Sunday, February 12, 2012

The Treatment of Depression with T3

Psychiatry is one of the few specialties where we are "allowed" to use T3 (the active thyroid hormone, instead of the safer prohormone T4) for treatment of resistant depression.  (Please see yesterday's post for a thyroid primer).  The literature for its use is extensive but old.  Much of it was done before there were very reliable lab tests for thryoid function, so symptoms such as pulse, insomnia, anxiety, palpitations and reflexes were measured to judge whether someone was made "hyperthyroid" with the treatment or not.  I suppose that made them bolder, back in the day (also, there were very few options, medication-speaking, so all the people studying resistant depression did a little study on T3.  For the same reason there is a ton of data on lithium for bipolar disorder. It was the only game in town for decades.)

In any event, I thought I would take the opportunity to catch up on the latest and greatest in T3 supplementation and safety issues, particularly since the very large STAR-D trial used T3 and found it equally efficacious in resistant depression to lithium use, and better than many other pharmaceutical tinctures.  Fortunately there is an up to date review from the Green Journal, T3 Augmentation in Major Depressive Disorder:  Safety Considerations.  The article had a number of interesting points, particularly with regards to the standard endocrinology method of treating hypothyroidism with T4 monotherapy.  I'll get to that in a bit.

All right.  So the weakness of most of the studies is that they were short, typically 2-12 weeks.  Also, most of them were studies of augmentation or acceleration with the old-fashioned antidepressants, the tricyclics (or TCAs).  And when I think of the tricyclics, I think of a cruder but much more medication-stringent time.  TCAs have lots of side effects (weight gain, dry mouth, fast heartbeat) and are fatal in overdose.  However, they are effective for many,  and folks with very serious depression where they were nonfunctional and suicidal who responded to the medicine would take them because being without proved worse than the side effects of being on them.  The SSRIs, with fewer (but still not insignificant) side effects had not yet been invented, and mildly depressed women were still being given B12 shots by their primary care doctors, who also advised them to smoke to give them energy and motivation.  (Or gave them a tiny bit of dexedrine in the morning and some barbituates at night.)

So we are dealing with a subset of very depressed people who do not respond to the tricyclics.  They don't seem to be hypothyroid by physical symptoms or the lab tests of the time, but a certain percentage would respond to augmentation with active thyroid hormone.  In addition, "accelerating" the tricyclics (which, like most antidepressants, take several weeks to kick in) with a dose of T3 up front (isolated to 2-4 weeks, then discontinued) seemed to work too.  There are fewer studies of augmentation with SSRIs, but these are also short and the results are less definitive.

Why would T3 help? What does T3 do in the central nervous system? Well, a lot.  The thyroid has fingers in almost every physiological pie, after all.  And T3 not only may act as a direct neurotransmitter, but it also seems to increase the efficiency of serotonin signaling, much like a modern SSRI.  T3 also enhances neurogenesis in the central nervous system and could also enhance noradrenergic signaling.  The conversion from T4 to T3 occurs all over the body, but in the central nervous system it uses different active genes than in the periphery and occurs within the cells.  These differences could explain my own clinical observations--that T3 augmentation seems to work best in folks already diagnosed hypothyroid that are on T4 monotherapy.  And the literature (such as it is) seems to support my observation (1).

(I am ignoring selenium and iodine deficiency for the moment as does this literature.  Much of North America has fairly selenium-rich soil except some of the Eastern Coastal plain.  Given the wide geographic distribution of vegetables and other produce, frank selenium deficiency is rare.  Also, with the advent of iodized salt, frank iodine deficiency is also rare so that babies are very rarely born with congenital hypothyroidism.  These facts do not mean that our selenium and iodine levels are optimized, but, again, I would say a frank deficiency is rare).

So the good news is that T3 augmentation seems to help some and (relying on some limited longer-term data up to several years) it seems to be relatively safe (particularly in the short term), though post-menopausal women need to watch the possible side effect of osteoporosis, and there is a continued risk of heart arrhythmia.  So in heart-healthy and strong-boned folks with a serious bout of depression, a small dose of T3 is a good option, even if they are clinically and by laboratory measure euthyroid (normal thyroid) particularly if they are the type to have serious episodes and then bounce back, rather than the more chronically low-grade depressed people.

