Deiodinising enzyme genetic deficiency and T3

Deiodinase DI02 test result positive. Does any one know what is a typical Thyroxine / T3 dose or ratio when I have received the faulty gene from only one parent, eaning I have reduced ability to convert T4 to T3.

I have been hypothyroid for several years. Formally diagnosed only last December and put on 75mcg levothyroxine and 10mcg T3 for three months which was clearly not enough. Persuaded my GP to increase to 15T3 but after a month this is still not enough. Prior to my NHS diagnosis I had been self medicating with T3 at 37mcg per day and was functioning well. ( I am giving the NHS one last chance, before going my own way again with NDT plus T3 or maybe even back to T3 only )

Any advice or experiences much appreciated as my GP hasn't any idea about how to respond to the DI02 test result and my endo at Addenbrooks was totally happy to leave me unwell on 75/10 for another FOUR MONTH period.

Thank you - Andi

34 Replies

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  • AndiRiley,

    If you post your recent thyroid results and ranges members will advise whether you are optimally medicated. There is no typical combined dose, people need what they need. Adding T3 to T4 overcomes poor conversion. Most people will feel well with TSH <1.0 and FT3 towards, or in, the top third of range.

    1 grain (60-65mg) NDT contains 38mcg T4 and 9mcg T3. You may not need additional T3.

    __________________________________________________________________________________________

    I am not a medical professional and this information is not intended to be a substitute for medical guidance from your own doctor. Please check with your personal physician before applying any of these suggestions.

  • My labs ( I was feeling "not good at all" ) on 75T4 and 10T3 were: 0.34 ( 0.35 - 5.50 ) FT4 12.2 ( 10.0 - 19.8 ) FT3 4.5 ( 3.5 - 6.5 ) Ferritin 45 ( 22 - 275 private test ) Reverse T3 ( low normal - private test ) I have supplemented with 200mg pre day elemental iron for five weeks and have taken ten days off- and I am about to retest ferritin - I expect it to have improved!

    I am finding that on 20mcg T3 ( + 75 T4 ) I have largely regained my functionality and have VERY much reduced symptoms. I don't yet have any labs, and my GP thinks I'm on 15T3, endo thinks I'm on 10T3.

    I have Thiroyd NDT and tried this for a week, not sure it is "good stuff" so I have reverted to Levothyroxin and T3 to tinker with timings simply because I know what's in the tablets. I really need to fix this waking with strong symptoms between 3:30 and 5am every night or needing to go to bed for an hour every afternoon.

    Thank you Clutter.

  • AndiRiley,

    20mcg T3 probably lifts your FT3 close to top of the range and that's why you feel better.

    It usually takes months of supplementing iron to optimise ferritin. Taking iron with 500mg-1,000mg vitamin C aids absorption and minimises constipation.

    1 grain (60-65mg) Thiroyd contains 38mcg T4 and 9mcg T3 so 2 grains is almost equivalent to 75mcg T4 + 20mcg T3. Dividing T3 dose x 2 can help avoid the afternoon slump.

    _________________________________________________________________________

    I am not a medical professional and this information is not intended to be a substitute for medical guidance from your own doctor. Please check with your personal physician before applying any of these suggestions.

  • Thank you. Next problem is how do I get GP and/or endo to see it this way? Endo at Addenbrooks was not happy that my GP was considering moving me up for 10T3 to 15. Endo Prof C* was thinking about reducing my dose because TSH is below range. Do I really have to go my own way as I have done for the last several years before they finally accepted that I am hypo when my TSH finally got to 10.4.

    * Edited in accordance with guideline #25.

  • AndiRiley,

    Try telling your endo that you feel well on 75+20 and want to stay on it.

    My endo is trying to raise my TSH from <0.01 "to protect my bone health". I don't believe suppressed TSH secondary to thyroid replacement is damaging. 2 dose reductions haven't budged it but the 2nd dose reduction, although small, increased my fatigue and made me feel cold. I refused to further reduce dose and told her I prefer to feel well today and accept that might increase the risk of future adverse health outcomes. I also said I would buy on the internet if she changed my prescription. She has left my prescription as it is and will see me in clinic in 2017.

  • Good luck. I am planning on trying the same approach with the back up plan of NDT and T3 from planet internet. I might still do that anyway, but I want an "official" prescription and supply because of the current and potential unreliability of supply from the internet drug shops. I had some T3 from NL pharmacy which turned up wrapped in tomato ketchup sachets and only contained a third of what I'd ordered. The tablets were a dirty yellow colour. Who knows what the hell they contained.

