Hi hope someone can clarify my query. If I have dio2 variant wouldn't my brain have always been deprived of t3 so why now am I aware? Also if I have always had variant what caused my tsh to raise if variant didn't on its own.
Dio2/changes in tsh: Hi hope someone can clarify... - Thyroid UK
Dio2/changes in tsh
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Timbutdim
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Maybe because before the body compensated by making more T4 to keep ft3 at a workable level and now your thyroid is no longer able to make the high level of T4.
Oh can t3 be created with the variant dio2 from T4 ? Sorry I thought the gland only released T4 and the brain needs t3 so was under the impression that no amount of T4 would make any difference on brain function
Normal functioning thyroid makes approx 80% of Ft4 and 20% of Ft3
Obviously if on just levothyroxine, which is only Ft4…..this can cause issues right away….or often issues get worse the longer you are on replacement thyroid hormones
I once read when taking synthetic T4 that our bodies then allow the synthetic version to supply all demands and our bodies stop producing and hence with variant no T3 for brain functioning I can not believe that the nhs don't screen for variants prior to administration of T4. Crazy
Yes, in effect, once you start on levothyroxine, TSH drops and own thyroid output ceases or significantly reduces, so you become entirely reliant on levothyroxine
Conversion of Ft4 to Ft3 requires OPTIMAL Vitamin levels, good gut function (gluten and/or dairy intolerance extremely common)
Conversion often gets worse after menopause too
Rare to find any endocrinologist who’s heard of Dio2 and only one CCG area recognises it
Ignorance would not be justified within the courts of law If they were behind the wheel of a car they would be done for wreck less endangerment Neglect
Hi slowdragon ❤️
Was at A&E again yesterday with a resting heart rate of 147..bad muscletwitches/spasms, server headache and feeling sick.. First it looks like my calcium has gone up again from 2.53 in March to yesterday at A&E it was 2.59....i explained about hyperparathyroidism needn't have wasted the little energy I had, he really didn't want to comply... He left the room and came bk saying he'd looked bk on my last thyroid bloods, he came bk with the same answer the last doctor did just 2 months ago when I was at A&E with a resting heart rate of 133..he says its over medication of T3 probably toxicity 🤷♀️... I don't get it slowdragon, my last thyroid bloods were..... T3..... 5.9....range 3.10...6.80)....T4..2...range.. 11.00...22.00)......TSH....0.05....range.. 0.30...4.50)......on the blood draw the 14th June 2021...i was having pth, calcium ect he had popped a thyroid one in without me knowing of course I took my meds as usual 20mg...10mg at 8am.. 10mg at 2pm.....blood draw. 3.35.....results were.... T3.. 11.3....TSH.... 0.04....no T4 done... Can I ask you do you think I'm over medicated with toxicity 🤷♀️..... He sent my A&E bloods off to carslile hospital to have another full thyroid pannle done was supposed to get the results yesterday but he never called me bk.. 🙄
How much T3 are you currently taking
Do you currently split the dose ….how often and what doses
You might need beta blocker to regulate heart rate
What vitamin supplements are you currently taking
Have you gone strictly gluten free
Hi slowdragon 💗I was taking 30mg..t3..i was just about to increase to 35mg..as I said I was doing good getting out sleeping better, then about 5/6 weeks ago my heart rate went to 133 resting..with muscle jerks/spasms /tremors.. Sweating server bad head.. Yesterday it was 147 resting in A&E... Same symptoms as above..