The goal for longer-term treatment is to use a dose that keeps TSH at the low end of normal (or even somewhat below normal if there are no hyperthyroid symptoms) and free T3 at the high end of normal (I can tell you that the recommended dose of 25-50mcg almost always seems to overshoot this goal, but it probably reflects the long history of shorter-term studies), while monitoring bone density and cardiac side effects frequently, particularly in post-menopausal women.   T3 augmentation does seem to work better in folks with higher TSH and lower free T3s at baseline, suggesting we are, indeed, treating a type of "subclinical hypothyroidism" with depression symptoms, maybe those who convert T4 to T3 just fine in the periphery but who are poor converters in the central nervous system.  Again, this would support my clinical observation of long term treatment.  Fairly useless in the euthyroid except for temporary severe exacerbations, but useful in the hypothyroid or subclinical hypothyroid.

And what about those endocrinologists who are so very down on combination therapy with T3 and T4 for hypothyroidism?  I've had some tell me point blank (over the phone) there is no literature support for treatment of hypothyroidism with anything but T4 monotherapy.  I've had to pull out the "psychiatric indication" card and then they will back off, mostly because most folks in medicine are a little scared of psychiatrists and psychiatric patients.  There's a little bit of literature of psychiatrists as the last shamans of Western medicine.  We don't typically wear the white coats.  We treat the unexplained.  We exist apart.  We may well be witch doctors.  In the US, insurance payments regard "mental health" and "medical" as separate entities.  But I'm wandering a bit.

Well, what about that literature for combination therapy (T3 and T4) vs monotherapy (T4 alone) for hypothyroidism?  Multiple studies and a meta-analysis have proven no benefit for combination therapy over T4 alone.  However, in several studies, patients had a preference for combination therapy that could not be explained by lab results or quality of life measurements.  In Denmark, one study using double-blind crossover methods treated patients with T3/T4 or T4 alone to equivalent TSH levels.  49% of the patients preferred combination therapy compared to 15% who preferred T4 monotherapy, and quality of life measures and depression and anxiety ratings were generally better on combination therapy than on T4 alone.  T4 monotherapy is safer, less likely to result in hyperthyroidism.  But to say there is no support for the alternative is incorrect.

From the evolutionary point of view in general a bit of seaweed and some selenium won't hurt.  In the case of Hashimoto's one must take care with iodine supplementation lest one worsen the condition (this seems less likely to happen if selenium is topped off).  Selenium excess is also a pretty bad idea.

But looking at the more modern basis of hypothyroid and depression treatment, the science behind T4 monotherapy is not yet ironclad.  T3 might yet come back from its banishment to psychiatry.


  1. Nice post and I agree with your clinical observations as well. I can not get an endocrinologist to get off the T4 alone band wagon.

  2. "In addition, "accelerating" the tricyclics (which, like most antidepressants, take several weeks to kick in) with a dose of T3 up front (isolated to 2-4 weeks, then discontinued) seemed to work too."

    Coupled with the suggestion to use t3 to get levels up to the upper parameter of "normal", it seems that when we're depressed we might, possibly, be down regulating our t3 production. So if depression causes this response, just like an bacterial infection for instance, is there a possibility that increasing levels back to normal is counter productive? I mean for bacterial infections, if we [artificially] increase t3 again that would just increase glucose utilization and probably help the bacteria, mean whilst making us feel better (in the short term, at least?). A question I had was whether TCA's and SSRI's alike had any effect on free t3 levels.

  3. "Multiple studies and a meta-analysis have proven no benefit for combination therapy over T4 alone."

    Of course those studies can only shed light on the particular T3+T4 protocol they tested, which as I've noted before, is grossly mid-dosed based on the experience of my endo, who has probably followed more people on T3/T4 therapy than anyone else.

    Back in 2004, he had a letter in the The Journal of Clinical Endocrinology & Metabolism commenting on two of those studies:

    Note that since then he has found that even lower T3/T4 dose ratios generally work best long term (~1.2%).

    As the rebuttal letters indicate, the academic endos reject all this experience as quaintly anecdotal and call for huge studies to prove it—studies that of course only they could get funding to do. And they won't do it.