    Thank you for sharing your thoughts.

  • AndiRiley,

    When you want to buy T3 from the internet post a question asking members to send you sources via private messages. I've not heard complaints about short or non-delivery from any of the recommended sources.

    Dirty yellow colour T3 sounds like Uni-Pharma which is popular with members.

    I've not heard of that pharmacy. I've edited your post to comply with guidelines which don't allow sources to be posted on the forum.

  • Sorry - didn't know about non-disclosure of sources. I would certainly not use them again - they tried a hard sell on my mobile for a couple of years afterwards repeatedly on a range of drugs.

  • Andi,

    Your results TSH 0.34 ( 0.35 - 5.50 ) FT4 12.2 ( 10.0 - 19.8 ) FT3 4.5 ( 3.5 - 6.5 ) show that your TSH is rather too low for the low fT3, fT4.

    Although not proved with certainty yet there is evidence that TSH promotes peripheral T4 to T3 conversion. Thus if your TSH is under responsive you will get less peripheral conversion. Hence, if they give you more L-T4 your TSH will drop further and hence you will convert less T4 to T3. The solution is to keep your L-T4 at 75 mcg for now and increase your L-T3 to 20 mcg (as you have done) preferable taken half at breakfast and half at bedtime.

    When you get your blood taken try to have it taken 8 to 12 hours after your last L-T3 dose. This will give a realistic approximation of your average fT3 levels. In your case as your TSH is not responding correctly it is of no use for monitoring your treatment.

  • THANK YOU. You have put into a succinct statement my exact thoughts. With TSH that low FT4 should be higher so the "control system" would seem to be broken. I have a similar mismatch of blood test results with sodium, potassium and aldosterone - they just don't fit the pattern of a functioning system.

    I deliberately didn't take my morning dose of T3 before my last 10:00am blood test at Addenbrooks because it seemed obvious good practice to me to not have a snapshot taken just after my dose. My endo was astonished that I had done this - it didn't seem to occur to him that the results would be skewed by doing a test two hours after ingestion. ( He is a professor fgs )

    I was actually considering reducing my levothyroxine to 50mcg and not telling him. my TSH might then get in range and he wouldn't be so keen to reduce my overall doses as he was at my last appointment in April.

    Tonight I am going to try taking my 75T4 and 10T3 at bedtime. With as you suggest 10T3 in the morning. If I get a bit hyper n the morning I will try 5 and 5 the following day.

    Thank you again jimh111

  • I hope the professor wasn't prof C, he is very smart and should know better. If you have the blood taken an hour or so after taking liothyronine you get an absurd fT3 figure as the liothyronine hasn't had time to bind to the transport proteins. Of course if you leave too long you get an unrealistically low fT3 due to the short half life of T3.

    TSH is useful for spotting primary hypothyroidism early, but only if the thyroid axis is working normally. It amazes me that doctors don't verify the axis looks reasonable before relying on a TSH figure.

    Your plan sounds good. I find the nighttime L-T3 is more important than the morning dose.

  • I have had my best day for ages. Worked like a Trojan all day, 4pm and still going. I had a disturbed night but for other reasons, hopefully not repeated tonight. I have a graph somewhere which shows that serum T3 is highest during the middle hours of the night, which would seem to backup your view that the nighttime dose is more important.

    Yes, it was Prof C. I was reasonably encouraged at my first appointment, but have been repeatedly disappointed by what I view as his school boy errors: not noticing that my GPs labs had a very different reference range when he was interpreting the results, which meant that he interpreted a 20th percentile FT4 as being above mid-range. He forgot, and needed prompting to re-test DHEA and testosterone despite both being below range and declining in consecutive tests.. Said that they "don't really pay much attention to FT3 levels anyway" Contradicted my GP, who said that given my continued symptoms, the blood test results allowed a "little wriggle room for increasing doses" Was inclined to reduce my dose because my TSH was below range. Left me on an unchanged dose for FOUR MORE MONTHS despite reporting "job losing symptoms" and an imminent employment tribunal. Paid no attention at all to my mid 40s basal pulse rate, my persistently low temperatures or the fact that I felt worse after three months on his medication regime than at any time for over a year. !

  • Oh dear. When I was the prof a good ten years ago he was pretty good. I get the impression that all endos have now agreed a standard response. He is one of the best specialist endocrinologists so it is really disapointing and doesn't say much for the rest. I would point out that your TSH is too low for the given fT3, fT4 and should not be relied upon. Maybe they could check your TSH response to TRH.