You already know my struggle with the symptoms of hyperparathiyroidism, these are the symptoms, fast heartbeat, muscle spasms jerking sweating bad headaches ect are associated with hyperparathiyroidism,
I take my T3 in 3 split doses... 10mg 8am..10mg..2pm..5mg 8pm...you will note the drop from 30mg to 25mg as the doctor in A&E the first time said its over medication of T3... So I dropped 5mg down to see if it made a difference, But obviously its not changed anything in A&E again, I'm sure I've been on this T3 (lactose free teva) for 11 months..with NO problems, it has only been the rise in calcium & pth that has caused the symptoms, again my calcium as risen, from 2.35....2.53....now 2.59...in hyperparathiyroidism the parathyroid glands go over and send a signal to dump calcium from the bones in to the blood causing a raised calcium level, my pth has also risen again from 4.4 to 5.3...so if you put all the pieces together the only thing I can come up with is my parathyroid glands are not acting normally, surely if it was T3 toxicity I would have known with in a few months of being on the T3.. Not within 11months..and would it not show on my blood work I was toxic slowdragon, anyway a bit of good news I'm hoping to see a endo so can ask about this T3 thing.. 💗💗
Personally I had to be on beta blockers for years to stop dramatic heart rate changes
But absolutely strictly gluten free diet was astounding improvement…..and all vitamins optimal
Hi
Yes I appear to have vits OK.. But my magnesium is.. 0.76) ..range.. 0.70..1.00.. This was noted by a parathyroid member on the parathyroid site, apparently low magnesium is part of hyperparathiyroidism, also kidney function can be affected by hyperparathiyroidism, my eGFRcreat, is 64...ranges.. 90.00..120.00)..creatinine 86..ranges.. 49.00..90.00 this was 99 last month.. Vitamin D is 54...but Ive been told not to take vitamin D as my calcium is raising up then down.. (indicative of hyperparathiyroidism) if you take vitamin D it raises Yr calcium even more.. I was on vit D from Nov last year to Jan my calcium we nt to 2.68...im not gluten free.. I don't eat bread, don't drink coffee, don't add sugar to anything, or salt.. I'm dairy free (lactose).. I try so much to watch my diet.. I really don't think all this has anything to do with my thyroid meds or thyroid health.. All my bloods point to hyperparathiyroidism.. Still urinating loads still very thirsty, bad heads everyday, sweating, shaking, just very unwell and bk to being bedridden again... Never thought after my thyroidectomy I'd be back to this life of hell... 😢😢😢😢
People with the DIO2 polymorphism convert slightly less T4 to T3 and get more T3 from the blood. If their thyroid packs in they don't do quite so well on levothyroxine monotherapy. There's been no evidence that those with the polymorphism have impaired brain function of any kind.
Jim (haven't a clue whether I have the polymorphism).
I have it. My brain is fine. It's my body that's screwed. No energy to do normal things like go for a walk to do the housework other than in short bursts.
The brain is the brains of everything we do without our brains we are not going to achieve our goals
What I mean is that my brain is functioning well. I'm reasonably intelligent and quick witted and keen to learn new things. But my legs won't go.
I don't think they can use the dio2 protein as a precursor to many brain degenerative diseases but as far as I'm aware the synthetic T4 does not convert to T3 with the dio2 variant and so can cause retardation, dimentia and other hypothyroid symptoms
Like many members with heterozygous DIO2 I have seen significant improvement on levothyroxine plus T3 prescribed alongside
Gluten intolerance is more likely cause of brain fog and being absolutely strictly gluten free can slowly improve brain fog issues
For me the correct medication at the correct dose will give good brain functioning for the dio2 variant all additional good health practacises will bring benefits of a different kind.
Synthetic L-T4 is the same as thyroid all T4. The DIO2 polymorphism has a minor effect on deiodinase (T4 to T3 conversion. Going from memory one study found no difference in fT3 levels between subjects without the polymorphism and those who had inherited it from both parents. Another study found fT3 was 0.4 lower in those with the polymorphism from both parents.
Everyone can convert T4 to T3 but those with the polymorphism convert a little less and this shows up as minor cognitive impairment in patients on levothyroxine monotheraphy. Although real it’s important not to exaggerate the effect of the polymorphism because it would condemn those who do not have it, or have inherited it from one parent to being denied T3 treatment.
Do you have a link to the study or who did the study and if the study was on humans or rats Also living with that minor cognitive impairment has isolated people from normal social interactions and isolated people from there families so yes I can see it's minor issue for those not affected
It also doesn't advise of the degree of impairment. Because genes interact with other genes , one person's x amount of mutation on paper might be felt more severely than another with the same impairment. Also other health conditions will influence as in epigenetics.
