Is this standard NHS response to DIO2 result?

[NWA6]

Back story. Hashi’s - 10yrs, sometimes good but never been ‘optimal’. Last few months the T4 just doesn’t seem to be as effective.

TSH - 2.1 (0.3-5)

FT4 - 16.8 (9-24)

FT3 - 3.9 (3.5-6.5)

Over the years my FT3 has been 3.9, 3.5, 2.5, 3.9 and 3.8

So this led me to think about conversion so I had the DIO2 test and I have a faulty gene from one parent which MAY have and effect on conversion. I think it’s clear that no matter how much T4 I take (and I’ve always pushed for more) my FT3 just doesn’t even get into the 4’s.

I am now pursuing a private endocrinologist but I haven’t told my NHS Endo. Why would he need to refer me? He is just passing me on so he doesn’t have to deal with me?

I was referred in Nov, I was seen on 14th February (Happy Fecking Valetines Day 😩) and now he wants to pass me along?? I think it’s really appalling!!

[SlowDragon Administrator]

They haven't dismissed it as irrelevant....just stalling

One NHS centre in Kent is now offering DIO2 gene test to patients struggling on Levothyroxine and NHS T3 prescription if test positive

Other areas are accepting private DIO2 gene results. Sometimes very reluctantly

Some CCG areas still trying to give blanket refusals to any T3 requests

[MaisieGray]

There is no standard response as it is still fairly early days in the use of genetic testing for the diagnosis or treatment of thyroid dysfunction issues, and these particular common variants in particular. My two Endos accepted my own Regenerus homozygous-positive test result; but clearly have sufficient understanding to feel comfortable doing so. So I think it's great that your Endo recognises his lack of expertise in the field - he could easily have dismissed your results out of hand, as some others do - but I also think that his decision to refer you to a genetic clinic is OTT and unneccessary. I would have thought he could have a 10 minute telephone conversation with someone there, which would adequately inform any decision he might wish to make about adding Liothyronine to your Levo, or not.

But looking at your results, your TSH is perhaps higher than might be right, for you to feel well, and indeed, at 16.8 your FT4 is only marginally about the midway point of 16.5 with that reference range. So irrespective of any T4:T3 conversion issues, you appear under-medicated at present, so your FT3 doesn't stand much of a chance to be optimal.

[NWA6 in reply to MaisieGray]

Thank you MaiseGray 😀 I think you have given me a more positive perspective on my Endo, you’re right he may recognise his lack of understanding of this test and so yes ofcourse I would rather he is guided. However as you said I think it’s OTT that he’ll refer me to a ‘Genetic clinic’

[jimh111]

You seem simply undermedicated. Do you have results from when your fT4 was above e.g. 20? The DIO2 polymorphism has a small effect, if you acquire it from both parents, it lowers fT3 by about 0.4 so wouldn't make a great deal of difference.

[NWA6 in reply to jimh111]

Do you know for sure that a faulty gene from both parents would have minimal impact? I only have one from one parent so from what you state then I wouldn’t need T3 at all? I have tried to raise my T4 it lowers my TSH but doesn’t completely take away symptoms it just makes life easier to soldier on and push through the symptoms.

I think I have my history in my profile if you’d like to look? If it’s not there or not readable I’ll type it in this post 😀

[jimh111 in reply to NWA6]

The original research academic.oup.com/jcem/artic... found that patients homozygous for the rs225014 polymorphism of the DIO2 gene didn't do quite so well on levothyroxine only therapy and responded to combined levothyroxine / liothronine treatment. A slight flaw in this study is that they replaced 50 mcg L-T4 with 10 mcg L-T3, 15 mcg L-T3 would have been better.

I don't think the DIO2 polymorphism matters much. 1. Because the diffence in symptoms is not much, certainly much less that what many patients experience. 2. Logically if we provide sufficient L-T3 to replace the T3 secreted from the thyroid plus the T4 converted to T3 by the thyroid then the patients should be fully restored to how they were before they became ill. At a guess I would have thought 10 mcg L-T3 would be enough. Many patients do not get better on this low dose of L-T3, therefore my judgement is that their need for L-T3 is due to different reasons.

