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Three Reasons Why Your Thyroid Medication Isn’t Working


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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.

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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.

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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.

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  1. First the labwork (drawn Friday):
    TSH > 100.00 u(IU)/mL HIGH (normal range 0.4 – 5.5)
    T4 100.00 u(IU)/mL HIGH (normal range 0.4 – 5.5)
    T4 < 0.5 ug/dL LOW (normal 4.5ug/dL – 12.0 ug/dL)
    T3 Free 0.8 pg/ML LOW (normal 2.4 – 6.8)
    My biggest health issue has been the gastroparesis. I've not had solid food in over 5 years, everything is liquid. I've had feeding tubes, several surgeries, etc and stomach is still essentially paralyzed. I am nauseous most of the time and vomit 5-25 times a day (worse when severely constipated, causing me to throw up bile frequently). Last month I saw a surgeon who specializes in gastroparesis and he said that he wanted to ensure my thyroid levels were normal before he does a colectomy (remove my colon). I am now more concerned about my thyroid though. I can't find any information that is helpful to me online because all the articles are written with the assumption the thyroid is still present. I'm feeling a bit scared. Anyone been thru similar? Or similar labwork? I need hope. Thank you all, Julia

    • I worked for a chiropractor who had a client with that condition. She couldn’t eat food and was severely depressed. At her appointments he rubbed her stomach twice a week for two months and then she didn’t have gastroparesis anymore and could eat food again and has been living a healthy full life ever since. I have him rub my stomach and it helps me so much with bloatedness and diarrhea. He rubs the muscle over your organs that are all tight and notted up. It definitely hurts when he rubs the stomach, but you feel so much better after! It loosens the muscle so that your organs are no longer tight and paralyzed. He practices in Orem, Utah but I bet there is some info about this process online. If your stomach gets healthy, that will probably help your thyroid issues too!

  2. I’ve had symptoms of hypothyroidism since my teens, my first pregnancy at 18 significantly worsened my symptoms. All the doctors I saw continuously monitored my thyroid hormone levels, but they always came back “normal” or “within normal limits.” Over the years the symptoms continued worsen, I was sent to countless psych doctors because all of my medical doctors couldn’t do anything else, I was then treated with a multitude of SSRI’s and anti-psychotic medications which in turn made my whole body malfunction. It wasn’t until the premature birth of my 3rd child in 2004 that I was sent up to Endocrinology who diagnosed me with ‘Post partum thyroiditis”. I was put on my first run of synthroid (25mcg X 90 days). I underwent several other tests in the meantime and my diagnosis was changed to Hashimoto’s Syndrome. At the end of the 90 run my thyroid hormone level was showing “within normal limits” so they downgraded my diagnosis back to post partum thyroiditis, and all medication stopped. I quickly returned to feeling completely run down, which having 3 children under the age of 8 including a preemie newborn, and a husband who was deployed over seas was very bad. I couldn’t lose any of the baby weight despite dieting and exercising, my hair started falling out in clumps (AGAIN), and my skin was so dry and itchy that I wanted to crawl out of it, and to this day I have been extremely constipated. I had to endure all of these symptoms until 2007 when an MD in Germany took pity on me and changed my diagnosis to “Sub Clinical Hypothyroidism” and restarted my low dose of Synthroid. That helped alleviate some of the symptoms but I still never felt “good”. Fast forward to 2010, I had a thyroid biopsy where they found several goiters, but being on my low dose of synthroid my levels were still WNL, so they recommended no further treatment. In 2013 I was assigned to a new doctor who monitored my levels every 4 months, in 2016 she noticed an increase in my T4 level and upped my Synthroid to 50mcg, but the diagnosis of Sub Clinical Hypothyroidism has been continued. We are in April 2017, new doctor, my thyroid level still shows WNL, but I feel so run down that I practically fall asleep while driving, I cannot lose weight no matter how much research I do and drastically change my diet, I even injured myself while exercising. My skin, my moods, my digestive health is a serious mess, the only thing that isn’t happening is my hair falling out at an alarming rate. So the point of my story here is that no matter what the MD’s do or say, I have learned to read my body. I know that my thyroid levels look great on computer printouts due to the supplemental hormones, but ultimately my thyroid is NOT functioning the way it should. After 19+ years of dealing with this I am sad to say that I am at a loss and have little hope of ever feeling like I am functioning “normally” or truly healthy.

