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What amount of T3 are people on who have the DIO2 type II DIO2 (T92A) rs225014 Heterozygous variant genotypeTA any info will be interesting

Deiodinase lodothyronine type II

DIO2 (T92A) rs225014

Heterozygous variant genotype TA

I think this means i have inherited from one parent but got 2 defective genes thats about all i was told by counsellor she really wasnt very clear on explaining it all,,, I am told to add T3 to levothyroxine to feel better, I had just been to an Endo before i received this test, he had reduced my Levothyroxine from 150mg to 100 and added 20mgs of Liothyronine T3 which is to be split into 2 doses taken am & pm... does anyone know if this is the right dose for this gene or should i have more added,

I do feel better on this mix but I think i have more room for improvement , my head is much clearer and energy level as better and have been told I have colour in my face and i no longer look like im dead as I now gave a glow in my cheeks, i no longer look totally stressed and dont look or act like I'm about to kill someone anymore,, omg I didnt realise thats how i had looked to others funny how people only mention these things when you look better, I

I still have a few muscular pains going on, I have only been on T3 for 6 days,, so hopefully other things will also improve soon just wondered what others with this defective gene what they have been prescribed , is 20mgs enough or should i be asking to get more to reach the muscular pain ? and to help my hair grow back thicker as I have been Hypo 12 years now and suppose all the pains and everything I have been feeling will not go away over night..

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The thyroid secretes about 6 mcg of T3 per day. So, allowing for some variations in your levels from taking tablets instead of steady secretion 10 mcg L-T3 would be plenty. (It's possible a little more would be required as there is evidence the thyroid plays a role in peripheral T4 to T3 conversion - this would apply to all patients, not just those with the DIO2 polymorphism).

The original research found minor improvements in patients with the CC genotype as opposed to TT genotype. There was a lesser response for patients with the heterozygous TC genotype. The research is here academic.oup.com/jcem/artic... .

Two points : -

1. This polymorphism only has minor effects, most patients who need T3 medication have substantial symptoms that resolve when they take T3, often at doses well above that needed to compensate for the polymorphism.

2. The research compares CC with TT genotype. The company that sells this test reeports TA genotype! I've no idea where this comes from, I tried asking the company but they did not respond. It doesn't make sense. Who knows what they are testing and reporting. I would ask them for a detailed explanation or your money back.

The rs225014 is pretty irrelevant. The test can be useful to hookwink a reluctant doctor into prescribing liothyronine but the minor impairments from the polymorphism don't match up to the substantial signs and symptoms patients have. Your endo is prescibing L-T3 at a reasonable dose which seems to be working. I would give it a few months as some more symptoms may resolve.

About 40% of the population are heterozygous for this polymorphism and although there are some links with other disorders (e.g. insulin resistance) it doesn't seem to affect their thyroid status until they become hypothyroid. We can find all sorts of genetic variations that affect our chances of getting this or that disorder, it's just normal variation, nothing to worry about. The effect of this polymorphism on type-2 deiodinase is so small no difference in serum T3 occurs between the groups with and without the polymorphism. Subjects with this polymorphism can convert T4 to T3 perfectly well, just not quite as well as others and so do not respond so well to levothyroxine only treatment.

As regards muscular pain good quality sleep makes a huge difference and your evening dose of L-T3 should help you get deeper sleep (which produces growth hormone which heals micro-damaged muscles / tendons). Also, try supplementing with magesium if you don't do so already.

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1. This polymorphism only has MINOR effects, most patients who need T3 medication have SUBSTANTIAL symptoms that resolve when they take T3, often at doses WELL ABOVE that needed to compensate for the polymorphism.

With due respect, your above quoted statement is contradictory, is it not ?

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Where's the contradiction? What I am saying is that the polymorphism has minor effects that only show up when patients become hypothyroid and are treated with levothyroxine only. Many patients, like yourself, have quite substantial or even severe symptoms which only resolve when they are given doses of T3 well above the 6 mcg that the thyroid produces. i.e. the polymorphism is irrelevant to these patients.