    I am only a humble happy anecdote, but I'd again suggest that all interested in this topic check out his new book when it appears:

    ...or his earlier one if you can't wait, though his methods have since evolved a bit.

  4. psychic24 - I meant to make more of a point during the article about how I don't particularly care to use T3 in euthyroid folks who aren't already on T4 for this very reason. Maybe there's something the body is doing we don't understand that we would interfere with by giving T3. I also think it is fairy useless chronically (again, except when the thyroid is already down for the count) because the thyroid will just re-regulate itself and produce less hormone to make up for the extra you are giving someone.

    William - I find it shocking that the previous studies did not control for TSH. I mean, seriously! What can you learn if the goal isn't a similar TSH for everyone and then compare the symptoms reaching that point with T4 alone or T3/T4? The authors of the Denmark study did exactly that, and they have some interesting speculation about the appropriate ratio of T3/T4. I linked the full text which is freely available from Pubmed. I'm glad you found an endo who has an open mind. It's almost like telling a cardiologist that butter is fine.

  5. "I find it shocking..."

    You may be amused at my endo's characterization of so many elite studies—triple blind: not only are the patients and investigators blind to the treatment, but the latter are also blind to the phenomenon they're studying!

    "I'm glad you found an endo who has an open mind. It's almost like telling a cardiologist that butter is fine."

    You may also be amused at another thing he never tires of saying: "The only people who are 100 percent sure about anything in medicine are medical students, malpractice lawyers, and well-compensated expert witnesses." I guess he's too polite to include academic endos, cardiologists, etc. :-)

    BTW, I'm pretty sure he'd share your reluctance to use T3 with people who aren't hypothyroid. I believe he regards what he does as simply bioidentical hormone replacement for those whose need it, not gung ho pharmaceutical intervention. Many hypothyroids don't get so labeled, however, due to the holy TSH doctrine he criticizes very harshly. So as I've said he often offers a trial of T4 for those with consistent symptoms and signs to see if they really do need replacement despite TSH that happens to fall within the very broad "normal" range.

  6. "It's almost like telling a cardiologist that butter is fine."

    Great final line, it made me laugh. Thanks.

  7. (Slightly OT, to continue what I said about my personal experience with going Paleo a year ago in another thread)

    Just for your information, about my n-1, which may be mediated by other factors than nutrition and was tainted by at least one mistake I made.

    (And I am explicitly NOT asking for advice).

    I have new doctor and he made some tests.
    My cholesterol went from 212 (october 2010, before Paleo) to 262 now.

    My LDL is too high, my HDL is lowish (don't know if these were measured or calculated)

    My creatine is highish (it was highish march 2011)

    My urea is highish (it was highish march 2011).

    My GPT has increased to borderline high (was ok both october 2010 and march 2011).

    My triglycerides went from 174 to 282.

    My weight went from 94 (nov10) to 77 (march11) to now 87 – and it seems to slowly rise.

    My CFS/FMS symptoms have leveled, but refuse to get better.

    Bottom line of what I want to say: Paleo (as done and understood by me) is not the solution for all health problems. The problem is, when it is tooted as a solve-it-all solution, people who don't improve either desperately seek to "do it better" and get paranoid about nutrition. Or they end up saying "Paleo is crap". Maybe my experience is a 1 in a 100, but still there are people out there whose health problem disappear by going Paleo. It maybe a very small minority, but they are there.

    I feel abandoned by evidence based medicine with the widespread disinterest to find out what is causing CFS or FMS. And while I don't think the Paleo movement can solve this, I don't think the Paleo movement is interested if there are people out there who are not helped by Paleo.

    Obviously I am critical because Paleo did not help me like it helped the Paleo poster boys. I'm a bit at ropes end here.

    While I think some of the things Don Matesz says are BS, I have to think of his experience and am considering at the moment making dietary changes, possibly "away" from Paleo, if only temporary. Maybe more "safe" starch. One thing (that some consider Paleo anyway) which I haven't tried yet is (intermittent) fasting. The other thing would be to try more something akin to the Kitavan diet with less meat. I don't know. As I said, I'm at my ropes end. I know evidence based medicine does not have the answers, because they haven't asked the right questions. The Paleo movement sure hasn't got the answers. When it comes to Nutrition, I am the 1%, I fear. What works for the 99% doesn't work for me – be glad if it helps you and many others.