As I understand it DIO2 polymorphism affected peripheral conversion of T4 toT3 in the tissues such as the brain. A study looking at serum T3 levels would not pick this up as serum T3 is produced also by DIO1. Was the study you were referring to looking at serum T3 or T3 in the tissues?
What's serum T3 in the study's and T3 in the brain Sorry I don't know could you explain
Serum T3 is the level of T3 in the blood, either total or free. The issue for some people is that some tissues rely on locally produced conversion of T4 to T3 and it is not clear that T3 or T4 levels in the blood reflect what is going on in the tissues in the brain, liver and skeletal muscle.
Just wondering if serum T3 or T4 via medication is the problem I'm thinking if blood levels are high maybe it turns off the mechanism for the localised conversion as maybe TSH is too low to trigger response I was on Hrt which oral tablet which was not recommended with levothyroxine therapy as they share the same protein vectors or transport vehicles to get inside the cells well after a few months on Hrt my TSH was 24 and was told by nurse at go practise no Levi increases needed despite TSH levels nurses are specialists now lol Anyway I looked like I had been dragged through a hedge backwards as my T4 lost the protein race but mentally I felt extremely well Much better than when my TSH was low
My reply to Timbutdim radd Mollyfan
This is the original study that found minor cognitive impairments in patients on levothyroxine monotherapy who inherited the polymorphism from both parents academic.oup.com/jcem/artic... . These are small effects on mood and cognitive abilty e.g. being able to meorise six numbers in reverse sequence. These effects would be fully compensated by taking sufficient liothyronine to replace the six or seven mcg T3 normally secreted by the thyroid.
The above study and at least one other found the polymorphism made no difference to the effect of levothyroxine monotherapy on fT3 levels. i.e. fT3 was reduced to the same extent if you had the polymorphism from both, one or zero parents. One study found that fT3 was reduced by a small amount (<+ 0.4 pg/ml), see Figure 1 C, D in academic.oup.com/jcem/artic... . This study looked at patients who had their thyroid surgically removed, patients with some remaining thyroid tissue would have smaller effects.
It's important to understand that the polymorphism only matters when someone becomes hypothyroid, when they lose the small amount of T3 secreted by the thyroid. This loss of T3 requires higher T4 doses to normalise fT3 which lowers TSH and affects brain D2 activity. Giving a small amount of L-T3 (<= 10 mcg) should fully compensate for the loss of thyroidal T3 and eliminate the effect.
Many patients have a weakened thyroid axis with low normal TSH, fT3 and fT4. Their fT3 may be reduced from e.g 5.0 to 3.6 or even lower whereas those with the polymorphism would have an fT3 reduced from e.g. 5.0 to 4.6. Thus, the polymorphism does not explain fT3s well below average and does not cause severe problems, the Panicker study was only just able to identify cognitive problems.
Indeed those with the polymorphism are at a distince advantage - provided they can be prescribed a small dose of L-T3. The reason is that this group are adapted to get more T3 from the blood than from type-2 deiodinase (D2). Those without the polymorphism are more dependent upon D2 and will be affected to a greater extent if they suffer any conversion problem.
jimh111,
Thank you for the explanation.
With regards to your last paragraph you cite those with the heterozygous polymorphism are at an advantage (as long as they can medicate T3), thus indicating those without the polymorphism are disadvantaged.
I don’t understand why this would be as even with the limited conversion abilities by the D2 enzyme that a low/suppressed TSH induces, surely with all the other multifactorial hypo conditions that likely impair D1 conversion, do the bloods not look similar? Also after years of being undiagnosed it must be possible to have a weakened/blunted thyroid axis alongside the polymorphism?
Am I looking at this wrong?
The effects of the polymorphism are minor but it is an example that proves at least some patients need T3 to fully recover. Those without the polymorphism are slightly more reliant on D2 generated T3 and so are likely to be slightly worse off if they have poor conversion. The essential point I'm making is that in my view the polymorphism isn't important provided those who have inherited it from both parents get a little T3.
