Informational Posts

Many Thyroid Patients Aren’t Converting Their Medication

Originally published on 5th June 2016
Last updated on 2nd February 2024

Many thyroid patients are on thyroid hormone replacement medication, such as Levothyroxine or Synthroid and still feel unwell. It may be due to a lack of conversion from T4 to T3.

Frustrated With Thyroid Doctor

What Do Thyroid Hormones DO?

A healthy thyroid gland produces five hormones: T1, T2, T3, T4 and Calcitonin. (although T1 and T2 are possibly made outside the thyroid gland, though this isn’t important for this article!)

Thyroid hormones are needed for every process and cell in your body, especially T3.

Although we have more T4 than T3, T3 is the most active.

T4 is about 90% of what the thyroid gland produces, with around 9% being T3 and adequate levels of both are needed to help us feel well and carry out all our usual bodily functions and processes.

When we are on T4-only medications such as Levothyroxine or Synthroid, T4 must convert to T3 to create the T3 we need to correct the hypothyroidism and feel well.

The main purpose of thyroid hormone, produced by the thyroid gland, is to ensure the metabolism is running properly. You might think that the metabolism’s job is just to burn calories, but it is also to produce heat and fuel to keep us warm and give us energy.

However, if we don’t have enough thyroid hormone (T4 and T3) , we can have a slow metabolism, with symptoms such as cold intolerance (from the lack of heat made) and extreme tiredness and weight gain (from the lack of calories burned to make energy), among lots of other symptoms of hypothyroidism.

T4 to T3 Conversion

An inability to properly convert T4 to T3 is common among thyroid patients and can even result in a fluctuating TSH, or a TSH that is ‘in range’ and a low Free T3.

Many patients have an in-range TSH, but when they check their Free T3 and Free T4 levels, they see that the T4 from their thyroid medication is not converting to adequate levels of T3. 

This can be caused by an enzyme called iodothyronine deiodinase, that is deficient for some people, as they have the Deiodinase 2 (DIO2) gene variant.

The DIO2 gene was researched in 2009 and the results were published in a paper titled “Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine plus Triiodothyronine Therapy in Hypothyroid Patients.”

The DIO2 gene activates the active thyroid hormone T3. The researchers found that a small change in this gene could mean that thyroid patients have ongoing symptoms on T4-only medicines such as Levothyroxine.

Patients in this study were given levothyroxine (synthetic T4) only for a set period and then combination treatment of both levothyroxine and liothyronine (synthetic T3).

The patients who had normal genes did not feel any different on the combination treatment, but those who had the DIO2 gene felt better on combination treatment.

The enzyme iodothyronine deiodinase is important in the activation and deactivation of thyroid hormones, as T4 is converted into T3 by deiodinase activity.  A problem with this can therefore cause conversion issues, where TSH may look ‘fine’, as well as the Free T4 level, but with a low Free T3 and continued hypothyroid symptoms and development of other health conditions (such as mental health and heart/blood pressure problems). Low or deficient levels of trace minerals selenium and zinc can also cause conversion issues.

The BBC show ‘Trust Me I’m a Doctor’ even covered this issue:

Sometimes when patients are diagnosed with hypothyroidism and prescribed T4, this doesn’t make them feel any better. It may be that these patients have trouble converting T4 into the active version of the hormone, T3. This process is dependent on enzymes in the body that need certain nutrients to function. It could be that these enzymes are not working properly, or the body isn’t producing enough of them or it could be that patients are lacking the nutrients needed for these processes, such as selenium. An alternative treatment option is to take T3 – the active hormone.

Rachel Struggling With Mental Health Thyroid

Poor gut health may also contribute to poor T4 to T3 conversion.

The gut assists in converting inactive thyroid hormone T4 to active T3 (which is what we need for energy and many functions within the body), which requires an enzyme called intestinal sulfatase.

However, this enzyme comes from healthy gut bacteria. An unhealthy gut can lead to a lack of this important enzyme.

Intestinal dysbiosis is an imbalance between pathogenic and beneficial bacteria in the gut, which can significantly reduce thyroid hormone conversion – just one reason why people with poor gut health may have thyroid symptoms but ‘normal’ TSH test results

Symptoms of Poor T4 to T3 Conversion

Conversion problems and issues with thyroid medication properly working may be caused or influenced by adrenal dysfunction or vitamin deficiencies such as iron, zinc or selenium. Poor gut health can also be a contributor. [1]

By addressing these, you may fix or improve the conversion issue, but many other people simply have a problem converting T4 to T3 and don’t know why.