    Maybe this is all temporary, and I should simply wait.

    "The plural of anecdote is not data and even the most intuitively obvious medical beliefs must be tested"

    I am mildly optimistic that people who have positive experience with Paleo will more and more make their way into science. But I shudder to think of the doctors who will see Paleo as a solve-it-all solution. It used to be: "You need to eat less and drop the saturated fat! If you are not loosing weight, you are lying to me and you are not able to curb your hunger and still eating sat-fat!". What will it be in the future "You need to drop the carbs/grains/whatever. If you are not loosing weight, you are lying to me and you are still eating carbs/grains/whatever!"

  8. One more thing, ontopic this time:

    I sometimes run into people describing "thyroid hormone resistance".

    Looking this up, i found there is a one clearly defined disease called "Thyroid Hormone Resistance", which is caused by genetic mutation and is very rare (1 in 40.000 or less).

    And then there is the fuzzy quack "phrase" of some supposed "thyroid hormone resistance", that gets thrown around when patients respond "poorly" to thyroid hormone. From your description, that would be patients that have problems that aren't caused by the thyroid in the first place…

  9. @Tony
    I would not feel so bad about diet failing to help you. Your experiences are truthfully very common. The common experience is for diet to make a relatively small difference in wellbeing. The internet and their diet gurus are a teeny tiny little bubble world which does not reflect the great big wide real one, where things are FAR more complex, than whether or not you are eating a paleo food item or how many carbs you ate or whatever.

    I am one who has had a "miraculous" transformation by changing my diet and even I always try to get people to understand these disorders are not caused by diet, most of the time diet only helps by circumventing or modulating the disorder.

    Sometimes illnesses are caused directly by diet, but most of the time this is a gross oversimplification and there is a complex set of predisposing/other factors. For example, dietary allergies; it is not as simple as "non-paleo food being bad", you have an issue of immunological dysfunction (which in turn has a lot of other causes) and an issue perhaps of genes adapted to one environment finding themselves in a novel one (dariy intolerance is very common precisely because so many of us come from environments which are naive to dairy).

    Oh and I would avoid any and all alternative medicine diagnoses like "adrenal fatigue" and "thyroid resistance". They are clearly bullsh*t. Unless mainstream medical science and research can provide at least some evidence, however controversial, for these illnesses, avoid them at all costs. For example the fake illness "adrenal fatigue" seems to actually describe the normal physiological response to stress, combined with psychic emotional exhaustion. Real life medical adrenal gland failure has symptoms polar opposite of this so called "adrenal fatigue". There will never be a case where the adrenal glands make "too little hormones" and the person eats more, gains weight, feels tired and cold and has low blood pressure but is otherwise fine.
    On the other hand, this is expected of being excessively stressed and sleep deprived with a grossly in tact adrenal function (except the low BP but that can easily just be idiosyncratic variation - I have very low BP, many women do as well, having low BP doesn't mean you're MINUTES FROM ADDISONIAN CRISIS OH NOES).
    It is a cardinal sign of lack of adrenal gland hormones (and high central ones) to exhibit anorexia, hypoglycemia, and weight loss. The idea that "adrenal fatigue" is behind an obesity epidemic or failure to lose weight is nothing short of medically ridiculous.

    Many of these altie quack made up diagnoses seem to just totally disregard the normal established endocrinology of the body, how tissues and systems are regulated and the function of various hormones at their inception.
    They are almost as bad as obesity researchers, lol.

  10. Out of curiosity, are there any dietary interventions that help optimize thyroid functioning(besides the obvious increase in carbs), or deficiencies that stifle the thyroid (besides iodine)?

  11. Sheesh. Busy week. @Tony - anyone who promises the paleo diet as a cure is lying, particularly for longstanding and complex medical conditions. I've had some people ask me about it for chronic fatigue in particular. I say, look, in my experience some people have had a modest improvement in energy, and often an associated weight loss if there is some extra fat on board already. Clearer skin also seems to be fairly consistent. I know there are anecdotes on the internet of magical cures but I've not seen one in person.

    psychic24 - selenium comes to mind. I'm brushing up on my thyroid textbook so I'll keep a look out.