The polymorphism only matters in subjects who are homozygous and even then the effects are small and no difference in serum T3 levels can be detected. These patients can convert T4 to T3. They just have slightly impaired type-2 deiodinase, so slight you can't see the difference in blood T3 levels.

On top of this it's not even clear if the Regenerous test is measuring the correct gene, as noted in the other post Regenerous are reporting A and T bases when the research reports C and T bases. This may be correct, I find genetics too complex, but I can't get a response from Regenerous. Patients who receive advice from their 'experts' seem to get vague responses.

It doesn't matter whether or not you have this polymorphism, your symptoms and treatment are much the same. Those patients who believe they have the polymorphism may be wrong, we don't know what the Regenerous test is testing.


Thank you for replying; it makes more sense to me now.


I know nothing about genetics either!, but I find you " jimh111 " to be stating things that you are not 100% sure about and therefor maybe stopping people use Regenerus testing which could be used on you for Slander if they lose customers from your comments on them and this is not a true fact !,

I see that you have admitted in your posts you know nothing about genetics... I would like to add this genetic testing which came from Regenerus is recommended on the thyroid.uk web page and it is them who have recommended this testing for this faulty gene! So myself and others have not just randomly got it off the internet..

Maybe instead of writing to them I suggest you call them to find out and if they can tell you why they use T & A and not what you have read about on some reports you have found on the internet! and if they can not answer your questions ask them for the name number or address of someone who can ,

Can I point out that it is YOU who is doubting the genetic testing we have had done and you are the 1st Ive seen do this, So please could you find out and stop bandying it around this forum until you have found out the answer to this is a factual one as you are talking very strongly that you do not think this testing is the right one, I do not think you should be telling everyone to complain as it could cause havoc, but you 1 person calling should be able to get the answer as I said it is your doubt not other peoples !

I suggest you get your facts right on the genetics before putting off everyone who has had the test done or have put doubts for future people who want to use Regenerus for DIO2 genetic testing!


I've sent another request to Regenerus. It's no use telephoning them as the subject matter is too complicated and it would take a long time to get through to the right person. I will put any response on my original post.

Even if the test is checking for the correct polymorphism we should note that this polymorphism is associated with minor improvement with combined L-T4 / L-T3 treatment. Most patients who need T3 medication have substantial or severe symptoms that are not a consequence of this polymorphism.

And what about the majority of patients, who do not have this polymorphism, but clearly need T3? Are they supposed to be denied T3 treatment just because they 'failed' a genetic test?


Jimh111 Maybe you should make that one phone call to see who you should send letter to , Im sure someone will steer you in right direction as if you do not address it to the right person it could well end up in the bin . recorded delivery would make sure that person gets the letter ! .

My Endocrinologist didn't even know I had done the genetic test at the time of the appointment the I didn't even think to mention it. I did test to see if maybe thats why my aunt had suffered for all those years unfortunately she has passed away so died suffering with all bad hypo symptoms.. again i will tell you the Endo gave me a trial of Liothyronine due to all the symptoms I have, I did not have the genetic results back till 3 days after my appointment.. I did this test out of curiosity and was quite shocked I had it,

I do feel so much better with T3 but early days yet ! but I am not 100% better thats why I asked this question to others who had the same genetic result as me.

