A streamlined stack of supplements designed to meet your most critical needs - Adapt Naturals is now live. Learn more

Three Reasons Why Your Thyroid Medication Isn’t Working


Last updated on

Reviewed by Jessica Montalvo, MD

This article is part of a special report on Thyroid Disorders. To see the other articles in this series, click here.

In 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.

Want to learn more about thyroid disorders?

Download This Free eBook

Find out how a thyroid imbalance could be causing your biggest health problems.

"*" indicates required fields

I hate spam, too. Your email is safe with me. By signing up, you agree to our privacy policy.

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 (please note, “HPT” stands for “hypothalamus-pituitary-thyroid axis”):


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 HPT axis. (1) 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. (2) 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.

Like what you’re reading? Get my free newsletter, recipes, eBooks, product recommendations, and more!

Second, inflammation decreases both the number and sensitivity of thyroid hormone receptors. (3) 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. (4) 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. (For more on how to address underlying inflammation, check out this episode of Revolution Health Radio with Izabella Wentz.) 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.

ADAPT Naturals logo

Better supplementation. Fewer supplements.

Close the nutrient gap to feel and perform your best. 

A daily stack of supplements designed to meet your most critical needs.

Chris Kresser in kitchen


Join the conversation

  1. Hi Chris,

    I can’t find anything to read about why I am on synthroid, taking it properly and nearly every TSH check I am way hypo such as once 40, then they raised synthroid and soon normal labs again and this August 8.8 and raised to 175mcg and today I am 0.8 but was sent for a second ultrasound the first one was called for in the middle of my exam which was very hard to get through. I can’t even wear a necklace and basically since being diagnosed at about 25 with TSH 10 as hypothyroid after the onset of spine and bone pain that is now severe fibro and a multitude of other problems after growing up so healthy I am so nervous someone is missing something critical but I have fought to look and grown tired and fought again back and forth. Since 2009 the thoracic pain became acute and severe and chrnoic and it never hurt in that area before and hasnt stopped since I even raced for a breast reduction it was so bad. That didn’t take away the pain. On accident they found some “borderline to lymphadenopathy”nodes in my axilla and mediastinum and two shapes in my right lobe of my right lung. I have just moved to San Antonio and my new PCP who sent me for thyroid US will get the results comparing to the one I had in 2008 I dont remember much but there were nodules and a goiter and the middle was thick, im following up on so many things I dont remember what they said except keep taking your synthroid whih I do exactly in the am no food or other meds until 30 minutes at least yet it keeps crashing with no other changes- having the US tech stop in the middle of my test today to call the doctors office in Tyler to obtain the former radiology report scared me- im not an idiot I was just without insurance for a long time when I got sick. My father has non hodgkin lymphoma mantle cell right now, his mom died of leukemia and had five other cancers, An oncologist followed me with repeat CTS which I am past due on another look was supposed to check 2 years ago for any changes and a recent breast mam us and mri detected two lymph to watch as well……. meanwhile my youth is slipping away and i have tried to stay so upbeat. I live in severe pain that went from managable fibro to severe in 2009 and hasnt stopped or responded to anything i have tried it all- I am on 12 drugs none of which have changed during t his last thyroid crash. i run fevers with flares of pain- I flush I feel hot and I run about 101.2 and can tell to go check for fever based on the pressure I feel I have descibed my pain as pressure for so long- my husband keeps telling me one day someone will figure it all out- but I dont know who HOUSE was a tv show……..excuse the typos normally i would correct but im tired and just had my throat smashed in a US and have no idea what I will find out next or do next…… My mother has Graves and had her thyroid Killed with Iodine- her mother had a cyst removed and was military and doesnt remember much about it but my mother does not have the pain and the other things I am going through- my husband was dressing me when I was first diagnosed and once when my TSH was checked while Iwas so sick my white blood cells were at 16 not too high but the TSH was 40…… very hypo I am one tough cookie but tired of thinking and i guess if all along its been cancer, then its too late, isnt it?………..My recent WBC count was only 12 at the time of TSH 8.8……..my hypo is -NOS anyway I liked reading your article but still dont understand whats going on and or why these highly educated specialists havent made me well or at least improved me… I have only declined this last year and my child is 6- i only keep fighting for her and I can feel my thyroid choking me but also feel the difference of recent labs TSH 0.8 from Augusts 8.8- at least im not crying everyday and now I can move. Sincerely, Tuesday- PS I have no idea what to expect from todays US I guess we will find out

    • Hi Tuesday
      A few things to google
      Reverse T3, hashimotos, STTM, adrenal fatigue, iron defiencies and thyroid/cortisol, vit d and thyroid/cortisol, natural dessicated thyroid (NDT), cymotel, the gluten connection. The best medicine is to learn yourself what is going on and how it works. We heal ourselves with the assistance of doctors.,

  2. 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 drhuggins.com)– 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

    • 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.

  3. Hi,

    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.

  4. 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.

  5. 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…..my 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…

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

  11. 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?

  12. 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.

    • PS I apologize to leave three comments but I also forgot to mention that a few years ago, when I first became extremely sick, the city broke a sewer line and my basement apartment was flooded with about 2 ft of raw sewage. The home was built in 1900. They did replace the carpeting but not the wood paneling or the laminate. I cannot move. I have no way to get a new apartment. My landlords are being very generous because I’ve lived here for 8 years now. But I don’t know what to do. I truly believe the sick feeling I’ve been having is from this sewage spill since the main symptoms I have began shortly after that. But the doctor said it’s nothing but thyroid. I even had one doctor tell me I must have been evil in a past life, (not joking) and another who laughed at my red face and said I’m sorry..it’s just…….your acne….it’s so bad. I am at a total loss. Please if you have any way of sifting through my comments *I left three, sorry) and all I’m looking for really………is what direction can I take to at least feel better? Who can help me? What should I do to make this easier to relay all of this information without overwhelming them and coming across as a hypochondriac? What is the most beneficial way for me to communicate all of my symptoms and issues in an efficient manner that will allow them to look at all possible causes? I have been tested for Lyme disease and autoimmune disease and they have ruled out MS and diabetes, as well as Chrons and Lupus

    • Also if I have the antibody to MCV is that a possible reason for the inflammation on my face as well as my overall ill feeling? Low grade fever, feeling just very ill. It seems to generally coincide with the inflammation on my face. So is this likely a thyroid problem or a viral?

    • Also if I have the antibody to MCV is that a possible reason for the inflammation on my face as well as my overall ill feeling? Low grade fever, feeling just very ill. It seems to generally coincide with the inflammation on my face. So is this likely a thyroid problem or a viral?

  13. 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.

  14. Lin,

    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.

  15. 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

  16. 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.

  17. 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

    • Dear Tracy, (How) did you ever resolve the issue when increasing thyroid hormone your muscle ache. (My muscles in addiditon get stiff /weak) I am on 2.75 grains of armour thyroid (and have tried nature thyroid also) . My doc has also tried me on a little bit of Cortif for adrenal fatigue with no results. Susan

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