    Looking forward this team is trying to develop markers for thyroid hormone action. If this research is successful we will have indicators of how the patient is responding to thyroid hormone. This could kill off this TSH nonsense once and for all.

  • I will certainly put forward the suggestion about checking TSH response to TRH. Thank you.

    I wonder if you have any suggestions about how to get Prof C to support my continued use of twice as much T3 as he prescribed? 20mcg versus 10mcg ( My GP approved 15 and I need to see him soon to tell him I've started functioning like a pretty normal human being now I'm on 20 ) I do have graphs of symptoms scores, temperatures, pulse rates etc, but both my GP and Prof C get a glazed look in their eyes when I try to present them, and Prof C gets a scornful tone of voice and won't even look at them.

    Also worried about rumours that T3 is going to be unprescribable any way - is this true?

  • You are doing pretty well as you managed to understand my mistyped sentence 'When I was the prof'! I swapped the s and w in 'saw'.

    All you can do is reinforce the point that the 20 mcg L-T3 works. As a scientist he should be driven by the data (the patient response) and not existing theory. I would not mention the DIO2 polymorphism, it does not explain your need to 20 mcg which is way more than the polymorphism deprives you of. He really should pay attention to your symptoms and response to medication, this is how he manages his patients with resisitance to thyroid hormone (RTH).

    The most likely explanation for hypothyroidism in patients like us is endocrine disruption by environmental toxins (I'm not an enviromentalist nut). The Endocrine Society has endorsed this approach and published a very detailed statement which can be found on this page endocrine.org/endocrine-pre... . The detail doesn't matter, the fact is that thyroid hormone action is being disrupted by yet to be illucidated mechanisms. The UN and WHO have published similar statements. The point I'm making is that we do not undertstand thyroid hormone action sufficiently to take such a dogmatic approach.

    Many doctors are now dropping T3 prescriptions but others are starting prescribing. The official statistics show that the rate of prescribing has been fairly level over the last ten years or so. If anyone's prescription is dropped it is important to kick up a fuss.

  • Yes, I guessed you hadn't been involved in any body swap shenanigans :-)

  • The DIO2 polymorphism has very little effect, minor cognitive impairment when both genes affected. Thus the amount of T3 to correct will be very little. However, if you find T3 resolves your symptoms then it is likely to be due to some other cause. At least having the polymorphism allows your doctors to rationalise prescribing L-T3. It's sad that an endo at Addenbrooke's isn't helpful as this is one of the more advanced thyroid clinics. All I can suggest is that you keep a record of your symptoms and how they affect you and try and persuade the endo to give you more L-T3 based on symptoms not blood tests. An attempt to educate the endo.

  • Hi jimh111. Thank you for your reply. T3 often switches off my symptoms within an hour of taking it. Sunday I took all my T3 in the morning as an experiment, I had a great day and went to bed at 11pm - woke at 5:30am with palpitations, painful feet, knees, tight buttocks, aching back, freezing feet, low rectal temperature 36.3 and feeling very "quivery" ( all my usual symptoms). I took all my T4 and T3 meds, and within an hour everything settled, I went to sleep and woke at 9:30 feeling just fine - symptom scores at very low levels.

    Do you have any suggestions as to why T3 is so effective please? My TSH was suppressed to below ref range even before I increased T3 from 10 to 15 and now 20mcg. Thanks.

    My labs ( I was feeling "not good at all" ) on 75T4 and 10T3 were: 0.34 ( 0.35 - 5.50 ) FT4 12.2 ( 10.0 - 19.8 ) FT3 4.5 ( 3.5 - 6.5 ) Ferritin 45 ( 22 - 275 private test ) Reverse T3 ( low normal - private test ) I have supplemented with 200mg pre day elemental iron for five weeks and have taken ten days off- and I am about to retest ferritin - I expect it to have improved!

    I am finding that on 20mcg T3 ( + 75 T4 ) I have largely regained my functionality and have VERY much reduced symptoms. I don't yet have any labs, and my GP thinks I'm on 15T3, endo thinks I'm on 10T3.

  • I have a theory that if the TSH is lower than it should be then there is insufficient peripheral conversion of T4 to T3 as TSH tends to promote this. Hence these patients require more T3 than usual. TSH can be down-regulated it the patient has a period of hyperthyroidism, either due to taking too much hormone or from a period of unnoticed hyperthyroidism prior to hypothyroidism. Also certain conditions such as depression or strict dieting can lower T3.