I have suffered since I started Levothyroxine as before i was diagnosed I didn't have any of these dreadful symptoms I felt sleepy like in a coma sleep I had no fat on me although I think by my hair and skin I may have been hypo for many years but thats all I had, i'm a lot worse with symptoms than before I was diagnosed, to which I was never told anything about it not a single thing only that the good news was that I get free prescriptions and that bad news I was hypo but Thyroxine sorted it out and thats it. I have many times since starting Levo been back to The GP and was palmed off with its your age (i was 40) ,HRT, quite a few other things then they were trying to say I had fibromagelia , I don't have any reflex which is a symptom of hypothyroid! where as fibromagelia they apparently have sensitive reflex, so I went searching to see how others were feeling and found out many more had suffered since taking Levothyroxine and on that journey I discovered there was this other drug, TBH I never even thought it was my thyroid because I believed the GP telling me it was my age etc I was even put on HRT 7 years later than I should of been because symptoms are the same ! .. So even if I had not had the gene I knew I needed something to stop all these symptoms and lucky I found a good ENDO,, so have not used the gene to get Liothyronine but I will tell you I feel much better on it but still not quite like I was before having Levothyroxine,


I'm getting quick responses from Regenerus who are aware of this discussion on Healthunlocked. I will put all updates in my original post.

Your endo was right to trial you on liothyronine and you may need more. It would be a good idea to ask your endo to monitor your ankle reflexes since as you say they are a good marker for hypothyroidism. More importantly, if they improve it will be very difficult for a doctor to claim it is a placebo response to liothyronine.

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I only know one thing relating to myself. I felt very ill on any dose of Levo and now feel well on NDT + T3. It's like waking up from a nightmare.

I have read your post and thank you.

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How much ndt you use and how much of t3? Iam on ndt too and have this gene but not getting better (better than I was on Levothyroxine only that’s for sure) but I think I might need to add t3...


I don't use T3 anymore only NDT 2.5 grains which is working for me. No weight gain, no hair loss, no ache and pains.

I still buy T3 every four weeks enough in case I need to use some. I was feeling OK on a

combination but had a bad batch and stopped.

I have no thyroid since 2015 before that I was fine no thyroid problems only a large

lump. I don't know anything about my genes apart from the fact that I am not allergic to anything as present.

What has a difference is raise my Vit D lever and taking Vit C


Thank you for sharing your expierence.did it take u a long time to reach 2.5 grains?


It's just to do with the orientation. It can be read plus or minus. 23andme for example always read in the plus orientation. Other snp databases are in minus, therefore different letters.

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I'm curious as to how your Endo was willing to prescribe you t3.

Was it after you showed him/ her you have defective gene or before?

And if before, how did you manage convince your Endo to give you t3.

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trelemorele i got my DIO2 results, printed out 6 copies, waved one copy in front of my GP, who then made a follow up appointment with an endo, I waved a copy in front of that endo, and was prescribed 6 months supply of T3 on the NHS.

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This is good news, although as you might have gathered I believe they are prescribing for the wrong reason! It's fortunate that you got this result and it led to a prescription of L-T3 that you clearly need.


Apologies jimh111 What do you mean? Why are they prescribing for the wrong reason? What should they be prescribing for me ?

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I believe they are correctly prescribing you L-T3. You clearly need L-T3 to get well but the DIO2 polymorphism does not explain why you need more than a few mcg of L-T3. Prescription correct, reason for prescribing wrong. You may not find out why you actually need L-T3.


Jim I hadn't had the results when they prescribed it, it was on my symptoms I hadn't even told the Endo I was having them done so wasnt why he prescribed it, It was my symptoms and the way I looked I should imagine.. :)


I am so pleased for you.

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I have many symptoms of still being Hypothyroid even on Levo and the symptoms only started after i was diagnosed Hypo, I have to spend days in bed as can not wake up and if i do a small task it wore me out competely so I would have to go back to bed, I get sleeps like i am in a coma and fine it difficult to even wake up, my hair is falling out, I have gained over 3 stone on Levo even though i eat less that 1000 calories a day , I could hardly walk as the pain was so bad , my body temp was 34,5 -35.6. My BP was 89/59. I was very pale looking, Sciatica and loss use of leg, My skin is dry, my nails dont grow and haven't for years , I had lovely nails and hair before taking Levthyroxine, and many more things have happened since then My memory had gone AWOL `I even went for an Alziemers test which i didn't have thank god,,