So, just because you have the polymorphism from one parent it doesn't mean you don't need L-T3, it just means the reason for needing L-T3 is probably not due to the DIO2 polymorphism. In your case I would bring your fT4 up a bit and see how you do, you've said it helps a bit. In which case the logical approach (the logical approach not the endocrinologist approach) is to give you some L-T3 and see how you respond. I think the endos have got their science back to front. They put forward hypotheses and demand that patients respond accordingly. What they should do is carry out an L-T3 trial to see what hormone levels optimise your response and then try to figure out what is going on. The theory / hypothesis has to comply with the experimental data, not the other way around.

So, you may well need L-T3, it's just my view that it's not because you are heterozygous for the rs225014 polymorphism.

[NWA6 in reply to jimh111]

Sorry jimh111 you lost me with the science. I don’t know if it’s because you’re trying to be purely scientific but statements such as ‘I don’t think the DIO2 polymorphism matters much 1. Because the difference in symptoms is not much,certainly much less that what many patients experience.’ Are not really helpful unless you DO know why a person would need to add T3?

Did you look over my history of blood tests? I have always pushed for more T4 but in Summer last year I was experiencing Hyper symptoms. More T4 does not seem to work for me.

[SlowDragon Administrator in reply to jimh111]

This genetic variation wether homozygous or Heterozygous, adding small dose of T3 can make vast difference for some of us

I am only Heterozygous, but adding tiny dose of T3 was a miracle

The low FT3 is not visible in the blood test resting

thyroiduk.org.uk/tuk/testin...

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.

[jimh111 in reply to SlowDragon]

That's very interesting. If a patient responds to a small dose of L-T3 (e.g. <= 10 mcg) then it is consistent with the polymorphism having an effect. Also, it's always possible that you have another polymorphism that nobody knows about and this has a greater impact - the Panicker study only looked at 'common polymorphisms'.

The quote you give '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.' is slightly misleading. It's true that the blood test will not show the full effect of the polymorphism (one study did find fT3 was about 0.4 lower but the Panicker study found no difference). However, we should remember that subjects with the polymorphism are generally OK until they become hypothyroid. We have to be careful not to give the false impression that these patients have a problem with the T3 levels within their cells, they are designed to work this way, once their serum fT3 is brought back to normal the polymorphism is not relevant.

The reason I'm pedantic on this issue is that patients may place too much reliance on this polymorphism, waste money on genetic testing or wrongly believe they don't need T3 treatment if they don't have the polymorphism. However, many patients have been able to get liothyronine prescriptions because they have the polymorphism, whilst this may not be the true reason they need L-T3 I wouldn't refuse a prescription on this basis!

(The link to the study on the Thyroid UK page doen't work, this one works academic.oup.com/jcem/artic... ).

[NWA6 in reply to jimh111]

Sorry I don’t know your history jimh111 and whilst it is evident that you enjoy your science I don’t think it’s helpful, it’s almost as bad as the Drs we have to deal with. They don’t understand why we don’t fit in their scientific box and so they won’t offer treatment. We need to get back to ‘how do you feel?’ In order to treat patients, if scientists what to keep going to find answers fabulous! But they need to stop denying treatment just because they don’t yet fully understand how it works.

But also, yes I agree with your statement that it’s not fair that someone with a positive result could get T3 but others without can’t, that is unfair but I for one am pleased with my result even if I don’t understand it fully, if I get T3 I’ll let you know just how big (or not) and influence it is on my symptoms 😬

[SlowDragon Administrator in reply to jimh111]

Well the wider Blue Horizon DNA test looks at other possible issues

thyroiduk.org.uk/tuk/treatm...

