Three reasons why your thyroid medication isn’t working

July 1, 2010 in Thyroid Disorders | View Comments

medicationIn the last post I explained that, for the vast majority of patients, hypothyroidism is an autoimmune disease. This isn’t just an academic distinction. It’s the reason both conventional and alternative treatments are so often ineffective.

In this post I’m going to show you why taking replacement thyroid hormones without addressing the underlying immune imbalance is doomed to fail.

The ultimate effect of hypothyroidism, whether it’s caused by iodine deficiency or autoimmunity, is to decrease the amount of thyroid hormone available to the body. The conventional approach is to simply replace these hormones with either synthetic or bio-identical forms.

On the surface it seems like a reasonable approach. Patient doesn’t have enough hormones? Give more hormones. Simple, right?

Not so much.

Once again the conventional approach falls short because it ignores the underlying cause of the problem. It’s like taking Advil when you’ve got a pebble stuck in your shoe. It might work for a little while, and might even be necessary to dull the pain. But you’d be a lot better off if you took the pebble out of your shoe. Right?

Let’s take a closer look at why thyroid hormones often don’t work, or stop working over time. The following diagram illustrates how autoimmunity affects thyroid metabolism:


Immune dysregulation is another term for autoimmune disease. We still don’t know exactly what causes it, but most researchers agree it’s a mixture of genetic susceptibility and environmental factors such as iodine (excess), infection, pregnancy, diet and intestinal permeability.

In autoimmune disease the body attacks itself. It does this the same way it attacks foreign invaders like bacteria and viruses: with T-cells, B-cells, natural killer cells, and cytotoxic T cells. The immune response also involves proteins called cytokines, chemical messengers that pass messages between cells.

This self-attack by the immune system increases inflammation. And inflammation has a profound effect on all aspects of thyroid metabolism and physiology.

First, inflammation suppresses the hypothalamus-pituitary-thyroid (HPT) axis. One study showed a single injection of the inflammatory cytokine TNF-alpha reduced blood levels of TSH, T3, free T4, free T3 and TRH for 5 days. This shows inflammation disrupts the production and regulatory mechanisms of thyroid hormones. Thyroid medication will increase the levels of T4 (and possibly T3), but it doesn’t address the other effects of HPT axis suppression.

Second, inflammation decreases both the number and sensitivity of thyroid hormone receptors. If there aren’t enough receptors, or they aren’t sensitive enough, it doesn’t matter how much thyroid medication we take. The cells won’t be able to use it. It’s like when my grandpa used to turn down his hearing aids while he was watching the football game. It didn’t matter how much my grandma yelled at him – he couldn’t hear a word she said.

Third, inflammation decreases the conversion of T4 to T3. T4 is the inactive form of thyroid hormone. The body has to convert it to the active T3 form before it can be used. Most synthetic hormone medications on the market are T4. If you give a T4 medication (like Synthroid, Levoxyl, Unithroid, etc.) to someone with inflammation, it’s not going to work because they can’t convert the T4 to T3.

Patients who don’t convert T4 to T3 well do better on bio-identical hormones like Armour, because it contains both T4 and T3 (in a 4.22:1 ratio).

Inflammation disrupts thyroid metabolism in several other ways, but I think these three examples make the point.

Now let’s review.

Inflammation causes HPT axis disruption, decreased receptor function, and decreased conversion of T4 to T3. Thyroid medication only increases the levels of thyroid hormone (usually T4) in the blood. No matter how much we take, it’s not going to restore HPT axis coordination, improve receptor function, or increase conversion of T4 to T3.

The only way to do that is to address the problem at its root by regulating the immune system and decreasing inflammation. Unfortunately, this is rarely done in either conventional or alternative treatment of thyroid disorders.

Before I sign off, I just want to make one thing clear. I’m not saying thyroid medication isn’t necessary or useful. In fact, I think it’s an important part of treating Hashimoto’s – especially when TSH is consistently elevated and T4 and T3 are consistently low. My point is thyroid medication is only one piece of the puzzle, and it won’t be effective on its own unless the autoimmunity and inflammation are addressed.

If thyroid medication is the fantasy magic bullet of conventional medicine, iodine is the equivalent in alternative medicine. In the next post I’m going to explain why supplemental iodine may cause more harm than good in Hashimoto’s patients.