    I would raise your levothyroxine, I don't think it will benefit you.

  • I agree that I have problems with peripheral conversion. The hypothalamus/pituitary system is geared only to guaranteeing ideal hormone levels within those glands.

    I don't understand your final sentence: I would raise your levothyroxine, I don't think it will benefit you. Could you clarify, or was there a typing error? Thanks.

  • Whoops! Would NOT raise levothyroxine. If you find you are still under medicated I'd increase the liothyronine.

  • Hi Jimh111

    I have the polymorphism and believe me that the effect of ndt compared to t4 alone is not an alleviation of a mild cognitive impairment it's the removal of a large large block to being able to think and function. I am heterozygous not homozygous.

    Everyone is different but me on t4 alone takes 2 days to put together a slightly complicated spreadsheet compared to me on ndt where I can put together a far more elegant solution to a complicated sheet in a day. My daily bread is earned from my ability to put together such calculations so this is a major issue for me

    My memory moves from one where I'm thinking of booking myself in for a test to see whether I have early onset dementia to one that's slightly scatty but normal for me.

    Ndt has been a lifesaver for my higher brain functions and dismissing the di02 gene defect as having very little effect and presenting as mild cognitive issues in those with a homozygous presentation is directly opposite to my experience. It probably is to a number of others on this forum. Given that we all react to different meds in different ways and that this forum is about helping people to find their own 'sweet spot' I'd suggest that you're doing a disservice to at least some of those who have the di02 gene defect by so roundly dismissing the beneficial effects that t3 and/or ndt may have upon them.

    BTW; the ndt also helped with some of my other remaining symptoms as well as the issues with cognition

  • I find L-T3 has a dramatic effect. I've no idea whether I have the polymorphism. The point is that the research shows that the effects of the polymorphism is small press.endocrine.org/doi/abs... . The amount of T3 produced by the thyroid is small (about 6 mcg). However, many of us require a lot more than 6 mcg of L-T3 (plus L-T4) or NDT.

    So it looks like our need for T3 containing medicines is not due to the polymorphism but due to some other problem (which is the case for those patients on L-T3 without the polymorphism).

  • Yep read the paper. I realise that you're making a point that t3 should be available whether or not you have the polymorphism but the research says quite clearly that the cognitive effects for people with the polymorphism are proven. For both hetero and homozygous.

    I can say it makes a massive difference to my cognition and while I do understand that you're making a point I think you shouldn't belittle the effects by presenting it in such a trivial light. I had enough of doctors treating me poorly and telling me there was nothing wrong with me, on this forum I think we should respect that everyone is different.

    You could get tested for the polymorphism which would then enable you to ascertain whether your improvement on T3 might be due to the polymorphism or another factor. I suspect there are a number of factors at play but it should also be noted that t4 works well for the majority of people; the alternatives such as t3 and ndt should be available to those of us for whom it doesn't

    The really scary thing is that I didn't realise that my cognition had been so affected until after I took ndt, I felt so much better on t4 (because I was like a walking corpse beforehand) that the sudden increase in brain power wasn't expected because I didn't know o was still so impaired

    However I'd say it took about a year to fully kick in (for things like personality restoration) and this study was of relatively short duration

  • Yes T3 can make a massive difference. The polymorphism makes a small difference. Those with the polymorphism in both genes will miss up to around 6 mcg of T3. If you fully recover by taking up to 10 mcg of T3 then indeed your condition may be due to the polymorphism. If you require more than 10 mcg then it is definitely not due to the polymorphism.

    Bear in mind that most patients do not have the polymorphism but may still require T3. Most patients who require T3 require more than 10 mcg. Most patients who need T3 do not have the minor cognitive impairment caused by the polymorphism, they have major problems.

    The polymorphism allows doctors to rationalise prescribing T3 but it does not explain the serious symptoms that patients have. Purely from a science point of view the polymorphism is a minor issue. From a practical point of view it enables some patients to get T3 treatment.

  • Yep. I'm gonna wave my bit of paper at my GP. :-)

  • Jim111

    I don't think you're correct but I think that your view is too entrenched so we're never going to agree. As such I don't think it worth further discussion as our interpretations of the relevant paper are too diverse to allow a meeting of the minds on this issue.

  • Just think of all the patients without the polymorphism who have exactly the same symptoms and need T3. I required more than 10 mcg liothyronine (which is more than the 6 mcg produced by a failed thyroid gland) and so the paper cannot explain my condition.