I am waiting for price to drop to the previous offer price of £99 to see if I have any other DNA issues

But yes....my endo added 2 x 5mcg initially. This resulted in almost complete transformation, Dramatic improvement within days

After blood test 6-8 weeks later (and confirmation of Heterozygous DIO2) dose was increased to 20mcg - 1 x 10mcg, 2 x 5mcg T3. After experimenting.....3 x per day - 8 hour gap between each dose works best

[NWA6 in reply to SlowDragon]

Sorry SlowDragon was that link the right one? I didn’t read anything about Blue Horizon. Fab news about your endo and the results of adding T3. I am just waiting and waiting and being as patient as I can 😬

[SlowDragon Administrator in reply to NWA6]

Sorry

Here it is

Previously on offer at £99

bluehorizonmedicals.co.uk/t...

[NWA6 in reply to SlowDragon]

Wow! Now that looks like a test I could get behind! I’m so curious about genetics (don’t really understand the science but 🤷‍♀️) when was the last offer on?

[SlowDragon Administrator in reply to NWA6]

The run up to Christmas.

They were offering all three bundles for £199

bluehorizonmedicals.co.uk/d...

Actually these are on a pretty good offer now at £339

[jimh111 in reply to SlowDragon]

From what I remember the other polymorphisms don’t have any link to symptoms, although companies marketing tests always give vague references to studies. In any event if the reason for needing T3 was due to a polymorphism you would only need to replace the T3 that used to come from your thyroid to be perfectly well. I think 10 mcg would more than cover this, enough to bring fT3 back to mid-interval. The fact that you and many other patients need more T3 suggests there is another reason for needing T3. I’d like to find out the reason but it’s more important that we are treated according to symptoms and clinical response.

[NWA6 in reply to jimh111]

Well jimh111 if you ever find out I’d love to know. But for now if the DIO2 test is being used as a way to allow’ us to get T3 then I’ll jump on that bandwagon. When I’m well I’ll continue to be of as much help to the cause as I can 😀

[SlowDragon Administrator in reply to jimh111]

Well I think I could manage perfectly well on slightly less

But the madness of only getting a tiny 20mcg tablet that has to be cut up. This means 1/4's is about the smallest reliable dose with careful cutting

I did start initially on 1/8th twice daily (a speck of dust)

Would be extremely interested in trying 5mcg tablets, then could cut these smaller

[jimh111 in reply to SlowDragon]

You could quarter and then dissolve as per the manufacturer's instructions. This is designed to waste the vastly over priced tablets but wasting a bit of a quarter tablet would be OK.

[SlowDragon Administrator in reply to jimh111]

Hopefully everyone ignores that dissolve in water instruction to throw away most of each ridiculously expensive pill

Could dissolve just 1/4 though

I am considering exploring the possibility of trying the 5mcg T3 tablets

healthunlocked.com/thyroidu...

[jimh111]

Paula, I think I might have looked in the wrong place for your history. Looking at a recent post you give these numbers: Jan -TSH - 2.5(0.3-5) FT4 - 23.3 ((9-24), FT3- 3.5 (3.5-6.5)

Feb - TSH -2.1, FT4- 16.8, FT3- 3.9.

Clearly you were on sufficient levothyroxine in January and yet your fT3 seems low but your TSH still not low which is a bit unusual. Rarely this can happen in selenium deficiency - selenium is needed to convert T4 to T3 and if it is low the pituitary has impaired conversion and so fails to respond sufficiently to T4. If you haven't tried it I would try supplementing with selenium for a while. It is a long chance but in your case worth a try.

Assuming the selenium makes no difference I would agree you need some T3. I don't believe it is due to the polymorphism but as you say this is just the science. It's wrong to say we have to know WHY a person needs T3 before we can suggest it is needed. There are probably hundreds of examples in medicine where we know a treatment works without knowing why. It's this insistence that the reason is known before a prescription can be written which has destroyed so many hypothyroid patients' lives. Doctors should prescribe what makes the patient better and then sort out the science and reasons at leisure.

[NWA6 in reply to jimh111]

The numbers are not behaving jimh111! My dose hasn’t changed from Nov 2018 - March 2019.