    • I have the exact same story of 15 years. I have seen functional integrative doctors with no help. I am at a total loss. Please let me know if anything changes.

      • I would suggest trying the candida diet (Read Tired-So Tired and the “yeast connection” by William Crook, M.D.) and asking for porcine thyroid. Synthetic didn’t work for me. I hope this helps! I’m not where I want to be yet thyroid and energy wise, but I’m making some progress. My tests all came back normal too. My son and I have to avoid all water disinfected with chloramine (not just chlorine, but chlorine and ammonia) in it since it causes us gut inflammation which got us in this mess in the first place. We had to move to a town that uses chlorine to disinfect the water.

    • I have been taking Synthroid 75 msg for 28 years. My HDL levels have remained in the 60s and as high as 70 for the past 18 years. Last year’s TSH was 2.130 and HDL was 63. This week my labs came back and my TSH (for the very first time) elevated to 5.650 and HDL dropped 30 points to 46. My primary care physician has asked that I take a higher dose of Synthroid (100 msg) and repeat the TSH blood test in six weeks. I am very very concerned that something may be wrong with my thyroid gland or pituitary gland. Being highly anxious I cannot wait six weeks. I am seeing an endocrinologist hopefully early next week (a family friend) and ask for his advice. My pharmacist has gone so far as to say that perhaps it was a lab error. But my nutritionist said, “highly unlikely.”

      Please advise.

    • I’ve had hypothyroid for 9 years.. 2 before DX. A few months ago, I started feeling extremely “thyroid” tired. I went to endo- he ran the TSH and T4 all normal. I started to do lots of research – I knew something was off. I went to my gynecologist will a list of test to run. My T3 and reverse T3, vitamin d and iron were all off. He changed me to natural thyroid. Waiting to see if it works. I started following a keto ( gluten and grain free too) diet. All healthy fats. My HDL was 135 last time. I got off of statins 2 months ago ( so many articles that say they are so bad) I went in and now my HDL is 65!!!! Lowest it has been in 9 years and that’s being off statin and just eating keto diet! And I’m losing weight! I also workout 4-5 times a week and was NOT losing weight until I switched to keto.

    • when a doctor will only prescribe synthroid you need a better doctor. i was that way until i got a ph by chance in the office and told her i want to try armour. it changed my life. i was normal again..

    • Has anyone ever checked your serum
      Copper and zinc levels as well as ceruplasim, the transporter of copper? Also when the zinc to copper ratio is off then it’s even more problematic.
      Your symptoms sound very indicative of low zinc and copper toxicity which can definitely occur easily after pregnancies and literally wrecks havoc on one’s health! Go to http://www.mensahmedical.com or direct healthcare access labs and get tested. Dr Mensah can provide a consult and a nutritional balancing plan. Quite possibly you still need a thyroid med but if your copper/ zinc levels are off and no one corrects it your problems will continue to worsen. I have seen countless similar situations and when PROPERLY treated its life changing. And definitely blood testingnrather then a hair analysis for copper is more accurate for both serum copper and “free” copper – the Cu in organs that builds up bc the binding proteins are too low to do their job properly of transporting copper.
      Good luck!

