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Thyroid UK
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TSH Normal / defective DI02 gene

Hi, I have been experiencing hypo symptoms (all of them) for around 4 years. I managed to get my gp to treat me with T4 which improved my symptoms, but not completely. He stopped the meds 4 months ago saying I didn't need it because I wasn't really hypo.

Since then symptoms have returned.

Did the DI02 test and found I have one defective gene.

My question is:

* When I read the research it sounds like the gene just affects how you feel psychologically - so does it mean it won't affect you musculoskeletally? *

I have psychological and musculoskeletal symptoms. I have head pressure/tired brain/cold/tired/leg pain/leg burning/throat pressure/constipation/pin-prick sensation in fingers and toes/carpal tunnel in bed - and I am very sad to think I might never get to the bottom of it.

Does anyone out there understand the interpretation / implications of the research?


21 Replies

Your doctor is uneducated in the D102 Gene. Some extracts for you and he needs to be educated.

As far as I understand reading these few extracts if that you are not able to convert your healthy T4 into healthy T3, which would result in you not being able to function due to the receptor cells not having T3 or sufficient. Our brain also contains the most T3 cells:

Various guidelines recommend that you can only have this test done if you receive pre and post “Counselling” and Regenerus Laboratories can organise this for you if you don’t have access to an experienced genetic and registered health professional.

“Counselling” will include a questionnaire prior to your test and once your sample has been analysed your report will be discussed with you by one of Regenerus Laboratories genetic counsellors.

If your report shows that you have inherited either one or both faulty genes, it may be worth taking your report, along with the research article, to your GP or endocrinologist and asking for a trial of T3 to be added to your levothyroxine.

Please let us know how you get on!

Another excerpt from the same page:-

To explain this paper briefly, the DIO2 gene activates tri-iodothyronine (T3) and the researchers found that a tiny fault in this gene could mean that although the body gets enough T3, the brain doesn’t.

and another

The researchers found that patients on levothyroxine (T4) alone felt worse if the faulty DIO2 gene was inherited through one parent and worse still if they inherited the faulty gene from both parents.

Because this faulty gene causes a deficiency of T3 within the cells, the usual thyroid hormone function tests will not show up a problem. This means that your TSH, FT4 and FT3 blood tests will look normal.


If your report shows that you have inherited either one or both faulty genes, it may be worth taking your report, along with the research article, to your GP or endocrinologist and asking for a trial of T3 to be added to your levothyroxine.

The study concluded,


I would hate to know how you are coping with no levothyroxine at all, except that I think he should prescribe T3 only if you cannot convert T4.


Many thanks for your reply. It's difficult to think straight and interpret genetic research when you're not a doctor and your brains feel like lumpy custard! I did use regenerus and one of their counsellors. She seemed to think that the one faulty gene would be felt physically and mentally. I am trying to get another appointment and will show him all the research. Best wishes !


As it is relatively new - he probably wont have any idea but he has to prescribe T3 (my view - I am on T3 only and don't have a defective gene as far as I knew and feel well now.) Your brain, in particular, needs it as well as all your cells.

Hope you are successful.


Did you have to see an endo or did your gp do that for you?


The Endo did prescribe T3 initially to T4 and I felt a big improvement that I decided to try T3 only so I had to source my own initially. I also tried some NDTs too in between. It does take some time to find what makes you feel well. If you have a defective gene your GP may refer you to an Endocrinologist. If so, put a new post asking for info by Private Message in an area which you live for a recommendation. You may be lucky.

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Thanks for that. Saw GP this morning who was a bit sceptical about the various bits of research and my symptoms. He did agree to a blood test to look at T3 and T4 and TSH. I told him I want to try it to see if it helps, hopefully he will be amenable when I see him for my results, if not, I will try to get a referral!


If/when you are considering a referral, maybe put a new post asking for a Private Message to be sent to you if anyone can recommend an Endocrinologist (NHS or Private) in or around your area.



once your hypothyroid it does not magically cure your hypo for life

Did you take your thyroid meds in the 24 hrs before your last test because YOU MUST NOT TAKE THYROID MEDS for at least 24 hrs before a test or doctors will reduce doses


Thanks, I read not to take it that day, so I didn't. I managed to get down to about 1 from 3.75, and my muscle pain and many of the other symptoms got better, but not completely. That's why I would like to try T3, just to see if they all stop, then I would know I was on the right track!


The research shows that if you are medicated for primary hypothyrodism (failing thyroid gland) with levothyroxine only and you have both polymorphisms in this gene you could have some impaired cognitive function. If you have a polymorphism in only one of your two genes then the symptoms are much less.

However, there is some research (sorry can't remember reference) that shows that children who have this polymorphism and lower thyroid hormone levels suffer lower IQs.

So, this research shows that if you are 'adequately' medicated with levothyroxine you may still suffer impaired cognitive function. Importantly, it looks like that if you are somewhat hypothyroid and have this polymorphism you will do worse than someone who doesn't have the polymorphism.

The fact that you improved when your GP treated you gives evidence that you do have hypothyroidsm. Your signs and symptoms are more important than any blood tests.

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Thanks, I thought it might only affect cognitive function - that's how I interpreted the research, but the counsellor seemed to think it would effect tissues all over the body - that's why I was confused. I am trying to get an appointment with the GP to show him my results and the research. I will update the thread after that . . .