  • Jamie

    Great series Chris.  Just a quick question regarding iodine (and I appreciate you are busy atm so no hurry).  While I can appreciate that simply throwing large doses of iodine at the thyroid problem may be an issue (people need to realise that often having too much of something can cause exactly the same sorts of issues as not having enough – iron is the classical example), what are your throughts for those who live in known iodine-deficient areas.  I am based in New Zealand and most of our soils are very low in iodine and iodine supplementation has recently been strongly recommended for all women planning a pregnancy in New Zealand and along the eastern seaboard of Australia for this very reason.  Thanks of ryour preciosu time in advance.

  • Jesse

    I’m confused. In the last post you said that depressing the immune system was worse than the disease it would be treating:
    “But in the case of Hashimoto’s, the consequences – i.e. side effects and complications – of using immunosuppressive drugs are believed to outweigh the potential benefits. (Thanks to conventional medicine for a relative moment of sanity here.)”
    But in this article, you say it is unfortunate that this treatment is rarely done.
    Which is it? Am I misunderstanding something?

  • Chris Kresser


    There’s a difference between suppressing the immune system across the board with steroids and dampening the parts of it that need dampening.  And there are many ways to reduce inflammation that don’t involve immunosuppressive drugs.

  • Chris Kresser


    I’m going to cover iodine in detail in the next article.

  • Jesse

    Oh, ok. I guess you haven’t gotten to that part yet.

  • claire

    I’ve been reading your blog with interest, being uninsured and only able to access my naturopath when I can pay out of pocket. What you report makes me think I’m generally on the right path towards keeping healthy and healing myself as I get older. Here’s my question.
    Will you be talking about the tests to determine the need for iodine? My naturopath suggested I take one and I was put on iodine after that.
    I wonder about all the immune system problems I’ve developed as I’ve moved through my 40′s: Allergies, mild asthma, tinea versicolor, mild eczema, thyroid problems, the list keeps growing.
    I still feel energetic and mostly fine but I can’t help but get stressed out trying to figure out how to keep healthy. What should one do if it seems that their immune system is out of balance? Thyroid is just part of it. A very important part according to this article. Thanks

  • Sarah

    This series is amazing thank you!!!  I was diagnosed with Hashimoto’s a year ago from an antibody blood test even though my TSH was normal I was put on Synthroid.  I also suffer from Chronic Idiopathic Urticaria and take Reactine daily to control the hives.
    I am very curious about your next segment as I would love some tips on addessing the autoimmune part of this as I clearly am suffering from two autoimmune diseases, all which came on after the birth of my second daughter.
    I would love to know what you think about high cortisol levels and its effect on thyroid hormones, more specifically the conversion of T4 to T3 and/or antibodies that could be faciliated by high cortisol?  I can remember being 18 years old and put on the birth control pill and having all the symptoms of hypothyroidism after about a year on the pill, but all my labs came back normal (aka my TSH was normal) except my cortisol was very very high.  Dr said this was normal on the birth control pill.  About 6 months after that at a clinic a different dr said my thyroid felt firm and to get it checked out.  I was 19 and stupid and did not.  Since then I have steadily had increasing problems with weight gain, acne, fatigue, allergies, and now hashimoto’s and hives.  Seems connected in my mind but I would love your thoughts…when you have time of course :-)

  • Chris Kresser


    I wish there was an easy answer to your question. Unfortunately, autoimmune disease is complex and each case must be considered individually. That said, I’ll be providing some general steps to regulate the immune system and reduce inflammation that are applicable to everyone. Stay tuned.

  • Chris Kresser


    Birth control pills increase thyroid binding proteins, which in turn decreases the levels of free thyroid hormone (the active forms) available to the body. This won’t turn up on a test unless free hormones are measured, which they rarely are. That explains why you had hypothyroid symptoms on the pill, but had normal test results. Cortisol is a hormone that is elevated during an active stress response. Stress is inflammatory. Inflammation reduces T4 to T3 conversion, dysregulates the HPT axis, and decreases receptor function.

    So yeah, it’s all related.

    In a later post I’ll be talking more explicitly about problems that cause hypothyroid symptoms that won’t show up on normal lab tests. I’ve just mentioned one (increase in thyroid binding proteins), but I’ll go into more detail on that and talk about a few more.