On 12th March I managed to wangle another 25mcg out of a new GP (I binned the old one)So I have increased my weekly total slightly. Going back up to 150 x5 and 175x2

NHS endo is taking so long to deliberate on T3 that I just felt I had to do something. So I thought I’d do it slowly. It’s just a shame that I have no FT3 results from the time period when I was on 175mcg daily.

What I don’t think the Drs understand is that this is auto immune and even if I balance my meds and my nutrients and my diet, environmental factors can trigger a Hypo/Hyper again.

Instead the reception for me is that my numbers don’t ring true and so I must be a non compliant patient who’s washed their meds down with a gallon of Coffee in the morning 😩 It just galls me that I’m treated like a child and not believed either.

Thank you for not bamboozling me with science, I only gained a C in GCSE Biology, that’s enough for the basics, anymore and I’m out 😬

[NWA6 in reply to jimh111]

I meant to say that I felt at my worst in Jan and early Feb 😬 And I’ve always taken Selenium with my meds for 3/4yrs now.

[jimh111 in reply to NWA6]

So selenium deficiency is definitely not a problem. You need to persuade your doctor to prescribe liothyronine. You could point out your fT3 is continually low, or maybe mentioning the polymorphism might help (even if from a scientific view it doesn’t make sense). If they suggest you are non-compliant I’d bite their ear off, in autoimmune hypothyroidism thyroidal secretion can fluctuate with autoimmune flare ups.

[NWA6 in reply to jimh111]

I have been fighting for 10yrs! If you look at my previous post I’ve also got my referral letter from my GP. She has lied and not painted a good picture of me as a patient. It was after this letter and the fact that she got my pharmacist to ambush me when I went to pick up my meds in Jan, well I couldn’t tolerate her any longer. Got myself a new GP and a new pharmacist! It just shouldn’t be this hard! It’s 2019 FFS 😩

I am just in the process of being referred to a private endo who has been recommended so I’m hopeful that I’ll be on T3 sooner rather than later. Meanwhile I’ll probably still be waiting on my NHS endo getting his act together 😩

[jimh111 in reply to NWA6]

So sorry, I know how difficult it is to fight when you are hypo. I just looked at your 10 yr History post, I misunderstood what you meant by your ‘history’. Your July 2016 result is weird, your TSH should have been much higher. This suggests your pituitary is not producing enough TSH. This can affect your conversion. Another issue is that your blood test results are all over the place. I don’t mean the numbers, we can swing from hypo to hyper, but in your case the relationship between TSH and fT3, fT4 is very inconsistent. This cannot be explained by non- compliance. I guess it’s just possible the assay is subject to interference, this does happen sometimes when the patient’s antibodies interfere with the assay. They could spend an awful long time trying to work out why you have strange results but the best approach is to try you on liothyronine.

[NWA6 in reply to jimh111]

Thanks jimh111. It helps to have fresh eyes look over things. I certainly don’t understand what’s going on. It took me a long time to get that all written down and I’d do a spreadsheet if I knew how 😬 I only just applied to see my records on line (funny to see my femur fracture from 1982 on there! 😂) but that has been my life saver esp after the lies my GP has told. My 10yr history clearly shows that the GP’s have prescribed me an increase in dose far more times than I have insisted I get one! And I was the one who decreased my dose as soon as I felt Hyper and yet my GP claims in her letter that she warned me and she also claims that when I had a TSH of 0.09 I asked for an increase! Another lie, I basically said what is going on? She said I dunno and I said you can’t leave me to live like this. She has obviously interpreted that in her own way!

I’d make a more formal complaint if I thought it would go any good but the Surgery is already not treating me very well so I have to tiptoe otherwise I risk not having a GP at all!! 😩

Roll on private endo maybe he’ll do more investigating.

This is familial for me, mum and NaN both ‘underactive’ never used the words autoimmune and sister with Graves. My eldest (17) is exhibiting signs of either Hashimotos or nutrient deficiency. I need to get well so I can get her sorted too.