Thyroidquest, It's highly unusual to to be 'undiagnosed' after being treated for hypothyroidism for 4 years. Your symptoms are classic hypothyroid symptoms. Have you had thyroid tests since stopping Levothyroxine? I would recommend you request your GP to test TSH, FT4 and FT3 in view of your DIO2 gene impairment. If your FT3 is low ask for referral to an endocrinologist because the gene impairment means you will need T4+T3 combination therapy to be well. Alternatively you can order private thyroid tests from Blue Horizon and Genova via


My understanding of DIO2 impairment is limited but I believe it impairs T4 to T3 conversion. Low T3 is the reason we experience hypothyroid symptoms both psychological and physical. The first extract discusses how T4+T3 combination therapy may enhance psychological wellbeing in patients with impaired DIO2 and the second discusses the possible impact on bone mineral density due to low T3 caused by DIO2 impairment.


Our results require replication but suggest that commonly inherited variation in the DIO2 gene is associated both with impaired baseline psychological well-being on T(4) and enhanced response to combination T(4)/T(3) therapy, but did not affect serum thyroid hormone levels.


In summary our data suggest that a decrease in local

availability of T3

potentially owing to a D2 polymorphism may

result in increased bone turnover and decreased bone mass at

the predominantly cortical femoral neck. We believe that our

study provides additional information on the role of D2 in bone

metabolism and the functional consequences of the D2 Thr92Ala

polymorphism, supporting a role for D2 in mature bone cells.


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Hi, thanks for your response. I was only treated with Levothyroxine for just over six months, prior to that they ran all sorts of tests (including thyroid) which were within normal ranges. In the end, because the symptoms seemed so typically hypo, he grudgingly agreed to try Levo, but had to comment that most women ask for it to lose weight. If I get nowhere, I might have to find a private endo but don't want to waste money on someone blinkered. I shall take your research references with me to my next appointment, thanks again...


Thyroidquest, his attitude stinks. It might be as well to find a GP who is prepared to consider your symptoms properly rather than assuming you are looking for weightloss aid. It's likely T4 wasn't working properly for you because of the DIO2 impairment but he appears to think it wasn't working because you aren't hypothyroid. Very Catch 22 :(

Email louise.warvill@thyroiduk.org.uk for a list of NHS and private endos recommended by members.


Thanks Clutter, I have just emailed louise. It is catch 22!! Most days I try not to dwell on how impossible it all seems, but this forum is very helpful, great to have the support of a community at last, I am sure I will get somewhere . . . .


Just been to see the GP. Was sceptical but is testing T4 T3 TSH again next week and I'll take it from there. If I get nowhere I will go see an enlightened endo. I will know I am on the right track when my thoughts are clear, my body hair returns and the ringing in my ears stops etc, etc


Just a general comment on DIO2, the gene that's responsible for type-2 deiodinase (D2) as it can get very complicated and confusing.

A common DIO2 polymorphism (minor variation in the gene) leads to reduced D2 activity. Patients with this polymorphism in one or both of their genes have the same serum levels of TSH, fT3 and fT4 as the rest of the populations. So it doesn't have a big effect. However, D2 - like D1 and D3 - takes place within the cells, D2 more so. Different cells have different levels of DIO2 expression and D2 activity. That is, some cells contain more DIO2 genes, some fewer or none at all. Similarly some genes may have high D2 activity (and so be able to use T4) and some have none (and so are totally reliant on serum T3).

So, if someone has this polymorphism they will a different cellular thyroid hormone profile. Eventually the research may show e.g. they are more or less likely to get diabetes or osteoporosis etc. Just like someone with blue eyes may be more susceptible to skin cancer.

What has already been found is that hypothyroid patients with the polymorphism (particularly in both genes) have mild cognitive impairment if they are treated with levothyroxine only. There is also evidence that this polymorphism combined with iodine deficiency can lead to lower IQs in children. I'm sure other links will be discovered, some beneficial, some not. What does seem to be relevant is that if you have this polymorphism (particularly in both genes) and your hormone status is suboptimal then you are more likely to be hypothyroid, in some tissues at least.

Actually I don't think most of the problems we see in these forums are due to this polymorphism which is only responsible for minor changes in hormone status. Most patients are experiencing substantial symptoms, in many cases severe. The DIO2 polymorphism does not explain these patients illness. Specifically, if you used to be OK before your hypothyroidism and now receive sufficient T4 and T3 to bring your levels back to where they used to be then you should be OK now. This is not so for many patients, so I don't think the polymorphism is to blame, it certainly isn't in the 60% of the population who do not have this DIO2 polymorphism. There has to be other reasons.

I hope this helps. I think the DIO2 polymorphism is responsible for minor symptoms which would resolve on around 10 mcg L-T3 or less. However, if finding out you have this polymorphism helps your doctor justify prescribing T3, which you may need for other reasons, then so be it. The important thing is to make the patient better, the academic debate about how it works can take place later.


That was very informative and thanks for taking the time to write it. I tried but failed to find that level of information on Google. GP is rechecking bloods next week and may be persuaded to treat me based on my symptoms. They did improve on T4 but didn't go completely. I still had ringing in my ears (constant for 4 years) and headaches. I'd like to try T3 because if that resolves these symptoms, I think it would be fairly diagnostic. (I don't think the constant tinnitis would go with a placebo effect.) However, as the serum T4 reading was within normal range I am not sure whether I can really be hypo despite all the symptoms being indicative. Will post blood results when I have them . . .


There is a lot about DIO2 "out there" but not always easy to find. For example, these three chapters of Thyroid Manager each has relevance:





Does anyone know why no one has attempted to replicate the paper?


Now that's what I call detail. Thanks!


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