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6 Factors Which Can Affect The Conversion of T4 to T3

For those people who have normal T4 levels, but low or depressed T3 levels, a thyroid hormone conversion problem needs to be suspected.  The thyroid gland mostly produces thyroxine, which is also known as T4.  The thyroid gland also produces a small amount of triiodothyronine, which is T3.  Most of the T3 is produced by the conversion of T4 to T3.  But there are numerous factors which can affect the conversion of T4 to T3, which I’ll be discussing in this post.

Before I discuss some of the factors which can affect the conversion of T4 to T3, I’d like to briefly talk about this process.  The enzyme 5′ -deiodinase is responsible for this conversion process.  There are three forms of this enzyme, which include deodinase type I, deodinase type II, and deodinase type III.  The type 1 and type II deiodinases are primarily responsible for the conversion of T4 to T3, whereas the type III deiodinase is mainly involved in the inactivation of T4 and T3 (1) (2).  Most of this conversion takes place in the liver, although some of the conversion also takes place in the gastrointestinal tract.  As a result, if someone has liver problems and/or gut dysbiosis then this can potentially affect the conversion of T4 to T3.  A certain percentage of T4 is also converted into reverse T3, which I have spoken about in a different post entitled “Reverse T3: What You Need To Know About It“.

So why is it a concern if someone has problems converting T4 into T3?  Well, T3 is the active form of thyroid hormone.  Unfortunately not all endocrinologists test for T3, but when they do they will either test for total T3, where most of T3 is bound to a protein, or free T3, which isn’t bound to a protein.  Free T3 is what actually binds to the thyroid receptor.  If someone has normal T4 levels but low T3 levels then this is considered to be a hypothyroid condition.  Many medical doctors will only test the TSH and T4 levels, and the reason for this is because if the T3 is low then the TSH will typically be elevated, although this isn’t always the case.  I always recommend testing both the free T3 and free T4, along with the TSH.  If doing an initial thyroid panel it’s also a good idea to test the reverse T3, along with the thyroid antibodies.

Why Do Most Medical Doctors Give Synthetic T4?

When someone presents with hypothyroidism, most medical doctors will recommend a form of levothyroxine, which is synthetic T4.  A common brand is Synthroid, although there are other forms as well.  But if T3 is what actually binds to the receptor, wouldn’t it make sense to give the person T3 instead?  Well, some medical doctors will recommend synthetic T3 in the form of Cytomel.  However, many doctors are understandably cautious about doing this, as too high of a dosage can put the person into a hyperthyroid state.  Synthetic T4 will convert into T3, but of course if someone has a conversion problem then this won’t be the case.  Plus, even if someone doesn’t have a conversion problem they might do better taking a natural form of thyroid hormone such as Armour or Nature-Throid, which consists of both T4 and T3, along with T1, T2, and calcitonin.

Now that you have a better understanding of the importance of T3, I’d like to discuss the five factors which can have a negative effect on the conversion of T4 to T3.

Factor #1: Problems with the liver.  Since most of the conversion of T4 to T3 takes place in the liver, it would make sense that some health conditions affecting the liver can decrease the conversion of T4 to T3.  However, this isn’t always the case, as one study which investigated the relationships between thyroid function in obese adolescents with non-alcoholic fatty liver showed that they had a  higher conversion of T4 to T3 due to increased deiodinase activity as a compensatory mechanism for fat accumulation (3).  With that being said, if someone has problems converting T4 to T3 it usually is a good idea to give some liver support, such as milk thistle and N-acetylcysteine.

Factor # 2: Gut dysbiosis. As I mentioned earlier, the good bacteria in the gut helps to convert T4 into T3 through the help of an enzyme called intestinal sulfatase.  There isn’t much evidence in the literature showing that gut dysbiosis negatively affects the conversion of T4 to T3, but obviously if someone has dysbiosis then this should be addressed even if they aren’t having a conversion issue.  I did come across one study which showed that Crohn’s disease can affect the conversion of T4 to T3 (4).

