IN A NUTSHELL - I have had a suppressed TSH (<0.01) and a slightly elevated T4 for 7 months now and I'm wondering / concerned whether I could be causing any long term damage to thyroid.
BACKGROUND - I got diagnosed with Hashimoto's and Grave's 4 . 5 years ago (Feb 2017) here in the UK with a TSH of <0.02 and free T4 of 22.5. My TSH receptor antibodies were 4.1 and my TPO antibodies were 310. My free T3 was consistently in range at around 5.0. Back in 2017 it only took 3 months for my TSH to show signs of waking up/kicking in and so in the end I never went on carbimazole and my TSH and T4 returned to normal ranges in 6 months where they remained until March 2021.
CURRENT - In March this year my blood results were TSH <0.01.> and have remained there. My free T4 was 34. Since March my Free T4 has been 16 (April), 23 (April), 20 (June), 19.6 (Sept). My Free T3 was out of range for the first time in March this year and was 7.8. It was 6.9 in April. My TSH receptor antibodies were 8.0 in April and my TPO antibodies were 505 in April.
Q1 - My question as above is could I be causing any long term damage to my thyroid with my levels being outside the normal range for a pro-longed period of time (currently 7 months).
Q2 - Does anyone have any advice given my Free T4 is likely only slightly elevated from my normal? (For Info back in 2017 my TSH started waking up when my Free T4 was 19.2) It's currently 19.6.
Q3 - I am not sure if there is any significance to my Free T3 being out of range (high) in March '21 for the first time in 5 years and what this actually means?
Q4 - Free T4 reference ranges seem to vary?! My original Endocrinologist's Ref ranges were 12-20, then 12-22. However I have moved and my new local hospital range is 7.9 -14.4 which if I go by this I've been Hyper and out of range for almost all of the last 5 years!! Can anyone help with this?! Somewhat losing the will.
Many thanks in advance for any help and thoughts.....
Emma :o)
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EmmaC78
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Essential to regularly retest vitamin D, folate, ferritin and B12
What vitamin supplements are you currently taking
Are you already on strictly gluten free diet
If not, get coeliac blood test done BEFORE considering trial on strictly gluten free
Poor gut function with Hashimoto’s or Graves’ disease can lead leaky gut (literally holes in gut wall) this can cause food intolerances. Most common by far is gluten. Dairy is second most common.
According to Izabella Wentz the Thyroid Pharmacist approx 5% with Hashimoto's are coeliac, but over 80% find gluten free diet helps, sometimes significantly. Either due to direct gluten intolerance (no test available) or due to leaky gut and gluten causing molecular mimicry (see Amy Myers link)
Changing to a strictly gluten free diet may help reduce symptoms, help gut heal
Before considering trial on gluten free diet get coeliac blood test done FIRST just to rule it out
If you test positive for coeliac, will need to remain on gluten rich diet until endoscopy (officially 6 weeks wait)
If result is negative can consider trialing strictly gluten free diet for 3-6 months. Likely to see benefits. Can take many months for brain fog to lift.
If no obvious improvement, reintroduce gluten see if symptoms get worse.
The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported
In summary, whereas it is not yet clear whether a gluten free diet can prevent autoimmune diseases, it is worth mentioning that HT patients with or without CD benefit from a diet low in gluten as far as the progression and the potential disease complications are concerned
Despite the fact that 5-10% of patients have Celiac disease, in my experience and in the experience of many other physicians, at least 80% + of patients with Hashimoto's who go gluten-free notice a reduction in their symptoms almost immediately.
Hi SlowDragon, thank you so much for your very helpful and extremely in depth response, it is very much appreciated. Thank you for the information of how essential it is to regularly retest vitamin D, folate, ferritin and B12. I will ask my GP to test for these. My Vitamin D and B12 should be fine (I'm on high strength of both) but my ferritin has historically often been low even when I'm taking supplements which has triggered a number of doctors suspecting Celiac. I have had a number of celiac tests however I am fairly sure I had already considerably cut out gluten before I had any of them so I'm not sure I'll ever know. My niece got diagnosed with celiac at 2.5yrs old and I have had problems with my stomach since I was 13 and on and off omeprozole until 4-5 years ago. I don't think my folate has ever been taken.