The danger is twofold. 1. That patients who are not homozygous for the polymorphism are denied T3. 2. That we pay too much attention to the polymorphism when other causes of impaired T4 to T3 conversion have much greater effects. Apart from enabling some patients to get liothyronine the polymorphism isn't very important, it only reduces fT3 a little and has minor effects. The cause of more severely impaired T4 to T3 conversion and severe hypothyroid effects lies elsewhere.
Thanks for the link was a bit much to digest for a non acedemic but interesting all the same
So what I think you are saying is that mono T4 therapy regardless of dio2 variant will also for reasons unknown require T3 in order for the patients to feel well
Yes, there can be a number of reasons patients need T3 often at higher doses and I feel these have greater impact than the DIO2 polymorphism.
Timbutdim,
I think it depends on the degree of the variant and how long you were left deficient.
My brain was always slowed and brain fog was awful, and then suddenly cleared after adding T3 to my T4, whilst I suffered weird pops and effervescent bubbles in my head for the next two years or so. And yet now conversely I need very little T3 in my meds in spite of being totally replacement dependant and having the variant.
When I was first introduced to T4 I felt like an alien and didn't get on with it at all from mental health perspective Looking back it felt to me a none medically trained being that the T4 may have stopped my own thyroid producing /supplying thyroid hormones, although struggling to meet demands at that increased period of stress, to my body. I believe that T4 in its natural none synthetic way can be converted to to T3 and used by the brain for mental purposes. I believe that having the variant which I may have may deprive the brain from full cognitive functioning when when given only synthetic T4. I can understand that the increased stress period I was going through prior to diagnosis would have put extra demands on my adrenals but why wouldn't I be diagnosed with addisons rather than auto immune hypothyroid as stress I thought as in environmental stress passes and once passed my adrenals would cope and hence surely TSH would return to normal???
Timbutdim,
Because the stress on your adrenals wasn’t enough to fully shut down cortisol production and the trouble with the existing practice is if you are 1 point above the range that denotes Addisons you will receive no help or medication with regards to your adrenal health.
Yes …. ‘that having the variant which I may have may deprive the brain from full cognitive functioning when when given only synthetic T4’, it felt it was slowly & insidiously poisoning me. The brain needs loads of T3. There are more T3 receptors in the brain than anywhere else in the body and T3 can also be produced by neurons as well as being a hormone.
T3 also causes massive neuotransmittor imbalances, hence the intense feelings of joy or depression. It is used in the medication for chronic depression & bi-polar. Serotonin is heavily influenced by thyroid hormones, hence some members successfully supplement 5- HTP. It didn’t make any difference to me. And others suffer the consequence of SSRI’s as ironically many studies have shown AD’s to be only effective when thyroid hormones are optimal!!
I recently have investigated RLS after many sleepless nights and there is fairly strong evidence of some dopaminergic system imbalance with thyroid hormones. And iron is huge in production of both serotonin & dopamine (& I have iron-overload!) whilst low thyroid hormone creates the cortisol issues that result in low stomach acid and inadequate absorption.
Glucose is also necessary for GABA (and for T3 to enter cells), yet the cortisol issues commonly seen with low thyroid hormone will result in blood sugar issues. Place the DIO2 variant into the mix and sometimes every which way we turn there is another obstacle 😳😆.
As for the serotonin I tried intense dark chocolate but then my cholesterol rocketed lol but yes I felt numb and void of feeling emotion or connected to anything or anyone I tried ginkgo ubiquinol maca ashwagandha anti psychotics just didn't feel like me
Yes my blood sugars were borderline so took chromium
And yes always another obsticle how very true
Dont I know it. My endo point blank refuses to let me have T3 only and suggests I add NDT to bring up the T4 from 0.05.I have suppressed TSH which did rise slightly to 0.12 from 0.3 but FT4 did not move whilst on 1.5 NDT and 30mcg T3! He has been consistently dropping my T3 (which I buy myself) so much so that FT3 was 4 points from bottomof rang and I felt rotten!
