DIO2 gene

So Ive done genetic testing purely to find out about a missing link in ancestry and what do I find? That I have the DIO2 gene. I didn't even know about his and now I know I have it, in fact I think I have 5 of the genes.

Through my own trial and error, I realised that I had a thyroid problem for many years although it wasn't showing up on any blood tests. No one seemed to care until the TSH did go a bit high. Apparently the DIO2 gene means you have the problem, it just doesn't show up on blood tests. Have I got that right?

Anyway, I took T4 for a couple of years and felt dreadful and in the end self medicated with T3 when I became a different person. I haven't been happy doing it all myself, blood tests, self medicating etc and in fact my figures all seem a bit weird now too. I feel I might be better on a combination but who on earth is going to prescribe tht?!

So, by chance I happen to have read about the DIO2 gene and how consultants will prescribe T4/T3 combination if they have the evidence to show and it so happens I had this genetic testing done and there it is.

I have persuaded my GP to let me see an endocrinologist anyway and I have an appointment in July. My GP doesn't know about this genetic testing, the findings etc because he wants nothing to do with T3.

So, I want to present this to the endo along with everything else and wondered what anyone else had found out about the gene. Mine seems to to a CT and I think CC is better????? Something to do with inheriting one half from one parent and one from the other and I think CT means its only from one parent.

Interestingly the DIO2 gene relates to osteoarthritis too. I have alot of problems with my joints/bones etc and also does my Aunt who has hypothyroidism. She has actually been diagnosed with osteoarthritis so I guess we share the same genes.

Any comments are welcome. Thank you.

32 Replies

  • As I understand it the DI02 polymorphism has a small effect on cognitive function in patients with primary hypothyroidism who are medicated with levothyroxine only. Thus, it doesn't make much difference.

    However, having the polymorphism does seem to get patients diagnosed and treated, sometimes with liothyronine. So, for the wrong reasons patients get the treatment they need.

    Having this polymorphism makes no difference to you having a form of hypothyroidism that wouldn't show up in blood tests although I'm certain there are forms of hypothyroidism that are not detected by blood tests.

  • Jimh111, I have the same problem as Number1. Although it's said that having the polymorphism doesn't make much difference and only affects cognitive function, I've found that taking T3 only has given me my life back. I no longer hurt all over, I have lost the weight I gained, my hair has grown back, I can think more clearly and I have the energy to walk 25 miles a week with our dogs.

  • Me too.

  • There's a page about it on the ThyroidUK website


    it includes links to the research and articles about it.

    I hope your endo knows about it.

  • Yes Ive seen that thankyou. Yes I hope my endo knows about it and more importantly Id like to stun my GP with it so he doesn't shut me down in panic every time I mention T3.

  • Numberone1,

    Many hypothyroid people appear to have a polymorphism on their DIO2 gene impairing conversion from T4-T3. Depending on the SNP's (mutations) this mean some patients may never be well on T4 hormone replacement alone. There are several known SNPs on this gene and probably more to yet be uncovered.

    The protein encoded by this gene belongs to the iodothyronine deiodinase family meaning it activates thyroid hormone by converting the T4 by outer ring deiodination (ORD) to T3. Because this faulty gene causes a deficiency of T3 within the cells, the usual thyroid hormone function tests will not show up a problem but both body and brain could be T3 starved..

    Most GP's will not know about this impairment and many endos will not entertain this evidence as an acceptance would force a need for a T3 prescription. You may be better approaching an endo that members have had positive experiences with. You can email louise.warvill@thyroiduk.org.uk for a list of sympathetic endos//doctors but it would be wise to ask endo's secretary if they are familiar with the DIO2 polymorphisms before booking an appointment.

    I have read about the osteoarthritis connection too.. You may want to test MTHFR as mutations are also common in hypothyroidism and cause an array of problems if not managed.


    Common Variation in the DIO2 press.endocrine.org/doi/pdf...


    ThyroidUK info on DI02 genetic test & further links


  • Thank you. I have managed to get a referral to a consultant that is actually ok with T3 so keep your fingers crossed that he knows all about this too.

  • Num,

    I always send evidence//test results, etc in advance of appointment via secretary. This way the whole consultation isn't used up by endo having to wade through loads of paperwork and if he wasn't to agree, it gives you further time to argue your case.

    Still take evidence to the appointment incase he hasn't had time//been bothered to read it.

    Lots of luck.

  • Good idea. I shall. I guess a resume of my problem attached so that if he gets time to read it, it cuts out some of the limited time we have.

  • Yes but kept really simple ... bullet pointed is good.

  • I've been self-medicating and taking T3 only for three years. I found out a year ago that I have the same DIO2 problem. Mine is only from one parent so it means I have a reduced ability to convert T4 to T3. I showed my doctor the results letter and he said, 'Well surely this means you need to be taking some T3.'

    I could have cheered! But then he said, 'I'll have to send you to an endocrinologist as I can't just prescribe you it willy nilly.'

