Dio2 Gene

[Stace268]

Hi

What does the TT genotype mean in laymams terms to T4 to T3 conversion.

Has anyone had Dio1 Dio2 and Dio3 etc tested

[Hashiboy]

Hi Stace, yes I tested positive for this. It’s a fairly common genetic variation or polymorphism (about 30%) of people have it. The jury is still out on its real effects but in rats bred with this variation in the lab they can’t efficiently convert T4 to T3 inside cells. So blood levels of T3 can look good but they are hypothyroid at a cellular level. This hasn’t been shown in humans. My endo put me on T3 and said because I couldn’t get well on T4 and because of this genetic variation it was likely that I wasn’t converting T4 to T3 at an intracelluar level (inside the cells of my brain, heart etc) and had ongoing hypothyroidism at a peripheral tissue level. I feel a million times better on T3. But as I said the science isn’t there yet and there’s no controlled trial to say people with this genetic variation really do better on T3. It depends a lot on the endo. Hope that helps.

[Stace268 in reply to Hashiboy]

Hi

Yes it is helpful thank you.

Did you have any of the Genes tested like Dio1?

Many thanks

[Hashiboy in reply to Stace268]

Yes I did by chance as part ofa research project into COVID that I have blood for. I asked the researchers to check for me and they kindly did. I carry the variation.

[Stace268 in reply to Hashiboy]

Did they tell you anything about the Mitchondrial DNA linked to TT genotype? I think i will look at the Dio1 testing too

[DippyDame in reply to Hashiboy]

academic.oup.com/jcem/artic...

Re: Dio2

[SlowDragon Administrator]

Some endocrinologist will take Dio2 results into account, others won’t

thyroiduk.org/deiodinase-2-...

thyroiduk.org/help-and-supp...

regeneruslabs.com/products/...

Email Thyroid U.K. for list of recommended thyroid specialist endocrinologist and doctors who will prescribe T3

[e-mail]

[Stace268 in reply to SlowDragon]

Thank you. I think id need find one that puts me on NHS list as i cannot afford private ongoing

[SlowDragon Administrator in reply to Stace268]

some on that list are NHS only, some are NHS and private

Roughly where in U.K. are you?

[Stace268 in reply to SlowDragon]

I am south east, east sussex

[SlowDragon Administrator in reply to Stace268]

so there’s some on list near you

[Titaniumfox]

TT is the 'good' genotype to have for the DIO2 gene. It's the CC polymorphism that indicates an impaired ability to convert T4 to T3. You don't have that so you are fine (with respect to the DIO2 gene, at any rate!)

I haven't had the DIO genes tested as such, but when I had my genome sequenced many years ago it contained the DIO SNPs of interest so I have that info from it. I think those genes are no longer included in the genome sequences, however. You'd have to look into that if you are considering getting the info via that route.

[Stace268 in reply to Titaniumfox]

I did look into it and found its linked to mitchondrial DNA and fear for my son as he is struggling and im not sure its just autism. I did not take Levothyroxine through pregnancy 😔

[McPammy]

I took the DIO2 gene test and I am positive. My T3 blood result levels was very low, I was only converting 8% of T4 levothyroxine to active T3. I could barely walk or sit up. I had no energy to hold my own body up. I went private and was prescribed liothyronine T3 combined with levothyroxine T4. Oh boy it’s made a huge difference to my life. I’d been diagnosed with hypothyroidism for over a decade and on levothyroxine only. I would have really bad periods of lack of energy. No Dr I saw knew what my issue was within the NHS. Going private and getting a very successful trial of liothyronine T3 was a complete game changer for me. I’m glad I know the reason why I was struggling on levothyroxine, I had this faulty gene DIO2 which meant I was struggling to convert to the most important hormone T3. Now I’m full of life, feel youthful and very energetic.

[Stace268 in reply to McPammy]

I am glad things have improved for you and you found the cause. I felt terrible through pregnancy and afterwards as well so know you must of felt awful. I think mine is a similar scenerio as Hashiboy where its a bit more elusive.

The gene results ive just posed on here are confusing.

[Rita-D]

yes I did. I’m heterozygous for DIO2. My endocrinologist was very resistant in prescribing T3. Said no point unless you have a polymorphism. Told him I did. I’d had private testing. He said “oh you won’t be able to convert T4 to T3”. I’d been trying to get T3 for 4 years! After a bit of an issue ( it was in November 2017, when the CMA were investigating overpricing of T3), I was eventually prescribed it. I’m on combination therapy and it’s changed my life!

