Updated 2/2018

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Introduction: why should you care about thyroid?

Here are two reasons to care about thyroid:

1. There is a clear connection between the process of thyroid hormone regulation and bipolar disorder. The problem is, this connection is only just now beginning to become evident, and how the connection works is basically a mystery. Two studies recently showed a strikingly high rate of autoimmune-caused thyroid problems in people with bipolar disorder, far more than you would expect to find. Vonk , Kupka Thyroid problems are more common in the complex forms of bipolar disorder (mixed states and rapid cycling) than in classic bipolar manic patients.Chang Signs of thyroid auto-immunity are much more common in people with anxiety and depression, particularly the forms of anxiety which don’t easily fit into typical “anxiety disorder” labels.Carta

2. Two studies have shown that people with bipolar depression were less likely to get better if they had low thyroid levels, whereas the ones with higher levels responded pretty well.Cole, Frye The same phenomenon was recently shown in “unipolar” depression.Gitlin,Abulseoud These four studies are the basis for a treatment approach you could consider, particularly if depression is your main problem: gently pushing your thyroid status toward the “hyperthyroid” end of normal, if you happen now to be toward the hypothyroid end of normal. This idea is logical but surprisingly untested. There is only a preliminary test with no control group.Lojko

But another research team recently concluded that reduction in thyroid function can exacerbate bipolar symptoms even in euthyroid subjects.” Frye In other words, people who are in the normal range (“euthyroid”) can see their bipolar symptoms getting worse if their thyroid levels get low, even if that reduction leaves them still in the normal range.

Most doctors will not raise this option of adding thyroid unless you are clearly already low. It certainly isn’t the first thing to try for depression. But if you have tried several approaches and are considering what to do next; and if you have enough “bipolarity” to make antidepressants a concern, then it might be worth considering this approach.

Here’s the logic: as long as you and your doctor are careful, and don’t bump you up into hyperthyroidism, there is almost no risk in trying this approach. It does require a series of blood tests, which a lot of people hate. And there might be some risk if you end up hyperthyroid.

UPDATE 2018: even though the above data have been around for 10 years, frankly, almost no doctors or NPs will do this. But now there’s basically a complete How-To manual, complete with in-depth references and a complete consideration of possible risks (which may be few, and even if present, may be far less than alternative treatments). When you’re ready for the details, and ready to try to explain all this to your provider, get this book — The Art and Science of Thyroid Supplementation for the Treatment of Bipolar Depression — and read it and you will be ready to explain it to your provider. If you can get her to read Chapter 2, the Quick Guide, you’ll have done well.

Not ready for that step yet? Read on. First a summary, then more details.

You need to know about thyroid and bipolar disorder for several reasons:

1. There is some relationship between the two, though poorly understood. 2. You need to make sure your thyroid is okay before you begin treatment for bipolar disorder, because if it’s not okay, you might not respond fully to treatment; and

it’s usually pretty easy to get your thyroid hormone in the right place, which by itself could help your symptoms somewhat. 3. Thyroid hormone is sometimes used as a treatment for bipolar disorder, even if your thyroid is “normal” (by lab tests, anyway). 4. And finally, lithium commonly interferes with the thyroid system, so you’ll need to understand a bit about thyroid if you’re going to take lithium.

Below are some basics about thyroid hormone, then some information about using it as a treatment.

What is thyroid hormone?

Thyroid hormone is made from an amino acid (which are the building blocks of proteins; in this case, it’s the amino acid “tyrosine”). Here is a picture for you chemistry types:

Your thyroid gland attaches 4 iodine atoms — the I‘s around the structure above — to the amino acid. This form, called T4 for short, is the molecule many patients take for thyroid hormone replacement when they can’t make their own. It comes as a pill. You might recognize the names: levothyroid, Levoxyl, Synthroid. Most of the hormone your gland makes comes out in this T4 form.

The other form you need to know about is T3. You can see in the picture above that the difference is just one less iodine atom. Cells in the brain, liver and some other organs take T4 from the bloodstream and convert it to T3 by removing one of the iodine atoms. T3 is the “active” version of the hormone. About one fifth of the hormone produced by your thyroid gland comes out as T3.