    I saw Dr Allahabadia at Sheffield Hallamshire hospital only yesterday and he has agreed to prescribe me 40mcgs daily of T3. So having the proof of the conversion problem does make a difference. I would boldly March to your doctors and show him it. It has taken me seven years to get to this point and I feel like bloody waltzing into my doctor's surgery and singing, as loudly as I can, 'I was right and you were all wrong!'

  • I went private and got ndt prescribed on the strength of my di02 gene snp. It's fantastic and got rid of most of my symptoms (not weight unfortunately) and I feel great. However if you're going NHS I think it's variable and it's highly unlikely you will get ndt. I've seen 2 NHS endos, neither had heard of the di02 gene issue. One was completely uninterested and didn't take it seriously the other fascinated and said she'd do further reading including the papers I took in. So, check the Thyroid UK list and try and see one that's known to be sympathetic!

    Good luck

  • I wonder if these DIO2 polymophisms are enabling doctors to do what they wanted to but were afraid to - to prescribe L-T3. We know the effect of the polymorphism is small and that about10 mcg L-T3 would replace the T3 that comes from the thyroid. In which case the patient on 10 mcg L-T3 should be just as well as they were before any thyroid problems. This doesn't happen.

    However, patients do get well on much larger doses of L-T3, 30 mcg or 40 mcg or whatever. Clearly this is not due to the DIO2 polymorphsim although those with it are fortunate in that they have a key to unlock their doctors reluctance. The other 60%, without the polymorphism are the unlucky ones, their doctors are unable to rationalise a prescription of L-T3. (I don't know if I have a polymorphism or not, but I do require L-T3).

    The good news is that L-T3 is being prescribed and so doctors can gain practical experience of patients' recoveries which might start them thinking. We should bear in mind two considerations:-

    1. If you have one or both of these polymorphisms as far as is currently known they have little effect. You having a dreadful condition and needing high doses of L-T3 (or Armour) is probably unrelated to the polymorphism and consequently you do not need to worry about passing this characteristic onto your children.

    2. If you do not have this polymorphism you are just as likely to need T3 containing medication as those with the polymorphism. It will just be more difficult persuading a doctor. We should not forget these people, or undermine their situation by stressing the DIO2 gene too much.

    The above comments are academic. To answer Numberone1. I guess it would be a good idea to see an endocrinologist and mention the test results. I would stress how you have improved since taking L-T3, in particular point out things you can do now which you couldn't before. If the endocrinologist agrees to prescribe (on the NHS?) and monitor you then that will be great, it is always good to be monitored, have another opinion. It can also act as feedback for the endocrinologist, if we want them to change their attitudes they need to see real patients with real improvement on L-T3. If it turns out to be a dead loss then you haven't lost much, you can still carry on self treating.

  • I totally agree with you all. It should not be necessary to have this gene to help unlock the doctors views. It is because of their reluctance that I have had to do it all myself in the past. But I do feel now like I know my own body as this gene has been uncovered.

    Re whether it hides the problem, I read somewhere that by having that gene, you can have the symptoms etc and the problem but that it doesn't show up in the test results. So this concerns me with how long it took for me to get diagnosed and also concerns me re my daughter who has huge anxiety problems (I used to have those too which were resolved by taking T3). I suggested my daughter get a thyroid test done and of course it came back with good figures ie ones that I was happy with too that showed the thyroid wasn't a problem. But maybe it is if she has the DIO2 gene and its just not showing up.

  • Do all of you who've managed to get T3 prescribed on the back of the DIO2 polymorphism have a homozygous genotype (TT) or has anyone managed it with a heterozygous genotype (CT - just inherited from one parent)?

  • I got ndt with heterozygous as while t3 has a greater affect on homozygous people it's also shown to be very beneficial for heterozygous

    Also, the ndt increased my mental agility hugely not by a small amount. Whether this is due to my gene defect, ndt being a better med or placebo effect is difficult to say on a case of 1 but the di02 effects should not be dismissed as minimal on my opinion (jmh111)

  • "I read somewhere that by having that gene, you can have the symptoms etc and the problem but that it doesn't show up in the test results. "

    I've never seen this and it doesn't make sense. Such subjects would comprise of 40% o f the population and the effect would be very mild. I suspect that most people with symptoms and normal blood test results suffer from endocrine disruption from environmental toxins which mimic thyroid hormones. This is far too big a subject to take on here and it will be a number of years before any advances are made.

  • I thought the gene was in 5 per cent of the population (approx) not 40 per cent?

  • We all have the gene ;-). The TC variation in about 40% and the CC in 16%. See ncbi.nlm.nih.gov/pubmed/?te... . The paper is open access so you can click on the Full Text Links icon and obtain it for free.

  • Mine is CG so what does that mean? I think it means half of the C is still there ie inherited from only one side.

  • Hi there

    Each gene has a pair on your dna strand and you get one of each pair from your parent. If you have heterozygous you have one with the defect and one without; if you have homozygous you have both the same ie in this case both with the same defective gene. Genes have a letter (not all letters are used but C and G are) but can you confirm the context of CG just so I can make sure that I'm giving you the right info?

  • What do you mean by the context of CG. On the list showing the gene and the snp it has at the side of it whether CC or CG and then some of mine (there are 5 snps) are CC and some CG. Does that make sense?