  3. I’ve had quite a rocky road to get to where I am today which is really NONE THE WISER.
    I have a TBI and right frontal lobe damage; I add this because I have no idea as to if this may be a factor, considering that it was my TBI which was complicated severely from my second and final pregnancy.
    After years of doctors calling me a liar and making stuff up for attention I was vindicated and thought that was going to be the point of getting back on the road to feeling good again.
    After fighting for well over a year with my primary doctor she ran hormonal tests (threatening me however with filing bankruptcy because she was hiding them unnecessary and when they came back normal the insurance wouldn’t pay and considering how costly they are and how many she was ordering upon my request it would be a lot) I was told I’d get a call or a letter in 7 days or so with the normal results as she knew they would be.
    They weren’t…
    My immediate Endo appointment was disheartening as the very first sentence from his mouth was “Sandra, what in the hell took you so long to make an appointment, surly you knew something was wrong well before now.
    Yes, I had a nodule removed from my left thyroid and have one in my right they monitor and at first everything went to normal after the surgery and Synthroid. It didn’t last long and my Synthroid was up and down but my symptoms were always there and my recent labs came back with a positive ANA and in awaiting a Rheumatologist referral however the last 5-6 years I’ve been existing. Existing in misery.
    I am always tired, exhausted, easily winded, my hair falls out, my body swells, my eyes literally hurt, I have constant headaches, increased balance and coordination issues, my weight I cannot control, I have digestive issues and I fear eating as it causes so many problems. I often times look 6 months pregnant.
    I am living a horrible rerun and I am desperate for advice.
    I know that my TSH levels are normal levels but they have been this way before when I was having Thyroid issues and the doctors didn’t know what to do and didn’t do anything and my question is maybe my brain injury has effected the way my body really IS by way of evaluating tests results?
    I’m not quite sure how to explain it but basically could there be merit to my idea or if there is any advice I’d welcome it with open arms.
    I am having a timewith my weight and it’s not from over eating or bad eating, I eat to live not live to eat and when I say that I could starve myself and not lose weight and actually gain I’m not exaggerating.
    My only weight loss I have is when my digestion and GI issues actually work and I no longer have a rock solid 6 month looking stomach.
    Gracious I have enough health issues and weight is something we are supposed to be able to control and manage which I’ve always done and until I had the thyroid symptoms my doctor ignored until my blood work I (not proud of it and using only as an example of my ability to control my weight) actually suffered from anorexia/bulemia which took years to overcome but was complicated mentally by myself because it was concurrent with my thyroid diagnosis.
    When my issues first started and I first started Synthroid along with intense counseling and therapy I was content at being between 135-150.
    I range from 175-190 now and there is no control I can have but I need it because it’s getting severe and will cause only more issues.
    Somehow I have a feeling I’m not alone in my position and there may be no way to get better.

    • OMG you just described me, only I have degenerative disc disease and permanent nerve damage. I became anorexic in high school from depression and suffered with it for years not because I thought I was overweight but because I had zero appetite. The thought of eating made me sick and if felt like my throats would swell shut if I tried to eat. I weighed 79lbs when I got pregnant at 20. After my children were born I had a lot of episodes of seizures like no pulse no heartbeat husband trying to revive me etc at 29 I was diagnosed with the degerative disc disease they wouldn’t do anything for it said I was to young at 39 they gave me fusion surgery and because my nerves were so damaged i didn’t even fuse they said I waited to long. In that time period my body changed like a light switch came on I weighed a healthy 125 had hair down to my butt full shiny I had super soft skin and over night it seemed like I gained weight hair thinned badly and skin became dull and dry I felt sick and tired bloated my eyes hurt and were blurry all the time. My doc said same stuff only it was blamed on my chronic pain test after test nothing but I wouldn’t give up moved to a diff state found a new doctor and first test I had 1553 antibodies discovered. Finally an answer so now it’s been months of medicine ups and downs. I am 45 started to see him I was 230lbs of bloat hard as a rock stomache also looked pregnant body ached like I was hit by a car hated to even look at myself cause I didn’t even recognize that person looking back at me and 9 months later I weigh 170 hair has started to grow back skin looks great again but I just can’t seem to keep it going like every time I make progress I have to up or lower my meds and it makes me feel weird I will start to feel bloated my hair feels thinner more in the comb etc I can’t seem to get past 170 and I would be happy with 140 because I’m not very tall 5’3 I have always felt like my DDD had everything to do with my thyroid changing. I actually have hashimoto cause my T3T4 are normal. I just want to be me again so badly. So you are not alone out there with no answers. I just hate living this way it’s not much of a life feeling this way. But I have to say that when the synthroid is working I feel amazing