However, troubles converting thyroid hormone are a big reason as to why T3 and NDT medications can work better for a lot of thyroid patients. As opposed to T4-only medications like Levothyroxine or Synthroid, NDT or synthetic T3 medications give direct T3, so the patient doesn’t have to rely on their body to convert it.

My Switch From Levothyroxine to NDT

I was unwell on Levothyroxine and only felt worse as time went on but have reclaimed my health and life by switching to NDT medication which contains direct T3. 

If you’ve tried raising your dosage of T4-only medication and feel even worse, then this could be a sign of a conversion problem, as you may not need any more T4, but instead T3.

If your doctor runs thyroid test after thyroid test and says you’re still ‘fine’, even though you feel rubbish, then it could indeed be a conversion problem. If they only test TSH and Free T4, then this would not show up a conversion problem. A low Free T3 would show insufficient amounts of T3 in the blood.

Conversion issues are a big reason why I support the option of Natural Desiccated Thyroid and T3 medication, especially when we see how incompatible T4-only medication can be for some people.

The only way to know for sure if conversion issues are holding your health back is with thorough and full thyroid testing. If your doctor won’t order the full thyroid panel (including the all-important Free T3), then you can do so quite inexpensively online. Medichecks cover the UK and LetsGetChecked cover most countries worldwide.

Related Article: Signs Your Thyroid Medication May Need Adjusting

What Does a Conversion Problem Do?

Not being able to adequately convert T4 in to T3 can leave you hypothyroid and not optimally medicated. Your hypothyroidism isn’t optimally managed, meaning you may still have a lot of symptoms, and mental health also often suffers.

Having low Free T3 can be the cause behind depression, mood swings, anxiety etc. when on t4-only medication. This was certainly true for me. When I switched from T4-only Levothyroxine to NDT,  my anxiety, depression and over-emotional tendencies lifted quickly.

T3 has an important role in the health and optimal functioning of your brain, including: your cognitive function, ability to concentrate, mood, memory and attention span and emotions and ability to cope with life’s stresses. T3 interacts with brain receptors and makes the brain more sensitive to chemicals such as Serotonin and Norepinephrine, which affects your alertness, memory, mood and emotion.

Have you been checked for conversion issues? Let me know in the comments below. 

See also:Book1Edition2CoverWithShadow

The book Be Your Own Thyroid Advocate: When You’re Sick and Tired of Being Sick and Tiredwhich contains helpful information like this article and so much more.

You can click on the hyperlinks in the above post to learn more and see references to information given.



About Author

Rachel Hill is the highly ranked and multi-award winning thyroid patient advocate, writer, speaker and author behind The Invisible Hypothyroidism. Her thyroid advocacy work includes writing articles, authoring books, producing her Thyroid Family email newsletters and speaking on podcasts and at events about the many aspects thyroid disease affects and how to overcome these. She is well-recognised as a crucial and influential contributor to the thyroid community and has a large social media presence. Her bestselling books include "Be Your Own Thyroid Advocate" and "You, Me and Hypothyroidism".


  • Breege
    September 2, 2023 at 7:23 pm

    Had a genetic test and found out that my DIO 1&2 SNPs mean that my conversion of T4 to T 3 is moderate. Been symptomatic for 12 yrs now. Experimenting with T3 doses but realised that I need a little T4 added on. Something is very wrong with my HPA and I’m working on improving that so that my meds can work well. Right now I’m close to being bed bound on sleep days but if I eat all day abs now allow myself to get hungry I can function. It’s no way to live. I eat more than my husband but we eat healthy; no gluten, sugar, processed food, oils, only whole food so no weight issues. Hoping to get to the bottom of this by the end of this year. I need my full life back 🙏🏻

  • Anne
    November 2, 2022 at 10:03 pm

    Three years ago I had both thyroids removed within five weeks as my right one was cancerous. Since that time I have had an uphill battle with doctors and my Endocrinologist. No one is listening to me when I tell them that I am tired all the time, have gained over a stone in weight despite watching what I eat , very anxious all the time and often weepy which is embarrassing, aching legs. I asked my Endocrinologist whom I have had 2 telephone consultation s with her and one face to face in September would she give me a small amount of T3 to try for three months to take with my 100 micros of Levothyroxine but she said that it could affect my levels (whatever that means) and I could have a stroke of heart attack. She just raised my Levothyroxine by 25 micros on alternative days and said I would have a blood test at a later date. I asked about NDT and she flatly refused. I told her that the Levothyroxine did not suit me but they think that ‘one size fits all’ and it certainly doesn’t suit me! she said that she would see me again in six months time. At the end of my appointment she said ‘ If you want to see an Endocrinologist privately then, feel free! That to me speaks volumes! I would like to try NDT and a small amount of T3 but I wouldn’t know how to go about it apart from going privately. suggestions please?