I recently had a private ultrasound done and I have very small thyroid with lobes measuring 2cm! I have 1 polymorphism to the dio2 gene just to compound matters. He has now upped my T3 back up to 40mcg and suggested 1 grain NDT since I donttolerate levo! He tells me and the surgery I have clinical need and then says no way will I get T3 on the NHS. Surgery say I wont get it in clinical practice and we are in dispute!
I think Ive been well and truly stitched up between the endo and surgery! Im left with no choice but to go it alone!
Janexx😒🤓❤
JaneChapple,
Sorry to hear this. It is a similar story for many members hence the size of the forum, and we self-medicate. This is far from ideal but essential in retaining some degree of wellbeing.
I don't understand why your endo is so influential in your dosing if you are buying meds yourself. Also many of us have a low TSH because we are medicating T3. If you wish to discuss your story further or pose a question, write a new post for members to comment.
Welcome to the forum, Timbutdim.
I’m wondering what’s behind your question. If you’re still suffering brain fog, what are your thyroid blood levels looking like? I see from your profile you say they’re “normal”. That doesn’t often mean optimal for you.
I'm just returning my tsh to within range after being on another hormone which sent my tsh to 24 I'm usually ok with brain until tsh very low?? Funny brain felt OK at tsh 24
Hmmm. Interesting.
When you say “in range”, what kind of number are we talking about? Many people being treated for hypothyroidism don’t do well until TSH is less than 2 and often under 1.
Also, what are your Free’s doing- FT4 and FT3? Is your doctor even monitoring those? These are your active hormones. TSH only stimulates their production and, when on Levothyroxine are a less good indicator of what is going on.
I know that my brain fog didn’t clear until I got both my frees in a reasonable place, and it comes back, if for any reason things go awry.
Well I say range usually on 125mcg T4 daily with no contraindications or break in taking them my TSH usually at 0.0 and at that point I feel nuts, totally nuts and I still get symptoms of under medicated like constipation dry skin hair fatigue I just can not tolerate my TSH that low as I feel constantly twitchy and unsettled and being in public places is like being in hell If I take less T4 I can not open my bowels and struggle to get out of bed i seem to be doomed either way . Last check my TSH was 6 and my brain still feels good I will know when it gets to the 0.0 again without any need for bloods as visually I look like a nut case on crack with creepy none reactive eyes enough to scare the bejesus out the grandkids and myself for that matter lol
I don't understand the mechanism, but have you had your RT3 tested? If you can't convert T4 very well, I understand that it can become RT3, which makes you feel rotten with all the normal hypo symptoms, regardless of FT4 etc.
Have you heard of Paul Robinson? He has written extensively about the thyroid and particularly T3.
I decided to medicate myself as I was severely unwell some years ago (and found the endo that I saw privately unhelpful...my TSH was 3.8 and they wouldn't treat me until it was 5...despite me having all the symptoms so badly that I couldn't function and also having very high antibody levels) and ended up feeling much better on T3....but I wish I had read Paul's books before I embarked on that!
Don't think I've ever had results for rT3 not sure they check that I did read that rt3 and testosterone are connected some how???i think of you have too much rt3 it converts to testosterone blimey that would cause roid rage surely Funny a friend did say they are going to turn you into a man I thought he was joking lol
No I haven't heard of Paul Robinson is he also a fellow thyroid sufferer??
I also self medicate as I have heard about that rt3 so I take ashwagandha and I feel much better approx 30 after taking it Have you tried ashwagandha for rt3 or increased testosterone
I have never had my rt3 tested, but I take T3 only. Paul Robinson was a fellow thyroid sufferer who did a lot of research and worked with some very talented endocrinologists and now explains how he got better.
You can get private blood tests...I know Blue Horizon do a lot of Thyroid blood tests and they may offer RT3.
As for Testosterone, I am female, but I know that despite supplementing with testosterone mine is low
🙄
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