  • Sarah

    Thanks!  I look forward to your next post :-)
    In reading some more on cortisol and the birth control pill, it seems common place that cortisol is high on oral contraceptives.  Even my lab requisition says it will only test cortisol if patient is confirmed to not be on oral contraceptives.  Could this be a partial link to why so many women suffer from hashi’s?
    Also, to whomever was saying iodine is not an issue…I work as a Nuclear Medicine Technologist and we test the thyroid gland function by giving the patient a very very small dose of radioactive iodine.  We can then measure, with a radiation detector, how much is in the patient’s thyroid and how much is still circulating in their body.  If the patient consumes even seafood (which relatively speaking is low in iodine content) in the 3 weeks prior to their test, it skews the results a lot!  They actually look like their thyroid is hypofunctioning because their thyroid is so full of iodine (for lack of a more medical description) that it won’t take up the radioactive iodine we give them.  So essentially by having them on a no iodine diet 3 weeks prior to the test we can then get a snapshot in time of their thyroid function.
    Just FYI

  • kara

    Hi Chris-
    My husband had hyperthyroidism, which has treated by irradiation. Now he has hypothyroidism and takes Synthroid. Since he thyroid was deliberately damaged, and it isn’t an autoimmune problem, is synthroid his only choice?

  • Chris Kresser

    Since your husband can’t produce thyroid hormone on his own, replacement is his only choice. That said, are you certain he didn’t have Graves’ disease? Graves’ is the autoimmune form of hyperthyroidism. If he had that before, he likely still has it now and it would be important for him to address the autoimmunity.

  • kara

    Thanks, Chris.  Not sure or not if he had Graves disease. Would the doctor have tested and mentioned that? Is there anyway to test that now?

  • Chris Kresser

    It’s entirely possible the doctor didn’t tell you, because it wouldn’t have altered the course of treatment.

    Your husband can have his TSH receptor antibodies tested.  This is sometimes called a TSI test, or a TRAb test.  If these antibodies are elevated, it’s likely he has Graves’.  TPO & TG antibodies are also often elevated, as they are in Hashimoto’s.

  • Alisa

    I’m personally interested in this series, and hope that you will also be addressing your take on how to ” dampen the immune system and decrease inflammation.”

  • Kathy

    What do you think of treatment with Cytomel? It’s T3 only. My concern is that I might need some other thyroid fractions (T4, perhaps T2/T1) as might be found in Armour. Thoughts? 

  • Chris Kresser


    I’m sorry, there’s really no way I can answer that question without doing a full exam and lab work.

  • hans keer

    Eric, I did not study this subject, but my first reacting would be that “dampening” (reducing) the immune system is not a good idea. How would you like to do this and what would be the other effects of this. I would suggest that people try to find and avoid the things that are causing the auto-immune reactions. Illiminating foods like grains (, soy (, dairy and (perhaps) eggs would be a good start. Are you going to continue on this subject?

  • Chris Kresser


    Removing potential immune triggers is important. I will discuss this further. But often that’s not enough. Most autoimmune patients have a Th1/Th2 imbalance that must be addressed. This is what I mean by dampening the immune system. “selectively dampening” or “regulating” would have been more accurate terms.

  • hans keer

    Btw, sorry for calling you Eric. Don’t know where that came from. A mental derangement perhaps :-) . OK, I’m curious about what you are going to say about the triggers. VBR

  • Mario

    First, I know no better medicine to regulate Th1/Th2 imbalance than LDN (low dose naltrexone).

    Second, I think that avoiding some of the immune triggers/endocrine disruptors is almost impossible in our modern society. How one can avoid bromine, bisphenol and other hazardous compounds present in dust, devices, cloths, foams, carpet, furniture, cars, etc, etc, of almost any ambient of any city around the world?

  • Lethal Lee

    “Patients who don’t convert T4 to T3 well do better on bio-identical hormones like Armour, because it contains both T4 and T3 (in a 4.22:1 ratio).”
    Correction Armour is NOT bio-identical. It is natural, that is, it contains Thyroid Hormones (all of them), made naturally by the pig’s thyroid.
    The synthetics ARE bio-identical but are not natural.
    Note I am NOT saying synthetics are better certainly T4 alone is good for no-one IMHO. I tried NTH unfortunately my conversion is lousy. I do very well now on T3 only.
    Note Armour since reformulation doesn’t appear to be effective for many folks anymore.

  • Chris Kresser


    Regarding Armour’s reformulation, one reason some patients do worse on it now (and others do better) is that they changed the fillers. It now has calcium stearate, dextrose, microcrystalline cellulose, sodium starch glycolate, and opadry white as inactive ingredients. Many patients with Hashimoto’s have polyendocrine autoimmune disorders and react differently to the fillers in different hormone products.