Factor # 3: Selenium deficiency.  The iodothyronine deiodinases all contain selenium in the form of selenocysteine, and they play crucial roles in determining the circulating and intracellular levels of T3 (5).  Numerous studies show that a selenium deficiency can affect the conversion of T4 to T3 (6) (7) (8).  However, this might only be the case with a severe selenium deficiency, as one study showed that only when selenium levels were decreased by more than 80% was deiodinase activity markedly decreased (5).

Factor # 4: Stress.  Elevated cortisol levels can affect the conversion of T4 to T3.  Studies show that stress can inhibit both type I iodothyronine 5′-deiodinase activity (9), as well as type II 5′-deiodinase activity (10) (11).  This is yet another reason why it’s important to improve your stress handling skills.

Factor # 5: Certain medications.  Amiodarone is an anti-arrhythmic compound, and due to the structural similarity between this and thyroid hormone it apparently inhibits the activity of 5′-deiodinase (12).  Beta blockers are commonly taken in hyperthyroid conditions, and certain ones such as propranolol, alprenolol, atenolol, and metroprolol can affect the conversion of T4 to T3 (13).

Factor # 6: Pro-inflammatory cytokines.  There is also evidence that certain pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) can inhibit type 2 5′-deiodinase (5’D-I) enzyme activity (14) (15) (16).  These cytokines are commonly present in autoimmune conditions, including Hashimoto’s Thyroiditis and Graves’ Disease.

In summary, normal T4 levels along with low T3 levels frequently indicate a conversion problem.  This involves the enzyme 5′-deiodinase, and is one reason why when obtaining a thyroid panel you want to not only look at the TSH and free T4 levels, but also the free T3.  And it usually is a good idea to look at the reverse T3 as well.  Six common factors which affect the conversion of T4 to T3 include problems with the liver, gut dysbiosis, a selenium deficiency, high cortisol levels, certain medications, and pro-inflammatory cytokines.


 

23 Comments

  1. Linda says:

    1) can too much selenium, too little cortisol, too much RT3 also reduce T4 -> T3 conversion?

    2) since milk thistle increases the rate drugs are cleared through the liver, should it be avoided if taking thyroid prescriptions? does the same hold true for NAC?

    3) especially for those having MTHFR defects, any valid tests to accurately measure the amount of each of these: deodinase type I, deodinase type II, and deodinase type III? how can one increase deodinase type I and deodinase type II AND/OR decrease Type III?

    thank you

    • Dr. Eric says:

      Hi Linda,

      I don’t think that too much selenium will reduce T4 to T3 conversion, although I’m not 100% certain of this. You do want to be careful about taking high doses of selenium, as it can be toxic. High RT3 can decrease the conversion, but depressed cortisol levels shouldn’t decrease the conversion. I commonly give milk thistle and other herbs/nutrients which increase glutathione (i.e. NAC) to patients who are taking thyroid medication, and it doesn’t seem to decrease the effectiveness. Unfortunately I’m not familiar with any labs which allow you to test the different types of deiodinase enzymes.

  2. Gina campanella says:

    My tsh is very low as is my t3 with low to normal t4. Would you suggest i have my doctor test for the above factors (i.e low selenium etc.) Prior to supplementing on my own? Would the above factors still apply when you have very low t3 as well as very low tsh?

    • Dr. Eric says:

      Hi Gina,

      Are you taking synthetic thyroid hormone? If so then this can depress the TSH and the thyroid hormone levels can still show up as being low. If you aren’t taking any thyroid hormone medication yet have a low TSH and low thyroid hormone levels then this can be caused by low levels of serotonin or dopamine, or can also be due to elevated cytokines, prolactin, or cortisol.

  3. Jamie Smallwood says:

    Thank you for this article. I was diagnosed with Graves Hyperthyroidism. I have suppressed TSH at less than .01, normal range for T4, and my T3 was elevated. So does that mean I could have a conversion problem, but the other direction converting too much?

    • Dr. Eric says:

      Hi Jamie,

      It is possible that you are overconverting T4 into T3. Up-regulated 5′-deiodinase activity is usually caused by elevated testosterone levels. Thyroid hormone resistance can also cause high levels of T3 and normal T4 levels, but this usually is characterized by a normal or elevated TSH.