Supplement wise I am taking Vit D, Vit C, Vit B, Magnesium, Sea Buckthorn, Omega 3, Krill Oil, Calcium, Zinc, Vit A, Selenium and very recently I have started Iron and Folate.
Interestingly going Gluten Free was one of the first things I did in the summer of 2017 (3 months after diagnosis give or take) and despite being very strict noticed little difference symptom wise (although my T4 and TSH did stabilise). I did "The Happy Gut" protocol in 2017 and have done two or three of the "Auto-immune Reset" diets where one cuts out every inflammatory food and all grains etc and carbs and only have very very minimal fruit. Interestingly in complete desperation around May 2020 I cut out dairy and finally cut out sugar (my weakness) a month or two after and the brain fog just lifted and I suddenly felt like I had a little bit of energy. I got stressed and it all went down hill over the winter of 2020 despite being very strictly off gluten, dairy and minimal coconut sugar. My stomach is so much better now although a stool sample identified that I am unable to break down fats so I was taking Beta TCP but haven't for a few months. My oxygen levels have often been around 97-98% and my blood pressure is quite low although slightly more average being hyper-thyroid. I maybe now have the occasional sour dough brunch or chips where I was out and don't want to cause a fuss. In the past my glucose levels have shot up to 13.1 and also crashed at 2.4 so I definitely think sugar does not agree with my system. When I have a little sugar now, for some reason I always wake up absolutely starving?!
My diet has been pretty impeccable since March when I did another "auto-immune reset" diet but annoying my bloods on 20th March were out. This may have been because I accidentally started some fulvic minerals and didn't notice traces of iodine in the ingredients.
(your response was so very helpful, I will read all of those articles at the weekend)
Thank you again, Emma xx
Do let me know if anything else springs to mind with my response above?
Supplement wise I am taking Vit D, Vit C, Vit B, Magnesium, Sea Buckthorn, Omega 3, Krill Oil, Calcium, Zinc, Vit A, Selenium and very recently I have started Iron and Folate
Important to test folate, B12 at least annually
Vitamin D testing twice a year
Never supplement iron unless full iron panel test for anaemia shows low iron
Low ferritin doesn’t necessarily mean low iron too
Can you say a little more about why one shouldn't supplement Iron unless full panel test for anaemia shows low iron? I think my Endo once said I wasn't anaemic but low iron levels has been a regular theme when I was much younger.. Are these panel tests easy to try and ask GP for and how could I persuade them to do a full iron panel test? (not usually easy to get bloods without an good case).
Would you mind saying more about the "low ferritin doesn't necessarily mean low iron"? The lowest my Ferritin has been is 19 (20-200) the highest it's ever been is only 63.
Eating iron rich foods like liver or liver pate once a week plus other red meat, pumpkin seeds and dark chocolate, plus daily orange juice or other vitamin C rich drink can help improve iron absorption
This is interesting because I have noticed that many patients with Hashimoto’s disease and hypothyroidism, start to feel worse when their ferritin drops below 80 and usually there is hair loss when it drops below 50.
Thyroid disease is as much about optimising vitamins as thyroid hormones
Hi SlowDragon, oh my goodness thank you SO much this is so very helpful and appreciated. I have booked in a blood test for full panel iron, ferritin, b12, vit D and folate for later this month!
Do you have/know any recommended or optimal levels of these for people with Auto-immunes? (Table of bloods attached below if easier to view)
Vitamin D - orginally it was <50 but it's been as high as 149 and last time is was 127
Ferritin - 19 was the lowest and 63 has been the highest (range 20-200)
Serum Iron - 8.7 has been the lowest, last test it was 14.8 (range 6.6 - 26)
UIBC - 29. 6 originally highest 43 (range 20-62)
Iron Binding Satn - 16 has been the lowest, 30 the highest (range 15-50%)
B12 - 380 has been the lowest, 670 the highest (range 197-771)
Q1 - My question as above is could I be causing any long term damage to my thyroid with my levels being outside the normal range for a pro-longed period of time (currently 7 months).