  • Lethal Lee

    Hi Chris,
    Actually all of the ingredients you listed were already in Armour, to be precise they were since the FIRST REFORMULATION in 1996.
    However in 2008/9 they again reformulated by greatly REDUCING the dextrose & greatly INCREASING the methylcellulose.
    I wrote about it here
    So I’m acutely aware that for MANY it is not as effective anymore. Interestingly back in 1996 there was a similar reaction to the FIRST reformulation.
    I’m in Australia & the only Dessicated Thyroid available here is Compounded using PCCA Thyroid Extract USP. Unfortunately the Compounders ALL use methylcellulose or worse Hydromellose as fillers. I’ve had to resort to T3 only because of that & now doing very well.

  • pat & jim

    is there any natural herbs that can be taken.
    how are you tested for hisomito disease

  • Chris Kresser

    You have to have your thyroid antibodies tested to determine whether you have Hashi’s or not.


  • pat & jim

    what are the specialist called that can help my husband
    he gets headaches with most thyroid meds and is now taking shots.

  • Chris Kresser


  • http://healthyskeptic Tracy McCauley

    This article gives me the most plausible explanation to what is going on with me at 14 I was sent to Georgetown university with a goiter I am now 46 and over the last 6 years have gone from .75mcg of synthroid to 4 grains of armour thyroid with no increase in thyroid levels all my muscles ache it’s like a charlie horse in my entire body as well as severe hair loss dry scaly skin abnormal weight gain joint pain and I have trouble maintaining my body temp. it’s like chills but when I take my temp. it’s like 94-90 and I will fall asleep weather I want to or not like hypothermia I was also diagnosed at 25 with reiters syndrom so the autoimmunity issue is also present should I continue letting my family doctor try to level out my thyroid with medication increases and discuss this article with him or am I to a point where I should be seeing an endocrinologist Thank-you for this post it has been most insightful

  • Chris Kresser

    Hi Tracy,

    Unfortunately, you’re unlikely to get the support you need from a PCP or an endocrinologist, unless they are unusually progressive and open-minded. The standard of care for thyroid disorders – whether autoimmune, as most are, or otherwise – is replacement hormone. It’s rare for conventional practitioners to go beyond that and address the underlying mechanisms involved.

    I do work with patients in-person in the Bay Area and by telephone around the world. If you’re interested in that, please check out my professional site.

  • lin

    Each day I take 125mg of thyroxine, 6xmg Norethisterone,
    4-6xtransexamic acid as needed, 250mg Adizem,30mg Lansoprazole. 40mg simvastatin, 6x adcal-d3, 6x 8/500 co codimol, 75mg asprin, 2.5 ramipril, and a weekly 30mg butrans patch for pain. I am exhausted all the time. What can I do instead

  • Chris Kresser


    I’m sorry, I can’t possibly advise without knowing more about your situation. Thyroid physiology is incredibly complex.

    I do work with patients in-person in the Bay Area and by telephone/Skype around the world. If you’re interested in that, please check out my professional site.

  • lynne

    Hello Chris,
    Thank you for your interesting information about Hashimoto’s. I have recently been diagnosed with this and was shocked owing to the generally healthy life and diet i had mainly followed. However, about 3 months prior to the first major symptom showing up I had an agonising root canal procedure which lasted over a month with many visits to the dentist owing to massive infection that had to be treated with heavy antibiotics and the difficulty the dentist had in securely locating all the ‘canals’. Could this be the cause and if so would you recommend removing this? Is there some way of diagnosing this as the cause. I am becoming increasingly tempted just to remove it IN CASE it was the cause, and so there may be some chance to recover from the extremely debilitating symptoms I am suffering.

  • Chris Kresser

    Lynne: autoimmune conditions rarely have a single, isolated cause, and once antibody production begins, it does not stop. That’s the nature of how the immune system works. I don’t think removing the root canal is likely to reverse your Hashimoto’s, unfortunately.

  • Scott Kleist

    Chris, My wife is right in the middle of finding the right doseage of Armour Thyroid with our Dr. How can we determine if her “Thyroid” issues are really being brought on by Immune Dysregulation – is there a test? Like a white blood cell count or something?

  • Chris Kresser

    Yes. Thyroid antibodies (TPO & thyroglobulin). If her doc won’t order, you can get them at

  • Select

    To Lynne:
    I think the heavy antibiotics are much more likely what caused the problem to emerge. I am also very healthy and never had any thyroid symptoms until after I took some strong antibiotics. The ~3 mnths before major ongoing symptoms sounds accurate in my case too.