[Update 4/2008; revised 3/2014: Use of T3 as an antidepressant

is getting a lot more attention lately and generally the studies are strongly supportive of this approach. But that’s for “unipolar” depression (Major Depression), not bipolar depression. T3 might work for bipolar depression also — indeed, I’m pretty sure it does, quite well, rather often, in the short run. A friend of mine wrote a remarkable paper showing this.Kelly

However, we have less information to determine whether using T3 might be destabilizing in bipolar depression, as conventional antidepressants can be. I’ve had a couple patients who responded well initially then seemed to have “rapid cycling” which resolved when I switched them from T3 to T4. My opinion: until we have a better impression on this longer-term issue, T3 should be used with caution in bipolar depression. It’s a good idea as an add-on to an antidepressant in unipolar depression — but in bipolar depression, I currently use T4, not T3. Of note, in a unipolar depression study, T3 worked better for patients with low, not high TSH.Sokolov

What does thyroid hormone do?

Here’s the official medical school version, then a translation to plain English:

regulates nuclear transcription of genes responsible for protein synthesis;

increases cellular metabolism, growth rates;

facilitates mental processes [that’s a good one, eh?];

increases in endocrine gland activity;

stimulates carbohydrateand fat metabolism;

decreases cholesterol, phospholipids, and triglycerides;

increases fatty acids;

decreases body weight;

increases heart rate, respiration, muscle action.

Translation: roughly speaking, it sets your idle”, rather like a car mechanic sets the idle of your car by adjusting the carburetor. If your thyroid level is set too high, you burn a lot of energy even sitting still. People feel agitated, buzzy”, and have tremor in their hands.

If thyroid hormone is too low (“hypothyroid”), you don’t burn much energy except when active. It’s as if your “carburetor” is set to idle too low: when you stop doing something, you practically turn off completely.

What does thyroid hormone do for your head?

That was rather the point of this all this, wasn’t it. Sorry to take so long getting here. We know that if your thyroid hormones are low, you can get depressed. We know that if your thyroid hormones are too high, you can get anxious. Beyond that things get pretty murky. For a little more on this, although its pretty technical, click here.

But of course the other point of all this was that thyroid hormone can be used as a treatment for bipolar disorder. Even though we don’t know yet how it works, or how often it works, we know it definitely does works for some people (for a summary of the medical literature showing it does indeed work, click here).

How is thyroid measured?

The standard measure of thyroid function is “TSH”: Thyroid Stimulating Hormone. TSH is the signal from your pituitary gland, up there in the middle of your brain just under your hypothalamus, that tells your thyroid gland to “MAKE MORE” thyroid hormones. When your gland makes too little hormone, TSH goes up. It’s yelling: I said, make more thyroid hormone!” So a high TSH goes with hypothyroidism, meaning too little thyroid hormone.

And, you guessed it, a low TSH happens when your brain is seeing a lot of thyroid hormone. It no longer has to yell, it’s whispering now: ok, ok, that’s plenty already”. And if your thyroid levels were really high, the TSH would go down so low we might not even be able to find it with a lab test.

Ok? Well how low a TSH can you get and still be okay? (Remember, becoming hyperthyroid means increasing your risk of osteoporosis, as discussed in detail here). That is, how far can you push your thyroid dose up, before the TSH would go so low you would be “hyperthyroid” and therefore taking risk with your bones? Answer: nobody knows for sure. One research group has shown people who were maintained “hyperthyroid” didn’t get bone density decreases we usually would have expected, over a period of 5 years.Ricken They didn’t have any heart problems eitherGyulai, which you may remember is the other known risk of hyperthyroidism. But what about 10 years from now? We don’t know if it’s okay to be hyperthyroid that long.

[Update 3/2014: the upper limit of “normal” in most labs, for TSH, is over 4 (don’t worry about the units, just watch the number). But a recent re-analysis of “normal” suggested that the upper limit might be better considered anything over 2.5Davis (full text link at bottom of abstract) . The National Academy of Clinical Biochemists also suggested 2.5 as an upper limit of normal (as cited in this review by the American Association of Clinical Endocrinology; pg. 999, last full paragraph).

From here, things get a little more complicated. Remember the simple version you’ve learned so far: if you could take thyroid hormone and get good symptom control, without symptoms of hyperthyroidism, you might get benefits without risks.

Thyroid hormone as a treatment for bipolar disorder

Thyroid hormones can act as a mood treatment, even when a person’s thyroid levels seem to be “normal”. Read that again, it’s really important.