[Hashiboy in reply to Rita-D]

Good to hear a positive story

[DippyDame]

The TT result means you have no defect from either parent so no impact on conversion

CC result means you have inherited the defect from both parents ( homozygous) so the impact on conversion is much greater so the addition of a little T3 usually helps

A TC or CT result means the defect came from one parent( heterozygous)....impact on conversion may be slight.

A CC result is more likely to help achieve a T3 prescription

I tested Dio2/CC/ homozygous and take T3...which my endo said I did not need!!

In general medics are not up to speed with thyroid genetics... but should be!!

The report on your result is correct....T3 is not required.

This might help further

paulrobinsonthyroid.com/dio...

[Musicmonkey in reply to DippyDame]

prescription

'I tested Dio2/CC/ homozygous and take T3...which is not prescribed!'

You should be prescribed on the NHS. Have you tried more recently?

[DippyDame in reply to Musicmonkey]

I know you were trying to be helpful and I really appreciate that .... but, that this is the reality

I'm afraid what should happen and what happens in reality can be very different.

My endo said I should take levo....his knowledge was seriously lacking

I'm now on a stable dose and have no wish to be told to reduce/ change my medication because I've been there and know what happened!

It is beyond scandalous!

I need a supraphysiological dose of T3 that the NHS would not, without a miraculous change of policy, prescribe....or pay for!

So, to stay stable, functioning, and indeed alive, I have to self medicate.

My GP knows and understands this and accepts my right to exercise Patient Autonomy.

This is not being dramatic....it's life as I ( and many others in a similar position) live.

Thank you!

[Stace268 in reply to DippyDame]

Any ideas re Dio1 impact? As im yet to have this tested, TT gene is associated with Mitchondrial DNA which is ironic as i have gypsy romany ancestory directly on both parents side and apparently it stems right back to egyptians. Im white caucasian or i thought i was.

[Stace268 in reply to DippyDame]

Sorry just seen this link it confirms about the Dio1 gene so i may infact need T3 and the report is not accurate

[DippyDame in reply to Stace268]

What link?

I'm sure you can take that report as accurate given you have been found to carry the Dio2 / TT....not inherited

[Stace268 in reply to DippyDame]

How is it accurate if its missing the whole picture regarding Dio1? And the link you put on here https%3A%2F%2Fpaulrobinsonthyroid.com%2Fdio1-and-dio2-gene-defects-and-testing-them-for-thyroid-patients-with-suspected-t4-to-t3-conversion-issues%2F

[DippyDame in reply to Stace268]

The report refers to the Dio2 polymorphism

Dio 1 is another test

[Stace268 in reply to DippyDame]

I know it is a Dio2 test but what i am saying is the wording 'appears' Id only need T4 may be inaccurate if I have a faulty Dio1 gene?

[Stace268 in reply to DippyDame]

I have the Dio2/CC?

[DippyDame in reply to Stace268]

Drat it....sorry, I did initially type the wrong thing... TT it is!!

However it doesn't alter the fact that the comment is correct on the BH report.

You confused me by referring to the Dio1 gene!

I now understand what you mean by...

How is it accurate if its missing the whole picture regarding Dio1?

I'm not sure there is a definitive answer to this, note the word " possible" as Paul writes...

In the case of the DIO1 and DIO2 genes, if the SNPs have mutations it is possible for any D1 or D2 enzymes produced are compromised in their quality, resulting in lower conversion capability from T4 to T3. Researchers are continuing to look at the DIO1 and DIO2 genes and their polymorphisms.

Another way of assessing T4 to T3 conversion is to compare FT4 with FT3

High FT4 with low FT3 = poor conversion

We don't have any labs other than TSH is .1.66, T4 18. T3 .4.9, 

Please can you now add reference ranges, they vary from lab to lab

[Stace268 in reply to DippyDame]

I will add more ranges though i know in my early twenties my T4 dropped out of range at 9 or lower and NHS DR offered T4 which i refused. These results were not kept on NHS system as had been longer than 6 years perhaps.

So i do have a faulty Dio2 gene variant RS225014 TH92Ala though it is not on the face of it considered to be bad, is that right? I am finding it hard to find basics

Yes youre right re FT4 and FT3 conversion which both endocrinologist said it was poor i will find the paperwork and upload.