  4. Tess says:

    All I know I had graves. I remember my TPO so high like 1500 and now it is down to 200 and now people tell me I might be developing Hashimoto’s Thyroiditis.

    Your article was very helpful, and yes, I know I have fatty liver non Alcoholic and I changed my diet. It appears, I do not have graves for now or will I always have it. Anyway, I was tested for other immunes and clean and allergy clean except for dust mites, mold.

    I want to know I started taking colostrum and I also take B panel that has good folic acid with the MTH in front and same with B12. I take cod liver oil, Vitamin D, B6 100mg,and Selenium.

    How can I deceased my deodinase, or increase if I have too. What are cytokines or not make them inflamed. How can I correct them and I know diet is something that I am always working on and especially, our foods of today; which is also another subject and many issues that can be subject to thyroid.

  5. britt says:

    Do you have any articles that address lower t4 and low to normal t3?

    • Dr. Eric says:

      Hi Brittany,

      Low T4 and/or low T3 are common with hypothyroid conditions, with Hashimoto’s Thyroiditis being the most common cause. While taking thyroid hormone medication might be necessary if both are low, addressing the cause of the problem is also important. I would recommend attending one of my free webinars on hypothyroidism and Hashimoto’s Thyroiditis for more information.

  6. Tanja says:

    When I was taking Euthyrox (similar to Synthroid) my TSH was low, fT4 was at the high end of range and fT3 was always at the low end of range. I was feeling lousy. Now I’m on NDT (Thyroid S) and the latest test showed very low TSH (expected), fT4 at the bottom of range and fT3 at the top of range, which is great. I feel quite good.
    So, should I worry about the low fT4 now, or this is ok?
    Thank You

    • Dr. Eric says:

      Hi Tanja,

      Since T3 is the active form of the hormone I’m more concerned when T3 is low. Plus, keep in mind that even if you are taking synthetic T4 it won’t increase T4 levels on the blood test, and so as long as the TSH and free T3 levels look good and you’re feeling good I wouldn’t be concerned about the low T4.

  7. VINOD says:

    SIR.

    MY TSH LEVEL RANGE IS 6.88 TO 7 FROM JULY 14 TO JAN.15 I TAKE REGULAR THYRONOM 100 MCG. FROM MARCH 15 TSH LEVEL IS 0.47 TO 0.03 NOW TODAY 24.04.15 TSH LEVEL IS 0.01 WHAT I DO

    REGARDS
    VINOD JOSHI
    9829035461

    • Dr. Eric says:

      Hi Vinod,

      The first thing I would do is get an updated thyroid panel to also look at the thyroid hormone levels, and also test the TSI antibodies for Graves’ Disease. It is possible that the dosage of thyroid hormone medication you’re taking is too high. On the other hand, if you have elevated thyroid hormone levels and elevated TSI antibodies then this indicates you have Graves’ Disease.

  8. Elaine says:

    I was diagnosed with Hypothyroidism almost 30 years ago and my Endocrinologist has told me that my thyroid gland is almost nonexistent. For this reason I am confused over treatment options when my only salvation is Synthroid. How can any natural product help my thyroid when it isn’t there? I need replacement therapy.
    I would appreciate your insight on this important topic.
    Thank-you.

    • Dr. Eric says:

      Hi Elaine,

      I agree that you probably need to take thyroid hormone medication, as there is no natural substitute for thyroid hormone. However, there are better alternatives to Synthroid, as Tirosint doesn’t have all the chemicals that Synthroid has, although it is more expensive. And there is the option of taking natural thyroid hormone medication such as Armour or Nature-Throid.

  9. Hodaya says:

    I have low t4 to t3 conversion after being fine on t4 for 20 yrs. I took slow release t3 and cynomel but tried ndt since I still feel exhaused. I have Hashimotos and take all the supplement from STTM website as well as your suggestions. My temp is variable low 36.2-36.7 (was 35). I take numerous adrenal supplements as well. Any more suggestions for Hashi? I got my Thyr Abs from 3000 to 900. I am on a candida, gaps, fod map ,low estrogen diet and take numerous immune booster supplements.