I have now been on all Vitamins magnesium included Im on all of them that were suggested to me so all those are good . I do feel a bit better with the mix t3/t4 but just wanted to know if others were prescribed 20mgs or should i try to get some more before Im completely out the Endos hands as it was a very long wait to see him it was about 6 months so want to strike whilst i still can ...

so I was not doing well at all on Levothyroxine, I went to the Endo he knew nothing of the Gene test I got prescribed T3 on my symptoms and he could probably see I wasn't looking at all well on T4

The results of gene test came back 3 days after I had been to the Endo, so he didn't know I had even had a test done as I forgot to mention it.

My TSH was 0.004 with normal range T3 T4, I was not having a life, I guess this is why the Endo let me have a trial and referred me back to GP .. I have given his secretary my results and heard nothing back as yet but she seemed interested in them but that was only 3 days ago so early days yet .


Pascha1, having looked at your symptoms in more detail it is quite likely you will need more liothyronine. Your signs and symptoms are way beyond the efffects of a DIO2 polymorphism, this is a bit of a red herring. I would give it a few weeks and if you are not much better ask for a further liothyronine increase and perhaps reduce your levothyroxine.

It's difficult to know the cause, it's clearly not just primary hypothyrodism as you are adequately medicated for primary hypothyroidism. Thyoid hormone action can be blocked by endocrine disrupting chemicals, substances in the environment which interfere with thyroid hormone processes. Whatever the cause your doctors need to look at your signs and symptoms and adjust your hormone dose to resolve these whilst ensuring you don't develop signs of over treatment. It's difficult to persuade doctors to adopt this approach, they become obsessed with blood tests (as do patients!). It's worth noting that dry skin is a very specific marker for hypothyroidism, so don't cover it up with moisturiser. If you have a photograph from before you became ill it may be worthwhile showing this to the doctor so they can see the difference.

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Hi Pascha Your question in this Post of yours has gone somewhat AWOL from your enquiry. Sorry about that. In my own case (and we are all different) I was diagnosed with DIO2 faulty thyroid gene from one parent (heterozygous) in June 2017. I already knew myself really but I definitely wanted it in black & white writing. I didn't feel at all well until I was taking 40mcg of T3 a day all in one dose. My body could not tolerate any T4 (levothyroxine) - it made me feel absolutely horrible. I hope that helps. Also I have replied further down the page to trelemorele about how I went about getting my 40mcg a day of NHS T3.

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I don't know my status but I remember reading that if inheriting from each parent then T3 only is required. I can only pass on what I've heard but I wonder if Diogenes can help us out here.



!Explanation of possible results

Results can be one of 3 combinations made up of two amino acid molecules known as T standing for Threonine and A for Alanine. These are further divided into;

Homozygous (same allele) TT or AA.


Heterozygous (different allele) TA .

(Other nomenclature for this test may show T as ‘wt’ and A as ‘vt’ – and mention wild-type or variant type which are scientific terms inferring neither good nor specifically bad effects as I have explained)


TT infers a genetic tendency to a good response to conventional thyroxine (T4) supplementation

TA infers a less than optimal response and that tri-iodothyroxine (T3) could be considered

AA infers a lower than average response and that tri-iodothyroxine (T3) perhaps should be considered

Any action in prescription changing MUST be discussed in light of symptoms and test results and made ONLY by the doctor in charge of your care.

Scientific status

At this time long term outcome studies on the relevance of this test and the benefit of changing prescriptions has not been established. There is certainly theoretical and growing anecdotal (patients and doctors seeing improvements) evidence of benefits.

You and your doctor may appreciate reviewing some of the literature here:

DIO2 PAPER 1 - jcem.endojournals.org/conte...

List of papers snpedia.com/index.php/Rs225014

Atlas of Genetics atlasgeneticsoncology.org/G...