  • Christina
    November 25, 2021 at 3:39 am

    Good article. I am facing many of these issues as well..

  • Brian Porter
    July 15, 2021 at 9:26 pm

    Our son is very sick in the hospital. He has catatonia and is not responding to antipsychotic treatments. He has extreme anxiety and hypothyroid symptoms, cold intolerance, constipation, more. His TSH fluctuates between 2 and 4. He has been on synthroid but this does not change his TSH level.

    I have DNA tested him and his #1 problem noted is magnitude 3, ‘significantly reduced T4 to T3 conversion’ brain effects. rs2235544(A;

    His #2 problem noted is rs180223(G;T) 1.3x to 11.5x increased risk of autoimmune thyroid disease.

    Any ideas what could help our son?
    Brian Porter
    [email protected]

  • Kris Murphy
    February 2, 2021 at 2:11 am

    Thanks for the information. I am a poor converter of T4 into T3. I have been on Armour Thyroid (T4 & T3 combination) and have responded well. Now my doctor refuses to refill my prescription and wants to switch me back to T4 only medication. Is it possible I can also take the idonodase enzymes? Where can I obtain them? Pharmacy?

    • Barbara Belland
      May 4, 2022 at 1:50 pm

      I had to quit a fantastic high paying job because i was dying and could not find help. What I did over 12 yrs ago is call a dr office and just ask does this dr prescribe Armour Thyroid? If they said “no” I hung up. Kept doing this until I found some. Now alot of drs prescribe it but do not know what they are doing. This is very frightening and people are going bald and VERY sick everywhere. Drs need to stop being so closed minded. Best wishes and do not give up.

  • Jo
    January 28, 2021 at 8:50 am

    Thanks for this. I have a GP appointment today, hoping to make sure progress. I had my levo dose reduced because I was getting some hyper symptoms and my T4 was above range. They tested again 6 weeks later and my T4 is still above range but my TSH has also jumped up to 2.7 and I am feeling *awful* – fatigue, headaches, cold… Wondering if this could be a conversation issue. Hoping they’ll take it seriously.

  • AnnieB
    October 3, 2020 at 8:57 pm

    I’m having a difficult time understanding doctors who don’t believe in T3. T3 is THE active thyroid hormone. What makes doctors not believe that it’s important for metabolic function? Why would anyone who deals with thyroid patients discount important considerations regarding their health?

  • Cynthia Anderson
    December 27, 2019 at 11:23 pm

    Relationship of Central Hypothyroidism to Cold War above ground Nuclear testing—–I had always tested normal TSH and low normal fT3 and fT4, but felt awful. I suspected central hypothyroidism due to my symptoms and to exposure to ionizing radiation during the nuclear testing in the 1950’s which left radioactive fallout scattered across the US—not just near the test sites. My endo would not treat me until nodules were discovered on my thyroid, but then with only the tinisest amount of levothyroxine (based on a “normal” TSH), which still left me feeling like I had hypo symptoms. I finally got my primary care to listen to me and do some research on his own, after which he upped the levo dosage, which helped, but fT3 and fT4 never made it out of the lower third of the range. So he suspected I also was not converting T4 to T3, and added in liothyronine. That helped! In the meantime after years of not adequately treating me, my endo reluctantly ordered a pituitary scan which showed a 4cm meningioma (most common cause being inonizing radiation) in the left lateral ventricle of my brain. I had minimally invasive surgery done on it due to the location being difficult, so the mass is still there, but asymptomatic aside from pressure it may exert on the hypothalamus/pituitary.
    When I am feeling correctly dosed, my TSH is nearly 0, and fT3 and fT4 are in 3rd quartile. I find a low dosage of T4 with a higher T3 dosage works best for me. But, I also find that getting the right tests ordered for checking levels is difficult. They always want to do TSH which is useless for me overall, and are very reluctant to test fT3, even though I am on primarily T3 therapy. I assume this is an insurance issue.

    So, just want to say that I suspect our history of nuclear testing has left marks on the health of a lot of people who don’t even realize their problems are from exposure to ionizing radiation as infants. The endocrine system was particularly vulnerable, especially the thyroid. The National Cancer Institute has a dosage calculator for those born prior to 1982 that will take into account your birth location by county, date, and estimated amount of milk consumed (the radioactive iodine ended up in dairy products). I find it interesting that I ended up with 2 things—the large meningioma and the thyroid/endocrine issues—that are linked to radiation exposure. Sadly, most medical professionals are not aware of those links, so I believe a number of people in my age group—those born in the 1940’s through 1960’s have conditions that are being overlooked or not taken seriously. Additionally, there is the possibility that mutations due to radiation exposure have been passed on to our children. I think central hypothyroidism is probably much more common than realized–though next to impossible to get treated unless you essentially become your own doctor. Good luck to all!