  12. I have a question---a friend and I were discussing this post, as we were a little confused. I have a relatively mild case of hypothyroidism and PCOS. After going paleo, I was able to stop taking Metformin, and the diet in general has worked wonders for me. My friend, on the other hand, has a big thyroid problem (had her thyroid removed and is being treated by an endo who has her on a T3/T4 combo).

    So we were looking at this and wondering what paleo-related dietary advice (particularly for someone with a bum or no thyroid) would be:

    "Starvation, fasting, or a very low carb diet can tend to lead to low TSH, normal or slightly elevated free T4, and low T3. There is nothing wrong with the thyroid and this is not "hypothyroidism" per se, but a normal physiologic response to perceived starvation, and it should resolve without other intervention once someone stops fasting or increases carbohydrate intake."

  13. @Salima, fasting, starvation, and VLC affect the thyroid via a hypothalamic mechanism (I'll go into this I think in more detail in future posts). In short fasting downregulates the production of thyrotropin releasing hormone (which would lead to low TSH, lower T3 and lower T4). Refeeding and leptin will reverse this. Again, these findings overlap with the concept of adrenal fatigue and do low carb diets cause hypothyroidism, etc. I would say, just be sensible. I wouldn't do a ketogenic diet all the time unless I had a really good reason (like a seizure disorder or brain cancer). Moderately low carb diets are probably fine for nearly everyone. If you are taking exogenous hormone anyway its not as if the hypothalamus can tell your nonexistent thyroid to produce any less hormone, so you don't need to worry so much.

  14. Thanks Emily! I guess my only remaining question is, what do you consider a really good carb source? I know I do far better away from grains myself.

  15. I like starchy root veggies and fruits, myself. Sometimes rice, but only once or twice a week, personally.

  16. Small point... people on oral thyroid hormone replacement are still vulnerable to physiological hypothyroidism from very low calorie diets, very low carb diets, and hypoleptinemia.

    Decreased TSH is one mechanism this physiological hypothyroidism is inducted but conversion of T4 to free T3 is also inhibited, which is the primary mechanism... and people on thyroxine are just as vulnerable, unless they are taking armor to mask this process.

  17. You should read ray peat's articles on thyroid. He believes most hypothyroid people can't convert t4 to t3 efficiently and t4 by itself can make the problem worse. He also thinks the test for measuring thyroid levels are bunk for the most part, they can help to show what may be going on but they don't tell the whole story. Body temp/pulse and achilles reflex test are the only accurate test in his opinion.

    I would venture to say though that the majority of people who receive benefits from thyroid medication in regards to depression could achieve the same effects with a high sugar, high protein, low PUFA, pro thyroid diet like peat outlines.

  18. Woo - the answer regardless would be to eat more carbs. I know Paul Jaminet already covered some of this but I will be doing some more detailed stuff.

    Rip - Peat has some interesting ideas, but I've seen him write with great authority on a few subjects he clearly had absolutely no experience with, and so I don't trust him at all. However, it is a fair concept to reduce PUFAs by eating more starch and sugar.

  19. People have different reasons to have a under-active thyroid. Hashimodo is wide-spread and it is an autoimmune decease. All my autoimmune conditions went way better on a LC diet(since Nov.2007) which I use to manage migraines.My thyroid function didn't get worse after changing my diet. I can give an access to my medical records to Dr. Dean if she wants to see at least one proved case of eliminating all asthma medications on a Paleo diet. I also stopped having seasonal flues and any infections. I have not been seek since I started LC with anything . I understand it may be not be called "the cure" in a strict medical sense , just a remission.

  20. "but I've seen him write with great authority on a few subjects he clearly had absolutely no experience with, and so I don't trust him at all."
    @Emily- Care to elaborate?

  21. Optimizing thyroid function is always a tricky mess. There are so many variables that I doubt lab tests are even accurate (unless you really have a high TSH). It's interesting when you read the works of Dr. Broda O Barnes and Ray Peat who both have come to a conclusion that hypothyrodism is a world wide epidemic and that traditional means of diagnosing it with blood labs are very unreliable. They're both into determining it through body temp and pulse.

    I don't think that everyone should be given T3 but I think that optimizing thyroid functionality is key to a better mental health.