Okay, so does that mean their thyroid levels weren’t really “normal”? This is probably true some of the time. But in some people, it looks like the hormones, given on top of the person’s usual production, change something in the brain that changes mood. In at least some cases thyroid hormones are a treatment for mood problems that aren’t thyroid problems in the first place.

Instead, in some cases, these hormones act just like lithium and valproate and other “mood stabilizers“. They help stop mood cycling — particularly, it seems, in people who have “rapid cycling”. This approach is generally used after a person has tried several of the well-known mood stabilizers, because there is only a little research about thyroid treatment to go on at this point (in part because there is no manufacturer in a position to make big money from the research, for one reason. Thyroid hormone has been around in several forms for more than 40 years).

Usually the form that is used as a mood stabilizer is T4. By contrast, T3 is usually used as an “add-on” to antidepressants, because some research has shown it can boost the antidepressant’s effects. One of the reasons to look closely at thyroid’s potential as a treatment is because the risks of this approach, properly managed, can be extremely low. Therefore, even if the potential benefit is not very clear (who responds? how often? how much hormone? which form?), it may still be worth considering when compared to other medication alternatives with more clearly demonstrated benefits, but higher risks as well.

What are the risks?

[UPDATE 2018: These are reviewed in great detail in Dr. Kelly’s Art and Science of Thyroid Supplementation for the Treatment of Bipolar Depression. As soon as you’re serious about understanding all this, get that book, you’ll need it. What follows below is just an introduction to the issues. Dr. Kelly has reviewed the available data more thoroughly than anyone.]

Obviously, we want as much symptom control as we can get without side effects or medical risk. The problem is, too much thyroid hormone can make you hyperthyroid” , the same condition people get when their own thyroid hormone production increases out of control (a list of symptoms follows below). We know from their experience — people who are hyperthyroid on their own — that being hyperthyroid has two significant risks. Whether these risks actually apply to people who take thyroid hormone but who do not have hyperthyroid symptoms, is not clear, because these theoretical risks have not been observed but the number of people studied remains small.

Risk #1, Cardiac: People who are “hyperthyroid” from their own thyroid gland, even for a short while, can have a temporary rhythm problem in their heart called atrial fibrillation. Here are some basics about atrial fibrillation, the main risk of which is having a stroke (clots form in the quivering atrial chamber then break off and head north, getting stuck in the narrowing brain artery system). In people over 60, having too much thyroid replacement tripled the risk of this atrial fibrillation. However, a review on this treatment approach concluded “on balance, the risks of properly monitored thyroxine treatment are almost non-existent”.Weetman

So far there are no reported cases of atrial fibrillation even using a high-dose thyroid approach but the number of research patients is still very small. Atrial fibrillation is not trivial. If you didn’t figure out you had it within three days, you could develop a blood clot in your atrium and flick off pieces into your arteries, causing a stroke or loss of a finger or toe — disastrous. So you’d better know what atrial fibrillation feels like if you’re going to try this approach. Make sure you and your doctor have agreed on what to watch for (I’m not giving you that list here because you should not even think about trying this without working closely with a doctor who agrees with the plan…)

Your heart rate can go much faster if you become hyperthyroid. That’s scary: two of my patients have gone to the emergency room because of it.(they did not follow my written instructions to lower the dose or call me if this kind of thing was starting to happen, but nevertheless, they had a frightening experience, not good). For a young healthy heart, a high rate is not a risk. Theoretically, one could take a heart that is already right on the edge because of underlying heart disease and tip it into trouble by accelerating its rate. This is not routinely described as a risk of hyperthyroidism but makes sense to me so I factor it in when I’m thinking about using this approach.

Risk #2, Bone: This only applies if you stay on high doses of thyroid treatment, presumably because you and your doctor have decided that the treatment is working really well. If you try the treatment and conclude in a month or two that it is not working, this risk is not an issue. The risk that has been associated with staying hyperthyroid due to an overactive thyroid gland is osteoporosis — loss of calcium in your bones, with a risk of fractures, especially when you get older.

But so far, in a 5-year follow-up of patients being treated with high doses of thyroid hormone for bipolar disorder, this was not a problem. Bone density decreased, because the average age in this study was 50, and we all are going down at that age (so to speak; it’s the voice of experience…). But there was no more bone loss than was seen in people of the same age and gender who were not being treated.Ricken

(Here finally is one place where being a heavy woman is an advantage: you’re much less likely to have a problem with osteoporosis. But if you’re fairly thin, or smoke, or your mother already has osteoporosis, you can’t afford to add another factor that could cause bone thinning. Here’s a little more on this topic for such women.)