[Stace268 in reply to DippyDame]

T3

T3 declining

[Hashiboy in reply to DippyDame]

DippyDame that's the best explanation of that stuff I've ever read. Thank you, makes more sense to me now.

[DippyDame in reply to Hashiboy]

Glad it helped.

[SlowDragon Administrator]

I test positive for Dio2 as heterozygous …so inherited from one parent

I had already been prescribed T3 on NHS…..was unable to walk after 24 years very poor health on just Levothyroxine with only TSH tested

Only joining this forum and getting full thyroid and vitamins tested did I make progress

Low Ft3 and high Ft4 showed poor conversion

Private endoscopy confirmed severe gluten intolerance….no gut symptoms

Hashimoto’s, vitamin D, folate and B12 deficient, psoriasis, Mitral valve prolapse, lipodema etc etc

It’s essential to maintain optimal vitamin levels for good conversion of Ft4 to Ft3

Have you tried gluten free diet and/or dairy free diet

Splitting levothyroxine into two doses - half waking and half at bedtime…..can help improve conversion rate

[Stace268 in reply to SlowDragon]

This forum is very good on knowledge as life experience counts sometimes more theory and practice. Relieved you and others have made good progress after so many years.

I had anemia as child which affected me and my son and his dad had the same. My son and me both struggling now.

You make good points as far as im aware all vitimins in top quarter no coeliac and im trying switch to no gluten as my son has difficulties too but difficult cut out dairy as i had low vit D below 25 and feel substitutes are low in protein.

I may try the halving but routine often means end up eating later then would like.

[Stace268]

As Hashiboys post Dio1 defect can mean problems converting in the liver so im thinking as with having T3 low normal means this could be the case but it seems steep 140 or whatever it is from Blue Horizon when ive just paid 80 for this test

[SlowDragon Administrator in reply to Stace268]

was this a reply to anyone in particular….you need to click on reply button

Are you saying you have done this test …..via Blue horizon?

[Stace268 in reply to SlowDragon]

Sorry it was a universal reply and no ive only done the Dio2 test, though thinking i need Dio1 though after having paid 88 for Di02 from another company its a lot to pay 140 for Dio1 from Blue Horizon.

[helvella Administrator Thyroid UK in reply to Stace268]

Earlier I posted this reply on the other thread discussing such testing:

If you want to go further than a single test, you might consider Whole Genome Sequencing.

By the time you have covered a tiny number of specific tests, you could get the whole thing! I think the current least expensive is around $400 (which might be £400 or more at present).

I don't want to effectively point you at any one supplier. Both to avoid effectively advertising and because I have no idea the benefits and reliability of one over another.

[Stace268 in reply to helvella]

*jaw drops to the ground* how much 😄

[helvella Administrator Thyroid UK in reply to Stace268]

Is that jaw drop because you get towards 3 billion base pairs analysed for that cost?

Or that £400 is a lot of money if it doesn't produce what you see as direct benefits?

Each of those has some sense to it!

[Stace268 in reply to helvella]

How easy is it to analyse the main concerns on the report is it vague and is there variables on what could trigger or leave that gene dormant. I have cancer in my family and I dont think id want to know in regards to that though ive heard untreated anemia or thyroid can put a lot of stress on the body.

[helvella Administrator Thyroid UK in reply to Stace268]

I'm afraid I don't know - it's not something I have done. If you want to make sure you only see some parts, you might need the help of someone who can interpret with and for you.

[DippyDame in reply to helvella]

I acquired my raw genetic results and then the interpretation, from two different sources, for less than £400!

I'm still working my way through it when I have time!

Interesting... but not life changing.

Oh, and pleased to unexpectantly discover I'm a tiny part Norwegian!!

And not so pleased to find " intolerance" in my genes... though my family have always jokingly said "beware, she doesn't tolerate fools gladly". My elder son has inherited that one! Must be the Viking genes!

[helvella Administrator Thyroid UK in reply to DippyDame]

Was that the whole genome sequencing (WGS)? No just what 23andme, Ancestry, etc. offer at around the £140 mark? (They are just a selection of the information. Much less than WGS.)

If so, please let us know the source(s).

[DippyDame in reply to helvella]

I stand corrected!