  22. @rip -- one article that comes to mind immediately is the one on MAOIs. He is factually correct (more or less, though overall the evidence for MAOIs isn't quite as good as what he portrays), but clearly has no clinical understanding of the difficulties and side effects of being on an MAOI.

  23. Well you can add me to the list of people who responded poorly to t3 alone. I didn't experience hyper symptoms though, more like comatose

  24. I have normal thyroid levels but my Psych Dr wants to put me on Cytomel 5 mcg and Synthroid 25 mcg to help with my depression. Is this common and safe?

  25. I found your article fascinating. Here's why:

    I suffer from severe depression onsetting around puberty (I turn 30 next month). About four years ago I officially decided to seek help through psychotherapy in conjunction with seeing a psychiatrist. My depression never hits a 'high' - I don't really cycle out. I have bad days and I have worse days (I don't know if this is just a result of years and years of untreated depression). My psychiatrist put me on a number of antidepressants (about a dozen or more, including Lithium, MAOIs and tricyclics when the standard ones didn't work). He finally prescribed T3 (50mcg once a day). It worked. It fixed my depression, my mood, my energy (I describe it like I feel like I 'woke up'). The kicker is that is totally skews my thyroid (I have a normal thyroid in all tests). I end up with a fully suppressed TSH and triple to quadruple my T3, but I present symptomatically *healthy*. No depression, no anxiety, no heart palpitations, nothing.

    My endo has tried to play with the dose to see what happens, but it seems less that 50mcg and I start to experience symptoms (not as bad as without completely, but definitely a noticeable drop). Thankfully my endo and my psychiatrist are fine to prescribe it, but I'm hunting for information because most doctors look at me like I'm nutty when they see my thyroid #s.

    I wish I knew what was wrong with me :-/

  26. Great article. Having a family history of hypothyroidism and coupled with very stressful events - I found myself severely depressed to the point of suicidal. My blood tests showed normal thyroid but other symptoms including, depression, dry-skin, low body temperature indicated otherwise. I found a rarity in a doctor who treated my symptoms - and not my blood tests. After 2 weeks on a combination of T3 and T4 - my depression eased - I woke up and my world went from black and white to colour. For people who want support and look more deeply into this I recommend visiting :

  27. As a 39 year old female, I have been back and forth with my physician about significant weight gain over the years about 70 pound in 5 years. It has been and up and down battle; even with consistent exercise and 85/15 diet I still have difficulty loosing. To top that off, I thought I was suffering depression, but I resolved that mostly with progesterone replacement, and thought we would try to remove the T3 of 75mcg a day slowly since all it did was suppress my thyroid and didn't really resolve the symptoms. 3 weeks off the Cytomel and the mood sneaks back along with the inflammation and swelling - I get my thyroid tested. TSH 4.8; FT4 .6; FT3 3.8 and now I am back at square one again. I did the traditional T4 replacement to only find my levels never stable and high reverse T3. I think I will let him try the T3/T4 therapy that I was hesitant to try. After reading your postings, it looks like a smaller dose therapy might help. They always start me out so high and I metabolize medications so slow that the side effects always make me quit first. I am glad that I have found this site. After visiting with my psychiatrist, I sometimes think she knows more than my endocrine doctor.

  28. I've come to believe that I have lifetime depression stemming from childhood. After a parental loss 7 years ago, I experienced severe symptoms but didn't identify them as depression. Instead, based on my symptoms (cloudy thinking, slow metabolism) I convinced myself that I had hypothyroidism and found a dr to prescribe Armour Thyroid (T4/T3). It helped greatly to alleviate the symptoms and I still take 90mg a day today.

    I have never tried any other treatment for depression, but I have been a cardio exercise addict (30-60min of running daily) for over 15 years (after quitting smoking). I believe that I have been able to keep my depression under control with this combination regiment, but am resentful that I am unable to "cure" myself and of my cardio addiction.

    I believe that in depression, the body reduces T4->T3 conversion in order to conserve resources which lowers seratonin production. T3 therapy raises seratonin the same as anti-depressants. Cardio exercise also stimulates seratonin, which explains my addiction, although many other short acting drugs (nicotine, caffeine, codine, oxy, xanax and heroin) can do the same, causing endless addiction issues for depressives trying to restore the seratonin they crave...