Not as far as I know, no. T4 is basically a storage hormone which doesn't so anything much until it's converted to T3. Your FT3 would not appear to be very much out of range, but you haven't given the range, so hard to say.
Q2 - Does anyone have any advice given my Free T4 is likely only slightly elevated from my normal? (For Info back in 2017 my TSH started waking up when my Free T4 was 19.2) It's currently 19.6.
What do you mean by 'waking up'?
Q3 - I am not sure if there is any significance to my Free T3 being out of range (high) in March '21 for the first time in 5 years and what this actually means?
Difficult to say without more detail. Always best to give all the numbers: dates, results, ranges for all three hormones: TSH, FT4, FT3. That way we can see if there's a pattern of some sort.
Q4 - Free T4 reference ranges seem to vary?! My original Endocrinologist's Ref ranges were 12-20, then 12-22. However I have moved and my new local hospital range is 7.9 -14.4 which if I go by this I've been Hyper and out of range for almost all of the last 5 years!!
No, that's not the way it works. Ranges do vary from lab to lab, depending on the machine they use and the local population. And, you have to use the range that came with your results, not just any old range.
Hi Greygoose, thank you so much for your response, I will try and post my Table of Blood Results but not sure you'll be able to read them?
Q1 - My FT3 range was 3.1-6.8pmol/L. The highest it was in March '21 was 7.8, the last time I had it done is was 6.9. Does that help?
Q2 - by 'wake up' I probably mean kick in/start working again ie that my T4 went low enough for my TSH to be needed and start working/firing again. That was how the endocrinologist explained it. They said when my T4 is high the TSH is kinda redundant so lowers. Is this your understanding of how it works.
Q3 - See pic that I'll try and attach. Fingers crossed you can make it larger. NB. On the readings where TSH is <0.005 - see the lower GWH range.
Q4 - I did try to check the range of my local NHS Endocrinologist (GWH) where it said it was 7-14 and they did say it was pmol/L? Currently on the usual range it is 19.6 (private hospital)
Q1 Your FT3 is not a lot out of range. And, given that you have Hashi's, that's not surprising. Do you know how Hashi's works?
Q2 What a very understanding endo you have! Most of them have no idea why TSH behaves the way it does! lol But, it's not just a question of the FT4, the pituitary reacts to both FT4 and FT3, and if both are over-range, the TSH is going to be suppressed because the pituitary knows that the thyroid doesn't need stimulating anymore. There is enough thyroid hormone in the blood so the TSH is redundant. When these levels go down, the pituitary produces more TSH to stimulate the thyroid to make more hormone. That's the way it works.
Q3 Yes, I could read your chart. And the significance of the high FT3 was more than likely that you were having a Hashi's 'hyper' swing. That's what Hashi's does. It swings between hypo and false 'hyper'.
Q4 OK, but you still have to use the ranges that go with your results. You cannot pick and chose which ranges you're going to use. Doesn't matter what ranges other labs use, you need to go by the ranges used in the lab that did your analyses.
Q1 - I understand that Hashi's can swing over or under but I am never had results of it being Hypo (I don't think). In answer to your questions, I'm not sure I really understand how Hashi's works?
Q3 - Hashi's swings between Hypo and false 'Hyper'... you've got me intrigued? Also how low to results have to go to indicate Hypo? I think my lowest T4 was 12 so not sure I've been Hypo over the last 5 years.
Q4 - I understand that I can't pick and choose the ranges it's just been very challenging to get the ranges from the NHS. I got them over the phone and they seemed to indicate the same pmol/L but yes I will keep the results of the private vs NHS separately.
Q1 No, Hashi's doesn't 'swing under', it is basically under, and sometimes swings over - if that makes sense. But, you also have Grave's antibodies, so that makes things a bit more complicated, and I'm not sure how that works when you have the two together.