It was Ancestry... screeds and screeds of raw data

I used Sequencing for interpretation

[helvella Administrator Thyroid UK in reply to DippyDame]

You get an awful lot of information for the money from Ancestry et al. They can be very interesting and potentially helpful. Just a matter of luck whether they cover the specific genes you care about right now - and then again, in the future.

[stockman27]

I have had this test and I am having a bit of a bad thyroid storm at the moment. My experience of end and gps are as long as your TSH is in limits then you are ok, even if you are on your deathbed .

[Hashiboy in reply to stockman27]

stockman27 Hi there, really sorry to hear you are feeling so unwell. I coasted along feeling terrible on T4 for years. It dawned on me I wasn't getting anywhere and had handed my linee and health over to medics who were probably dealing with patients in life threatening need with next to no resources. I realised I'd have to be much more active. So insisted on seeing a nhs endo which was some help but in the end I arranged a private consultation witha consultant from the list Thyroid UK provide. It was about £250 and my GP and NHS endo accepted the advice to try T3 (my NHS endo knew he could then discharge me and get on with seriously ill diabetics). It's your health and your life, insist on a referral from your GP and if it's financially possible pay for help. My biggest regret is waiting for long on T4 and having such lousy quality of life. I just don't think doctors know much about thyroid problems so we have to be very very clear about the help we want. Good luck.

[DippyDame]

Looking at the Frees on both lab sheets...

18/10/ 21

FT4 is 50% through the ref range

FT3 is 21.62% ditto

22/12/ 21

FT4 is 63.64% ditto

FT3 is 16.22% ditto

Were you medcated and did the dose change between tests?

In each case FT3 is abysmally low

Both Frees should be approaching 75% but with the caveat that we are all different so this will vary a little

FT4 on 12/12/ 21 has risen either by additional hormone or perhaps becase you have thyroid autoimmune disease ( aka Hashimoto's) which can cause hormone level fluctuation.

Bottom line....your T4vto T3 conversion is poor and you need to address this

First you need to test and optimise vit D, vit B12, folate and ferritin.....this may/ should support and impove T4 to T3 conversion

That done consider having a full thyroid test to include....

TSH, FT4, FT3, vit D, vit B12, folate, ferritin and thyroid antibodies TPO and TG ( the latter 2 test for Hashi's)

Whatever is causing that poor conversion the Dio2 gene does not appear to be the cause....it may very well be low nutrients!

Your genetic test result does not show a Dio2 variant causing conversion impairment.....that would be a CC, CT or TC result showing you inherited the polymorphism. You have none of these, just a TT result which shows you have no defect here from either parent.

Personally I wouldn't get hung up on genetic tests at this stage but instead concentrate of the poor conversion clearly expressed by the high/low FT4/ FT3 comparison

You must first optimise essential nutrients listed above!

You are hypothyroid and need initially to be medicated with levo

It maybe that you need to be prescribed levo along with optimising your nutrients if deficient.

Down the line it maybe that you need to add a little T3 to a levo dose.....too soon to conclude that though.

Right now it's not entirely clear what is taking place

I'm no expert (but I'd suggest the cart is overtaking the horse here!) so to get things lined up it might be best to start again with a full thyroid test the results of which can then be analysed to see what is going on.....and to work out what treatment is needed.

Many of us test privately...

thyroiduk.org/help-and-supp...

Sorry, I'm ranting on a bit but hopefully it points to a way forward.... out off the place you are currently in.

Good luck!

[Stace268 in reply to DippyDame]

The last and latest is TSH is .1.66, T4 18. T3 .4.9 thats after 2 years of levothyroxine, is that still poor conversion?

I also agree re vitamins although most are within range now top quarter but vit D was ultra low at one point.

Many Thanks

[DippyDame in reply to Stace268]

Improving...

Suspected low vit D....culprit of poor conversion.

FT4 now 63.64%

FT3 now 48.65%

How much levo?

An increase might now sort it.

Keep going!

[Stace268 in reply to DippyDame]

100mg Levothyroxine but i weigh 15st so think im under medicated. Though as T4 high doctor probably concerned Arythmias as heart disease in family

[flitter-maus]

Trying to get my head around this too! I was wondering if we had these genetic defects before becoming hypothyroid would we always have had a problem converting? Does it only become an issue when we become hypothyroid? I’m hashi and became hypothyroid 3 years ago. Never had a test for faulty genes but need T4 and T3 to be well.

[perardua]

Is this the Regenerus test?