    I'm scared to change my regiment, but would love a permanent drug-free cure...

  29. I am thankful to have found your article. My thyroid was completely removed in Feb of 2012 due to cancer. I've been on t4 supplementation and have been depressed since then. My doctor told me I had "gone through a lot" and was depressed because of that. My weight is climbing rapidly even with little changes in my eating habits. (I'm 32 years old, btw.)

    After combing through message boards I started looking for info on the relationship between t3 and weight gain then inadvertently started finding information on t3 and mental health. I am trying to arm myself with as much credible info as possible for my upcoming doctor appointments. I've already been shut down when I mentioned a t4/t3 conversion issue. I will be seeing a Psychologist soon regarding my depression, although they cannot prescribe t3. I'm hoping one of my doctors will really listen to me and help me. I'd be happy if they measured my t3! TSH is low normal and free t4 is in range.

  30. My endo's new book has appeared:

    Based on his many years of experience using T3 (in combination with T4) to treat hypothyroidism, the book's chapter on depression has some interesting observations.

    1) Many depressed people with "normal" TSH respond very nicely to a trial of thyroid hormone. If continued on optimal T3/T4 therapy, many can avoid or discontinue antidepressants.

    2) Prozac appears to suppress TSH, but lower T4 at the same time. This will seem paradoxical based on standard thyroid theory. He believes that Prozac stimulates the major deiodinase enzyme, thereby increasing T3 at the expense of T4. In the pituitary, however, the elevated T3 suppresses TSH. This may explain why Prozac often seems to help in the first few months, due to the quick peripheral T3 boost, but then "stops working" as tissue level T3 falls due to both the reduced T4 levels and the lowered TSH (TSH stimulates the deiodinase enzyme). He seems to be proposing a novel mechanism for antidepressants involving thyroid physiology. Very interesting.

    3) Psychiatrists have had the most experience using T3 in the decades since using T3 for thyroid replacement quickly died out after it became available as Cytomel. It often helps depression, but "the psychiatrists have been even worse than the endocrinologists in terms of figuring out the proper dosage." The huge overdoses commonly used typically help initially but then fail as tissue levels surpass optimal.

    4) So, many depressed people fall into a "black hole." Doctors won't do a thyroid replacement trial due to a "normal" TSH. They get put on antidepressants that further suppress their TSH and don't work very well because they don't address the underlying thyroid problem. Now it's even less likely any doctor will dare give thyroid hormone and they're stuck.

    The other chapters are just as interesting!

  31. Very interesting. I'm a thyroidectomy patient. Originally admitted for parathyroidectomy due to high calcium levels, during surgery a lump in my thyroid isthmus was found and removed. The lump proved malignant, and a complete thyroidectomy was scheduled. Post surgery I felt weak, tired, slept often, and by 5pm everyday was yawning and listless. Brain fog, cognition, executive memory (was tested)......all sorts of tired and fatigued. I complained to my Endocinologist. She suggested age related and other factors. But the fact is I was high energy before surgery. After recovery - never the same. This was 1997.

    About 3 years later I was preparing for another radioactive iodine scan to ensure all was well. This scan (I had been scanned post surgery and at least one other time) I was taken off synthroid and put on Cytomel for a period of 2 or 3 weeks (took a long time for my hormone levels to drop). During this time of Cytomel I felt great. I happened to be in seeing my PCP for a physical and told him I was feeeling great. He inquired about my meds and said I should tell my endocrinologist. I didnt see her until 6 months after my scan and totally forgot about it having succumed to life of feeling awful. Tow years later I dated a female MD. She observed that I was pooped out and fatigued all the time. I told her my story and she researched for any medical info. She gave me a printed study that appeared in the New England Journal of Medicine. Bottom line was that many patients who feel bad on T4 alone, feel much better on combination therapy.

    I gave the info to my endocrinologist and she reluctantly did the combo. I feel better - but she still doesnt believe its anything but a placeo. Just my two cents.

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  33. I am curious to know if psychiatrists using a T4/T3 treatment for depressive patients recommend long-term treatment, as opposed to short-term, perhaps cycling on and off in 3 month intervals. Is there any danger that long-term treatment of eurythyroid patients might permanently alter thyroid function, leading to a situation where life-long thyroid treatment becomes necessary?


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