But, a brief rundown of Hashi's:
OK, so Hashi's is an autoimmune disease, where the immune system attacks and slowly destroys the thyroid. It is diagnosed by testing Thyroid Peroxidase (TPO) antibodies and Thyroglobulin (Tg) antibodies.
Contrary to popular belief, it is not the TPO/Tg antibodies themselves that attack the thyroid:
"When lymphocytes infiltrate the thyroid gland, mistakenly taking it for a foreign bacteria invader, they damage the thyroid gland and release thyroid peroxidase &/or thyroglobulin into the blood stream. These don't belong outside of the thyroid gland so antibodies are developed to mop them up.
The antibodies are a result of the attack on the thyroid gland, the antibodies don't cause the attack."
After every immune system attack on the thyroid, the dying cells release their stock of thyroid hormone into the blood stream, causing the levels of the Frees to shoot up - FT4 to around 30 something, FT3 around 11/12 - and the TSH therefore drops to suppressed.
There is no knowing how long these high levels will persist, but eventually, they will drop by themselves as the excess hormone is used up or excreted, and not only will you become hypo again, but slightly more hypo than before, because there is now less thyroid to make hormone.
(NB: A Hashi's 'hyper' swing is not true hyperthyroidism in that your thyroid is over-producing thyroid hormone. It's physically impossible to 'go hyper' if you are basically hypo. The thyroid cannot regenerate itself to the point of over production of hormones - or even normal production. Very few doctors appear to know that.)
Therefore, it's very important that your doctor does not reduce your prescription, because you’re going to need it again! If you start to feel over-medicated at that point - some do, some don't - the best thing is to stop levo for a few days, then, when you feel hypo again, start taking it again. It's very important to know one's body, and how it reacts.
There is no cure for Hashi's - which is probably one of the reasons that doctors ignore it - apart from the fact that they know nothing about it, of course!
However, between the 'hyper' swing, and the descent back into hypothyroidism, there can be a phase - quite a long one, sometimes - of normality, where the person is neither hypo nor 'hyper'. This is where people sometimes start talking of having 'cured' their Hashi's, by whatever means. But, it doesn't last. Eventually, you will go hypo again.
But, there are things the patient can try for him/herself to help them feel a bit better:
a) adopt a 100% gluten-free diet. Hashi's people are often sensitive to gluten, even if they don't have Coeliac disease, so stopping it can make them feel much better. Worth a try. Some say that going gluten-free will reduce antibodies – I’ve never seen conclusive proof of that, but, you should be aware that even if you were to get rid of the antibodies completely, you would still have Hashi's, because the antibodies are not the disease. It is not the TPO/Tg antibodies that do the attacking.
b) take selenium. This is not only reputed to reduce antibodies, but can also help with conversion of T4 to T3 - something that Hashi's people often find difficult.
Q3 How low does the FT4 have to go to constitute a hypo result? Well, you can't just take one reading on its own to diagnose. You have to look at TSH, FT4 and FT3. But, an FT4 of 12 when 12 is the bottom of the range would be hypo in my book. A euthyroid FT4 would be around mid-range.
Q4 It's not about the units - pmol/L - it's about the bottom number and the top number. They are what vary from lab to lab.
A really interesting read greygoose thank you so much. I think having both H & G does complicate things I'm told. I have never been told I'm hypo (I'm stick think as well) but with the ranges being 12-20, I feel it's hard to tell when TSH in normal range. My Endo did say that when my TSH goes above 2.0, there is more of a risk of going hypo and checking my blood results, they were over 2.0 in October. Ironically that month was the first month that my TSH Receptor anti-bodies were in the "normal range" and I was so excited as I thought I had reversed it so v interesting what you say about this. Interestingly despite being hyper and supressed TSH for 7 months I have more energy than I've had in the last decade, although I'm not sure at what cost ?! I have two questions if that would be ok?
