about these two conditions, but doctors never test before writing out the scrips. Seriously, they don't, so you'll have to look out for yourself.

On the anemia, it's iron stores that are most important here; Dr. Gillespie advises targetting serum ferritin around 100.

Unfortunately, most endos brush off the idea of adrenal fatigue-- if you don't have Addison's Disease or Cushings Syndrome, those adrenals must be fine! Why is there no middle ground with these docs? They'll readily treat a thyroid that's only limping along at half-capacity, or give progesterone or testosterone when those are testing out low. There's just huge skepticism over the idea that adrenal function could be sorta-OK, but not exactly right. So adrenal fatigue can be hard to diagnose, and it's controversial to treat, too. But unless your adrenals are OK, thyroid hormones are going to make you feel horrible. Check out the "adrenal fatigue" link above if those symptoms sound familiar.

So you can see there a number of reasons you can feel crummy while on thyroid hormone replacement. Look into these two conditions first, and once you know you're OK, if you're still not feeling your best, give the combined T4/T3 therapy a try.

Additional Resources
Mary Shomon's indispensible site, Thyroid Disease on the About.com network.

Mary's book, Living Well with Hypothyroidism

Richard L. Shames and Karilee Halo Shames, Thryoid Power Ten Steps to Total Health

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