  • Ok - my test was a bit different and clearly stated:

    heterozygous variant genotype in relation to the DI02. The letters after it relate to the gene molecules in it. I wouldn't get too hung up about it as it just details what is in there. There are different molecules that make up the genes that have different letters (GATC); further detail on the difference between them goes far beyond my biology O level as we mainly concentrated on dominant and recessive genes :-)

  • Sorry - typing on a phone so should have been gene snp/defect obviously.

    I have a copy of that paper as I used it to get my prescription of ndt.

    There isn't any studies (that I have seen) that indicate whether:

    A. The reported 12.5 per cent of hypo diagnosed patients who don't find t4 resolves all symptoms have the gene snp (either hetero orhomozygous). Admittedly the 12.5 per cent is anecdotal (from Thyroid UK survey last year) but other studies put the percentages as between 5 and 15 per cent

    B. Whether there are hypo diagnosed patients with this gene snp that do feel well on t4 mono therapy

    C. What other factors (other gene snp/environment etc) could be at play that affect whether t4 mono therapy is appropriate

    D. Whether the incidence of this gene snp is in a higher proportion in the thyroid malfunction population than the incidence in the general population

    As someone coming from a family where every female over 35 has had thyroid issues back to my grandmother (known, not sure about further back) I'm extremely interested in whether genetics plays a part. Particularly since we don't get primary hypo and therefore take some time to get diagnosed. However there seems to be little research into this since the majority of the medical profession appear to have the opinion that hypothyroidism is a simple, non serious condition easily solved by t4 and therefore warrants little further research.

  • Hi

    I've had a look through the paper and it states that people were selected according to genotype but also indicates that the gene issue may only affect less than 20% of the population. It does state that 16% of the study population had the rare CC type but this is not the UK population but those selected for the study as I read it. If they were looking for a control group of 'normals' with sufficient of those who had the deficiency and had access to the dna testing (which it appears that they did) they could have selected their groups according to genome.

    If their test group is representative of the population at large then their central thesis (that the issue with people not doing well with T4 mono therapy is not recognised since this affects less than 20% of the population) is proved incorrect by their paper which shows a far higher incidence of the defective genes.

    As such I suspect that they selected people with the gene snps; which they then further refined (as they found no correlation between DI01 and DI03 snps and improvement on the combo therapy) to only look at the DI02 issue.

    I only think it affects around 5% of the population based on a comment by my endo that it affected around 5%. I have tried to substantiate this figure by looking for research or guidance for when I made my complaint to the NHS ombudsman but Google did not come up trumps. Would like to get an idea of the actual numbers if anyone knows them and can point to a source?????

  • I have one faulty DIO2 gene. My understanding is that the TSH won't necessarily indicate a problem.

    In my case my T4 was below range. The poor conversion issue will have affected my T3, but of course that wasn't tested for many years and has mostly only reached mid point.

  • that is exactly what happened to me. My T4 was always low (marked low by hospital testing centre) but I was never told, continued to have symptoms etc. I have 5 faulty genes apparently. My understanding also is that if you have this, the blood tests wont indicate the problem.

  • Hi there,

    I too have a faulty DI02 (haven't had the other tested as yet), was symptomatic for 7 years with the latter 4 as severely symptomatic but although my FT4 and FT3 were below range (most of the time or 0.1 above the bottom) my TSH didn't rise. This caused major issues with getting diagnosed

    I finally changed GPs practice and found one that had actually read the NICE guidance which reproduce below ( have italicised and put in bold the important bit). As such he 'trialled' me on 25 of levo and got me up to 100 before my FT4 limped into the normal range.....(and yes I'm not on my phone today so it makes it a lot easier to include stuff)

    NICE guidance below:

    TSH 10 mU/L or less

    How should I manage someone with subclinical hypothyroidism who has a thyroid-stimulating hormone (TSH) level of 10 mU/L or less?

    Confirm by repeat testing of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels, with the addition of measurement of thyroid peroxidase antibodies (TPO-Ab), 3–6 months after the original result.

    Levothyroxine treatment is not routinely recommended.

    Consider offering levothyroxine treatment if:

    The person has a goitre.

    Their TSH level is rising.

    The woman is pregnant or planning pregnancy (see Scenario: Preconception or pregnant).

    Consider offering a trial of treatment if the person has symptoms compatible with hypothyroidism.

    Prescribe treatment for a sufficient length of time to be able to judge whether there is symptomatic benefit, see Prescribing information.

    Only continue treatment if there is a clear improvement in symptoms.

    If treatment is continued, once stable, measure TSH annually and alter the levothyroxine dose to maintain the TSH level within the reference range.

  • and I have developed osteoarthritis 😕

  • This protocol is absolutely no good for me as my T4 looks good by blood tests and my T3 remains stubbornly mid range while the GPs get their knickers in a twist about my low/suppressed TSH. In the meantime I still have a long list of increasing symptoms.

    Accordingly I have resorted to self-medication 😕

  • Hi, did you use regenerus? How long did it take to receive your results?

  • No I got mine from 23andme

You may also like...