Qu1 - Do you have any guidance on best ways / symptoms of knowing I might be being hypo?
Qu2 - Given everything you know would you have any recommendations re: carbimazole and radioative iodine etc (I know you're not a doctor) just interested really as don't have any friends with this knowledge to help x
Qu1 - Given that so many symptoms can indicate both hypo and hyper states, the only sure way to know which you have is to get your FT3 tested. Just testing the TSH is totally inadequate because when one has/had Grave's, the TSH is wholly unreliable. It will not tell you what your FT4 and FT3 are. And the unique presence of a suppressed TSH is not an indication of thyroid status. If your doctors are relying on the TSH to treat you, then they know absolutely nothing about thyroid.
Qu2 - I know nothing about carbimazole, I'm afraid. I don't have Graves. I only know what I've read on here - i.e. that if it suits you, there's no reason why you shouldn't take it indefinitely. Doctors only want you to have RAI/surgery for their convenience, not yours. And, many people regrete the lose of their thyroid. RAI is not without risks for the future. It's not as anodine as they would have you believe. And, total thyroidectomy carries all the usual risks for surgery. So, if you're happy on carbi, then I would say 'stay on it'! But, as I say, I have no personal experience, just what I've read.
Q1 - My question as above is could I be causing any long term damage to my thyroid with my levels being outside the normal range for a pro-longed period of time (currently 7 months).
Your immune system Is attacking your thyroid causing the stimulation (Graves & over activity) and damage from Hashimoto’s (ultimately leading to hypothyroidism)
What your levels are as a result of disease or if medication were given it doesn’t cause any additional damage.
When levels are high causing the TSH low this does “damage” the feedback loop, which mean the TSH can stay sluggish and low. The technical term being hypothalamus–pituitary–thyroid (HPT) axis down regulation.
Your FT4 & FT3 need to be tested not TSH alone.
Q2 - Does anyone have any advice given my Free T4 is likely only slightly elevated from my normal? (For Info back in 2017 my TSH started waking up when my Free T4 was 19.2) It's currently 19.6.
Your aim should be to keep FT4 & FT3 are in range. Your TSH may have started rising if FT4 or FT3 was low.
Q3 - I am not sure if there is any significance to my Free T3 being out of range (high) in March '21 for the first time in 5 years and what this actually means?
Often high FT3 is due to erratic release of hormone in the thyroid rather than conversion from FT4. Usually medication is adjusted to lower both levels. Balancing the FT4 & FT3 can be particularly difficult with Hashi & Graves.
Q4 - Free T4 reference ranges seem to vary?! My original Endocrinologist's Ref ranges were 12-20, then 12-22. However I have moved and my new local hospital range is 7.9 -14.4 which if I go by this I've been Hyper and out of range for almost all of the last 5 years!! Can anyone help with this?! Somewhat losing the will.
Ranges do vary between lab machines. Each result has to be interpreted using the given range. It not a case of applying a chosen range to any given results. The result would be different for each test but the % through the range should be similar.
To contrast between different ranges you can calculate the % of each range and compare between the result
I agree with all these answers. If possible your doctor should try and get your hormone levels down a bit without making you hypo. This is because if TSH is suppressed for a long time the axis can be down-regulated leaving you with a long term low TSH. The problem with this is your T4 to T3 conversion rate will be reduced leading to problems. Doctors tend not to remember (or know of) the role TSH plays in deiodinase.
I think the OP didn’t start carbimazole because FT4 & FT3 didn’t remain over range & TSH did start responding.
They were asking about thyroid damage & I went slightly off track with axis down regulation.
Although its very difficult to judge if very low TSH should be treated if levels not continuously over range.
I agree the longer the TSH low the worse is it for “the axis”
I know my TSH was suppressed (as in <0.01) 4 years before diagnosis. Which I discovered by going through historical hospital records. The doctors didn’t advise me. Fortunately my FT3 levels were not excessively high as I have a nodule not Graves.
When I was diagnosed my FT3 was almost double, I hadn’t noticed symptoms as they had developed so slowly.