  • lynne

    Select, yes I have also come to the conclusion that it is the antibiotics that may have tipped me over into Hashimoto’s. I also got tested for mercury toxicity and my levels are in the low end of the acceptable range, so mercury is not the problem. Following advice on one of Chris’ pages I have read Dr Natasha Campbell-McBride’s book Gut and Psychology Syndrome, and she points to damage done to the gut by overload of antibiotics amongst other things, which can trigger auto-immune problems. She has created a diet that seeks to remedy this. You might find that worth looking into.

  • Kay

    Hi, Chris.
    Interesting read. You give the impression (how it reads to me) that taking thyroid “medication” won’t work for most people suffering from hypothyroidism, but how does that explain the fact that most do feel better, improve on it?

    I agree that hypothyroidism is often an effect of another, underlying illness, but you didn’t mention any of them specifically like Adrenal Fatigue, which I think is critical for those who still need a more full, proper diagnosis beyond the low thyroid symptoms (also for keyword searches).

    Nature-Throid by RLC Labs is a natural T3, T4 combination BTW.

  • Summer

    Could Lupron injections I received to treat endometriosis have caused or be correlated to my hypothyroidism? After my Lupron tx was finished I went into my OB because I was feeling miserable…lab work later revealed TSH of 72 and T4 of 0.4. I think I passed off a lot of my symptoms to the Lupron. My PCP put me on Synthroid and two weeks later I still feel lousy! I would think at this point after two weeks of Synthroid I would be feeling better. I also need to start taking birth control to keep my endometriosis from returning, but am worried about further complicating my already messed up hormones! Any information would be very appreciated.

  • Sarah

    Summer…it can take a long time for the Synthroid to start working. Like say upwards of 3 months. We do tests for thryoid at my job and our patients have to be off their Synthroid for a minimum of 3 weeks before the test can be done. It takes a long time to get in and out of your system. I’m not sure about the birth control pill… endo thinks that may have been a trigger for me to have Hashimoto’s. I am sure Chris can explain it better but something happens to your thyroid while on the pill…it depresses it or something…

  • Sarah

    oh! and make sure you are taking your synthroid properly!! Take first thing in the morning, on a completely EMPTY stomach with a FULL 8 oz glass of water. Then wait 1 hour before eating or drinking anything else. Don’t eat walnuts, stomach meds or tums or calcium supplements within 4 hours of taking it.

  • Katherine


    I just found out that I have Hashimoto’s hypothyroidism. I am 34 and not overweight, and have an excellent healthy, organic diet. I think your information is totally awesome and useful, but what is one supposed to do other than take the synthetic thyroid in this case.

    I’ve researched and found that mine could be due to mercury poisoning, so my first step in healing naturally is to get the mercury amalgam fillings out of my teeth and do a mercury and heavy metal cleanse – as soon as I can get the money to do it. I also do not eat carbohydrates, not even whole grains or legumes, and I even don’t do well with caroots, because when I do, I feel awful ALL THE TIME with headache and nausea, even while taking synthetic thyroid medication. I can actually have days where I have tons of energy eating in this way.

    Thanks so much for any info.

  • Kathy

    Katherine — I am a Hashimoto’s patient who has had her mercury fillings removed — and my dentist did not know the proper way to do it! In particular, what he used to replace my fillings was a material I was highly reactive to (not biocompatible with). So I would advise you please, please, please find someone who does the Huggins Protocol — and the best way to be sure you have the right person is to speak to someone on staff at– I say that not because I’m a commercial, but because that is how I got all the materials out of my mouth that were making me sick (more than just Hashimoto’s). I’m confident I’m “on the road” to wellness because getting the noncompatibile materials out is an immense strengthener to the immune systerm. I wish you the very best — Kathy

  • Anonymous

    I have been on thyroid medicine for about 7 months. It took a few months for me to start feeling better but now im starting to feel bad again. My feet get swollen if i set to long and start to fall asleep. I feel like ive been hit by a bus but didnt do anything the whole day. I started my period and it quit in 3 days. So i thought it was done then all of sudden 4 days later i was bleeding so bad i couldnt get off the toilet. I dont have any idea what is going on with me . I thought the medicine was to make me feel better. Please if you have any info. let me know. Also im so tired when i go to bed but i toss and turn all night with usually 4 hrs. of sleep.

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