    • You are speaking my language and I too am being ignored by SPECIALIST like endocrinologist Docs who should know better. It’s so disheartening to know that people like us stay chronically ill, suffer emotionally due to lack of validation, and this just makes us more sick and susceptible to additional autoimmune diseases! I have Hashimotos, Celiac Sprue, Arthritis, Migraines, CFS, Fibromyalgia etc.
      I have an elevated TSH level that will not come down despite taking levothyroxine, low free T4, and no one will believe my research/belief that my adrenals or cortisol levels are to blame. And the ONLY way to fix the thyroid issue is to fix the adrenals FIRST. I’m suggesting that you keep in mind that autoimmune diseases usually come in 2’s or 3’s etc. research which ones tend to cluster together (risk factors). For example I got Hashimotos Thyroiditis 1st, Can’t convert T4 to T3, Chronic Fatigue Syndrome soon followed (crazy making by itself) and also Fibromyalgia, Then 15 years later I got Celiac Sprue along with arthritis. I found out through research that Hashimotos, CFS & Fibro. , Rheumatoid Arthritis, Celiac Sprue, and Lupus commonly cluster together.
      I would also encourage you to research adrenals, cortisol levels, Addisons, Cushings, T4 to T3 conversion, leaky gut syndrome, etc.
      Doctors are becoming so lazy, arrogant, expect text book symptoms, deny our suffering and blame shift, leaving us more sick, depressed, and we’re forced to research it ourselves. I diagnosed myself with the Celiac due to being ignored, starved, told its in my head! I diagnosed my anemia by googling causes of excessive ice eating, I diagnosed my daughter with Hashimotos and my son with Celiac Sprue and yet I received no apologies proving them wrong and they take credit for the diagnosis! I’m fed up and hope at his helps you or anyone. It’s just so wrong.

      • Dawn I’m so sorry for your struggle to just get help! I had ITP as a child, had spleen removed and that was that. Nobody knew back then but that was auto immune I’ve been sick often on my whole life and also had anemia. I believe I was in hyper as a child and as I got older moved into hypo . My daughter was always sick as a child I took her to a gastroenterologist as well as allergist and nothing I did get a diagnosis that she was sensitive to wheat as a young child but nothing was explained to me I didn’t know that this was really gluten by the time she got To college by her sophomore year her hair was falling out she couldn’t concentrate she could barely see finally got her to somebody else and they diagnosed her with Hashimoto’s disease and celiac! I was diagnosed with how she Moto a couple years after her but I believe I had it for a long time . We were both on armor because it has the T4 in the T3 she’s more severe than I am and her doctor just put her on Tirasent and cytomel, I’m on WP thyroid, you have to be careful especially with your celiac, many drugs over-the-counter and prescription is like Synthroid I don’t know about the leva thyroxine though but I know I can’t take it have gluten in it or other fillers that affect our immune system even over-the-counter Advil has gluten in it my daughter suffers from migraines as well and takes Fioricet and once in a while has shots of Botox in her temples and around the top of her head she doesn’t like it but it did at one point keep them away for a whole year she had them every three months now she still gets them periodically but she’s also 100% Paleo and that helps a lot the foods we eat can be horrific to our systems . Have you read the book stop the thyroid madness and root cause ? Excellent books that really help it is written by Izabella Wentz, PharmD, FASCP
        And I agree I’m the one that found that I thought my daughter had the Hashimoto’s disease doing research from all her symptoms so I totally get it same with the silly yak it’s so frustrating !

  4. I was diagnosed with hyper/graves
    10plus years ago
    Other then the prescribed meds are there any natural organic meds that can be used if you kill your thyroid with the radiation pill.
    Reason for asking my hair is thinning out and I can’t lose weight but I workout everyday but I’m not gaining weight either because of me working out

  5. I’ve been diagnosed with hashimotos. the Dr has been upping my dose of thyroid meds for over a year. I’m taking synthetic 125 mcg. I am still gaining weight (50lbs. And counting!) I am getting so frustrated with trying to find what’s going to work for me. I have the feeling I’m going to be referred to an endocrinologist soon. I have to wait till the next time blood work is done to hear everything is good, then I have to make an appointment to see the dr to tell him I still feel exhausted and the weight won’t stop going up. I didn’t know about gluten being in synthroid! I was on levothyroxine prior to the synthroid. I’ve had the adrenals checked, and the Dr said they were OK.. this is taking so long to get this figured out! Wish me luck!! ?

    • i had same problem try t3 only for a while active form of throid. you will need 2 weeks for the t4 to clear then start t3 only for a while . go to Ben Greenfield podcasts they have a thyroid specialist that has gone this protocol for 3 years and is working well for her Good luck.