    • Dr. Eric says:

      Hi Hodaya,

      It sounds like you’re doing some great things for your health, as you are eating well, avoiding the common allergens, doing things to heal the gut and improve the health of the adrenals, etc. I of course would make sure you are blocking out time to manage stress, minimize exposure to toxins, etc. If you haven’t attended one of my free webinars on hypothyroidism/Hashimoto’s I definitely would recommend doing so, as I go into greater detail about some of the things people with this condition need to do in order to greatly improve their health.

  10. Carol Burmeister Prichard says:

    I was diagnosed with Hoshimoto’s and hypothyroidism in 2003 & I continue to get more symptoms & they have progressively become worse. (Had systemic candida from 1982-1995 when a live cell blood analysis showed tropical parasites in my blood which I believe was my trigger.) Changed from Armour Thyroid to NaturThroid 65mg 8/14. New Doctor (functional medicine) increased dosage to 97.5 mg in Oct. with labs that were fine. After labs 3/15 with TSH 0.10, Free T4 0.9, FreeT3 2.4, T3 Total 76, this new doctor increased the dosage again to 146.25. She also had me taking iodine since Oct. Fatigue even worse – have to nap every day. Very low energy level – have lost muscle. Hands not shaking but on the edge. Heart palpitations on couple of occasions. Heartburn back after getting rid of it several years ago but also feel strange sensations in neck area. Labs 5/15 TSH 0.03, Free T4 1.3, Free T3 2.3, T3 Total 56,TPO 14 reference range of <9 IU/ml . I have been doing a gut cleanse since 4/1/15. Lots of constipation, belching, gas, bloating. I am dairy, gluten, corn, soy, and sugar free. When stopped dairy in 2010 lost 12 lbs. Stopped gluten 2012 lost 3more lbs. Then started losing weight for no reason but previous Doctor & new Doctor not concerned. Now down to 103 lbs.& can see my rib cage and hip bones. Friends are concerned and so am I. Doctor feels I'm obsessing. I also feel I am hyperthyroid and may have adrenal issues. After changing her mind 4 times at my visit last week I am now taking 65 mg. NaturThroid. I think further testing needs to be done and I need to get to the bottom of the weight loss. Is it possible I have both hoshimotos and graves?

    • Dr. Eric says:

      Hi Carol,

      It sounds like you’re doing a lot of good things for your health, but based on what you mentioned in your post it might be time to look for a different doctor. It is possible to have the antibodies for both Hashimoto’s Thyroiditis and Graves’ Disease, although taking a higher dosage of thyroid hormone than is necessary can cause hyperthyroid symptoms (including weight loss). And of course there can be other reasons for the weight loss, and since your current doctor isn’t addressing any of your concerns it makes sense to get another opinion.

    • Cathy says:

      Having the same symptoms as you. I’m losing lots of weight. I also have Candia and other bacterial infections. I started looking at dr Jennifer Daniels videos and have started the turpentine protocol. It seems to be working fine. I’m keeping my fingers crossed.

  11. Adan says:

    The confusing part for me is you discuss a conversion problem of T4 to T3, but the proper test is FT4 and FT3. Should we be reading T4 and FT4 interchangeably in this article? If my labs show normal FT4 and low FT3, does that mean a conversion problem, even though I don’t know T4 and T3 levels? Thank you doctor.

  12. Teresa says:

    Hi I am on Synthroid and cytomel but the cytomel makes me irritable and I have more hot flashes/ night sweats, blood pressure goes up, fluid retention, weight gain etc. I know you are supposed to add T3 meds with your T4 but it makes me feel worse ?

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Natural Treatment Methods:
Graves Disease Treatment
Hypothyroidism Treatment
Hyperthyroidism Treatment
Natural Thyroid treatment


Conventional Treatment
Methods:
Radioactive Iodine
Thyroid Hormone