Conclusions about risk: You can try this approach and face only theoretical cardiac risk which has not occurred in the research trials but which can be disastrous if not detected. Tricky, isn’t it? A theoretical risk: not clear if it applies at all but scary. On the other hand, when you know what to watch for, atrial fibrillation would be very hard to miss so if you got it you could go straight for help and you’d not face much risk to your heart, as long as you’re not likely to have underlying heart disease.

Symptoms of hyperthyroidism

This description of treatment with thyroid hormone presumes that you find a dose of thyroid that gives you good symptom control without symptoms of hyperthyroidism, which include

feeling hot when others are comfortable or even cold

sweating

thumping heart beats (“palpitations”)

weight loss (sometimes); eating more than usual

anxiety and nervousness

frequent bowel movements

decreased flow with your menstrual periods, or no period at all High dose thyroid

Several researchers are studying high doses of thyroid as a mood stabilizer approach, especially for rapid cycling. They use doses far higher than usual physical production, thus this is referred to as “supraphysiologic” or “hypermetabolic” thyroid hormone treatment.

The typical thyroid hormone replacement dose for people who are “hypothyroid”, is 100-150 mcg. In the high-dose approach, between 250 and 400 mcg may be used. Why doesn’t this just cause people to become “hyperthyroid”? That is a very good question. The answer is not known.

If you and your psychiatrist are going to consider this approach, you’ll need references for the relevant research. For a summary and an important reference paper, please see my page on High-Dose Thyroid for Bipolar Disorder.

T3/T4 Combination Treatment

Updated 12/2014

Debate continues as to whether to use T3 or T4 for mood purposes. I’m still uncertain. I’ve gone both ways. All three ways, in fact: the one, the other, and the combination of the two.

Each of one these approaches has their champions. You’ll find people speaking loudly in favor of T3. And T3/T4 combination. The softest voices are those of the groups that have been using T4 for decades and have the most published data on this issue.

For now, I’ve settled on using T4 when I want an antidepressant effect but also a mood stabilizing effect. This is based largely on the high-dose studies from the now-far-flung UCLA group of Whybrow and Bauer. They have been doing this for a long time.

Then there’s T3 alone. That approach has much more strength now that T3 was as good as lithium, with fewer side effects, in the big national STAR*D trial.Nierenberg

Finally, what about the combination of T3 and T4? You’ll find vocal advocates there too. I gathered the data on this about 10 years ago when the debate was really hot, but it did not clearly answer the question of what form to use. However, I’m not convinced that switching from T4 to T3/T4 is a key for anyone. I had one patient once where that seemed so but have not encountered any more in over 10 years. But maybe that’s because I’ve not been trying it in such a gung ho fashion. That’s the problem with individual clinical experience: you can easily confirm your own hunches. For a while at least.

Here’s my simplified strategy for now (entering 2015): if bipolarity is low, it’s mostly just depression, T3 is fine and simpler. But in folks with significant bipolarity I worry that it may be too much like an antidepressant and be destabilizing. That’s based on two cases, to be frank. My friend Dr. Tam Kelly has done this in well over a hundred patients , and published the resultsKelly, and he’s not worried. That definitely ought to mean something.

Nevertheless, based on the even more extensive experience of he UCLA group, if bipolarity is prominent, I use T4 for an antidepressant and mood stabilizing effect. In younger healthy folks I actively consider the high-dose thyroid approach.

When I’m switching back and forth I use this old table of conversion data.

Thyrolar T4 / T3 content Thyrolar-1 50 mcg / 12.5 mcg Thyrolar- 1/2 25 mcg / 7.25 mcg Armour Thyroid T4/T3 content Rees-Jones 60 mg, 1 “grain” 60 mcg/ 10 mcg 30 mg, 1/2 “grain” 30 mcg/ 5 mcg

If you’re ready for a pretty technical version and would like to see similar ideas from another doc’ (which would be smart), here’s another comment on this thyroid/bipolar relationship from Dr. Peter Brigham. Also take the link on his page to the old discussion of T3 and T4. We’re not much farther along than this expression of expert opinion, despite the pioneering and determined work of my colleague Dr. Tam Kelly.e.g.Kelly.bone