    • BarbyJean
      May 4, 2022 at 2:05 pm

      In grade school (around 1959) they gave us chocolate flavored iodine pills everyday! Now I can see why the influx of thyroid problems today. 12 yrs ago I was dying with T4, my GP dr then would not test my thyroid—I finally talked him into it and it was VERY high TSH 15. I fired him and kept calling around until I found a dr who would prescribe Armour Thyroid (could not use any other NT meds). Before this I would come home from work eat a sandwich and go to bed and my heart was racing all the time with really bad fatigue. This is a worldwide problem and drs are clueless and very closed minded. Now they raised the price of Armour sky high. There is a way to get it free look up “AbbvieAssist” online. There is a form to fill out with dr signature and if you make under $109,000 per year you may qualify for free Armour Thyroid. I am going to ask my dr to help me with this and see. Best Wishes, never give up!

  • Lia
    October 15, 2019 at 4:54 pm

    Thank you for your post. Guess I have this problem of conversion. I’m taking Synthroid, but only because in my country we don’t have access to other types of medications (suca as NDT or T3). Does anyone have some piece of advice for me to address this conversion problem with T4-only medications? I would really appreciate it!

  • Lauren
    September 20, 2019 at 9:54 am

    i’ve been researching this and think it is my problem too. In Uk our drs wont do the T# test, I have asked for it to no avail. I can’t afforf to get myself tested let alone buy my own medication. also, on behalf of people already taking T3 on prescription elsewhere I’m sorry to hear the news of it stopping been prescribed for many because of the cost. This seems so unfair and will leave many with worse symptoms. The fight against obesity is already a major struggle and costs the NHS millions we are told, so why increase the likelihood by undertreating hypothyroidism, it makes my blood bol, We get told to follow a healthy lifestyle, well I for one have been since i was 18, I’m 51 now and post menopausal and have more problems than ever. Drs suggest most of these are down to the thyroid and say keep taking the medication, which I do but i feel worse I’ve been on it for 5 years now and the side effects far outweigh my initial health complaint of tired all the time. I was keen to take levothyroxine at first, thinking i would lose weight which was slowly creeping up despite healthy living. However it is zooming up in the last couple of years and my vitamin D levels are low before the vit d supplements being prescribed my vit D level was near zero and i kept having falls.
    I’m coping with depression due to my health since been on levothyroxine yet if i stop taking it within a few weeks im in A and E.

  • Debbie Braun
    August 30, 2019 at 6:30 am

    I’ve been on t4 and t3 now for about 3-years now. I do the compound t3 and take my t4 with it about 3xs per day. I will be on this for life a gene I got from my father! I could never lose a pound was constantly hungry always tired. Not one diet worked. I do better on the compounding t3 stays in my body a lot longer verses prescribed t3 out of my body fast.

  • Lulu
    August 1, 2019 at 12:22 pm

    Hi Rachel☺️. Thanks for this post. It’s interesting that you mention that if a person is only tested for TSH and free t4, then a conversion problem will not show up. That are the sole two tests that I am given. When I mentioned having anything else tested, my endo nurse said it wasn’t worth testing t3 as my free t4 was in range. I have an appointment with my GP in a couple of weeks- I think I should mention it to them.

    Thanks again

  • Sarah
    March 29, 2019 at 4:11 pm

    Thank you! I thought I was going mad until I read this. I have an underactive thyroid, I was diagnosed just over a year ago when my TSH was so high that it was off the scale(over 100). I’ve been on T4 for just over a year and feel no better whatsoever, now my T4 is borderline high and so is my TSH which i think means that my body is still lacking T3. The endocrinologist I have seen recently doesn’t ‘believe in’ T3 and has increased my T4 dose. I feel worse on the higher dose just like you have said!! I have some link to buy some T3 from abroad, but I a not brave enough to do this without a professional telling me how much to take and testing my bloods! Or maybe i’ll just do it, it seems that Doctors (both NHS and i’ve tried paying privately) aren’t capable of treating me so I might just have to take the plunge!

  • Susie
    December 18, 2018 at 8:45 am

    Hello! Someone in my Facebook group shared this website with us so I came to look it over. I’m definitely enjoying the information.


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