    As long as those who need T3 get T3 the paper is academic, it only matters if you want to discover the underlying aetiology.

  • It's looking like along side 75T4 I need 20T3, maybe 25 to avoid major symptoms through the day and not wake up with nasty symptoms. I suspect adrenal insufficiency plays a part as I can choose hydrocortisone or T3 to kill most of my symptoms during a night time flare up. But GPs and endos are even more scared of low dose steroids than they are of thyroid hormones beyond TSH "normalising" doses of L-T4. I KNOW my story is more complex than hypothyroidism, but if I can achieve a good quality of life with the tools available to me, then why should I not be allowed to make a personal risk assessment of the costs/benefits of using them?

  • Hi Jim111

    If you read my responses carefully you'll see that I'm not saying that people without the polymorphism shouldn't receive t3/ndt and/or a combination that suits them. What I am objecting to is you being so dismissive of the effects of the polymorphism.

    I believe that hypothyroidism is a more complicated illness than the majority of the medical profession believe and that there is insufficient research into the various factors that predicate how well an individual will respond to treatment.

    To date they have identified a single factor that shows a requirement for T3; there may be others as yet unidentified.

    By dismissing the effects of the polymorphism as minor you are doing those with it a disservice. Particularly since you're misquoting the paper and stating that only those with the homozygous variant need to take t3 amongst other things.

    This forum is supposed to be supportive not to be about 'my symptoms are worse than your's' one upmanship.

    One other thing I would note; you've indicated that you react better to t3 and have stated that you haven't actually been tested for the polymorphism. As such how do you know whether your relief of symptoms with t3 is due to the polymorphism or not? One area of research I think would be fruitful would be to test everyone who doesn't do well with t4 only, identify how many have the polymorphism and then to start looking for other common factors in the remainder to see whether other genetic, environmental or other factors could be identified. This would then enable for these to be also tested at diagnosis so that the right treatment pathway could be prescribed.

    One thing I'd also note; when you are blithely stating that on 6 micrograms are required by anyone with the polymorphism and providing this as a treatment plan you are making gross assumptions not merely that the person does not have any other factors that affect use of t3 and that dosages in the relatively small study that we're both quoting are correctly titrated.

    There is further research on the effect of di02 and t3 that I have read but again I'm on a phone so can't post links easily. These are mainly animal experiments but further support the premise that those of us with the di02 gene snp require t3 to function properly.

    So, I'm not saying that you shouldn't campaign for people to receive individualised healthcare as that is a goal that I too strongly support, I'm just asking you not to be so abusive and dismissive of those of us who have the di02 snp. It's misleading to people who may have this and may not have the full information on it plus it's trivialising the suffering of those of us with it that have gone through hell before we received proper treatment.

  • Having read the paper yet again, it is quite fascinating and raises many points. I believe there are a lot of misconceptions about what the research means. The best way forward is for me to put up a separate post specifically about my view of the paper and what it reveals. This will take quite a while as there is a lot in it. When I have completed it I will try and remember to post a brief note in this Post so that anyone interested will get a reminder. I'm wary that I'm in danger of hijacking this post.

  • Hi there

    I found that I managed to get back to being me as opposed to a shadow of me by taking Naturethroid NDT; however everyone is a bit different and what works for one doesn't work for all. I have a single dodgy di02 gene BTW.

    I do takesupplements of b12, b9, b6 and Epsom salt baths (low but in range for the former three) which also help.

    I do see a private endo In London who seems well informed on di02 so pm me if you want his details.

    Good luck

  • I have pmed you. Thank you. Today I took 10mcg T3 at 8am. By 4pm I was yawning tired, feet were hurting and my pulse rate was 88bpm and thudding for no reason whatsoever. I took 5mcg T3 and within an hour everything had settled, 69bpm. Is this anyone else's experience and is this a good way to tell when to re-dose with T3? It does look like I am going to need a lot of T3. I can't get through the night without waking with nasty symptoms which go away within an hour when I take 5mcg.

    Thank you.

  • I started out taking my ndt in a lump first thing in the morning and found I became symptomatic in the evenings. My endo suggested splitting my dose so I take 1 in the morning and one around 3 to 4 pm most days. If I'm having a night out then I may wait and take the second dose later.

    T3 has a shorter life in the body so it may be that you're burning off the morning single dose. Give splitting it a try and see if it helps

    Good luck!

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