Ala92Ala specifically - ihop-net.org/UniPub/iHOP/gi...


Pascha1 This might explain a lot, although I will wait for confirmation from Regenerus. The first two references you give are useful.

Where did you get this information from? Did it come from Regenerus?

To save time here is a cut + paste introduction:

ACGT is an acronym for the four types of bases found in a DNA molecule: adenine (A), cytosine (C), guanine (G), and thymine (T). A DNA molecule consists of two strands wound around each other, with each strand held together by bonds between the bases. Adenine pairs with thymine, and cytosine pairs with guanine. The sequence of bases in a portion of a DNA molecule, called a gene, carries the instructions needed to assemble a protein.

The original research (your first reference) tells us that the CC genotype is associated with better response to combined L-T3/L-T4 therapy that the TT genotype. Regenerus report TT and AA. This doesn't make sense! GG and AA would make sense as A pairs with T and C pairs with G - they would simply be reporting the other half of the pair.

The second paper you reference tells us:

the more common (T) allele encodes the Thr (threonine) and the somewhat less common (C) allele encodes the Ala (alanine)

From the information you just posted it seems they are using T standing for Threonine and A for Alanine !!! They are reporting the Threonine and Alanine molecules as alleles and also giving incorrect abbreviations 'A and T' instead of 'Ala and Thr'. They don't seem to know what they are doing.

In spite of all this mess, if the above speculation is correct the Regenerus test will be giving the correct results.


Yes that 1st one was from Regenerus and this one was from my counseller after askingfor a better description than I got on telephone,

Im not really understanding the science behind it all but it would explain a few things thats made me unwell on Levothyroxine and Gps blaming everything but my thyroid, being left under medicated would of made these symptoms worse and I went even really ill when my pharmacist changed my generic levothyroxine brand to Teva which made me very unwell and it happened to many others changing to that brand.. j, I now stick to the same one brand the new pharmacist won't give me ant other brand its on the computer now my old pharmacist refused to think a brand change would cause me to become unwell but she's all about saving money so i wont ever use her again ! .. but I should thank Teva and my pharmacist changing the brand over as I came searching to see if other were the same on Teva and I found out quite a bit about my symptoms and thyroid! , without them changing the Brand I may have just been ill and ignorant to it all till the day i died ,,

There are 3 possible results with a genetic result:

Homozygous Wild Type (which means there’s no SNP - i.e.: the result is ‘normal’)

Heterozygous variant (which means the patient has received one genetic variant from one parent - i.e: your result)


Homozygous variant (which means the patient has received a genetic variant from both parents).

The important information for your doctor is the HETEROZYGOUS result.

Beyond that, the T / A /G/ C are the bases which form DNA structures and they form pairs in a certain way.

T is for Thymine,

A is for alanine,

G is for guanosine

C is for Cytosine

The mentioning of TA is relevant in a laboratory - it means that a thymine has been replaced by an alanine, but knowing which nucleotide is in which position of the gene doesn’t tell you anything about the function of the gene and and it’s not relevant unless you are a geneticist studying in a lab.

i.e.: It doesn’t tell you anything about the way the gene works. The important information for the doctor is that you are heterozygous variant. This means that your DIO2 enzyme is less efficient than it should be. The enzyme does still work a bit, but it’s ‘sluggish’, so it’s harder for you to make T3 from T4. This might mean that you do better on a combination of T4 and T3 medication.

For more information on genetics and understanding about base pairs, there’s a very good book called Genome, by Matt Ridley.


In this case it's wrong to talk of 'wild type', it's not a question of standard genes and mutants, just minor variations. If you have the polymorphism the homozygous has more effect than the heterozygous which is sort of half way. In any event the polymorphism has minor effects but patients will do better with a little T3. Substantial symptoms are probably due to something else but if having the polymorphism helps get a liothyronine prescription then at least it is some use.


I have only just got a bit of my brain back from being on T3 its been along time dead !


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