I have now been euthyroid for 3 years apart from 1 occasion a year into treatment, when after tinkering with carbimazole & propranolol caused FT3 to go to 104% of range.
Last year my FT4 was kept at about 40 - 30% of range and the FT3 was 20 - 10% of range, even going 20% under range at 1 point. The highest my TSH went was 0.31 (0.35 - 3.50) I was so hopeful it would go into range but the following test it dropped.
I felt worse with low levels than in the year I was diagnosed hyper (& diabetic)
Even though since then I had lost 90lb and gone from 3000 to 15000 steps a day and lowered my diabetic levels to normal through diet & exercise.
I wonder if I should persevere with the low levels in hope the TSH will eventually respond or accept its forever broken and allow my levels to rise to mid range.
I'm in a similar situation as I needed high dose hormone treatment for a decade. I've tried a couple of times to get my axis back by going hypo for several weeks and feeling dreadful to no avail. For some people the axis recovers for others it doesn't. I'm guessing this is related to how suppressed TSH was and for how long. There is weak evidence that a TRH stimulation test might kick the axis back into normal function. An endocrinologist promised me he would do one but later simply said no, I think he was lying and just trying to get me off liothyronine. I simply take the lowest dose of hormone (50 mcg L-T4 + 30 mcg L-T3) that I feel well on and hope.
I feel this is a very important issue that is overlooked, which is why I keep reminding people of it.
It states, "In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio."
Does this suggest older people who try raising their TSH in the hope of restoring their axis and increasing peripheral deiodination will be unlikely to see this happen?
I've seen this study quite some time ago. We shouldn't read too much into it as it looks at TSH, fT3, fT4 levels across populations rather than sequentially in individuals. For example, if someone's fT4 falls TSH rises and this causes more secretion of T3, T4 and more T4 to T3 conversion. This could be demonstrated if they analysed a series of blood tests from an individual. We see this deiodinase effect most strikingly in Graves' disease where TSH receptor antibodies cause very high peripheral deiodinase.
I also think the study is subject to a little bias because the data comes from blood requests from GPs, although they took care to exclude people with recognised thyroid disorders the cohort will have included those of us who are hypo and told we are normal because the blood test says so.
Nonetheless I think the results are useful. It is likely TSH is higher in the elderly because it is less potent, TSH consists of multiple isoforms with varying bioactivity. Elderly people may produce less bioactive TSH and so need more of it, this reduced bioactivity could led to reduced stimulation of deiodinase.
The conclusion 'This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age' is inaccurate. If you look at the numbers the fT3 / fT4 ratios are very similar in all age groups except the over 80s. It is the relationship between TSH and deiodinase that is decreased not the level of deiodinase activity.
Thanks for your reply. There are so often shortcomings with these studies and a paucity of well-designed large-scale RCTs . For this study, I'm amazed they found over 500,000 samples that included TSH, FT4, and FT3. The latter is so often left out. (maybe it's more commonplace in Jerusalem.) They also excluded samples with a TSH below 0.2. If you're wondering whether it's possible to recover a very low/suppressed TSH in order to have increased T4 to T3 conversion, I suppose it's possible the results may not even apply in that scenario. And can we be sure the deiodinase effect seen in Graves Disease would apply outside those particular circumstances. I don't expect an answer, just points to the difficulties in extrapolating data from one set of circumstances to another, particularly when the studies themselves leave something to be desired.
From your reading, appr. how high would the TSH have to get to see the benefit in deiodinase? Are we talking about the dreaded 'normal' range? Apologies if you've mentioned already.
That's an impossible question because nobody has done the research to accurately find a good relationship. An added complication is that TSH is composed of a number of isoforms with varying bioactivity. So, a TSH of 1.0 for one person may be up to four times as bioactive as another person with the same TSH 1.0. I can give my own example.
In 2000 I had TSH 1.0, fT3 4.9, fT4 13.3
11/01/21 TSH 2.73, fT3 2.7, fT4 9.7
I was not taking thyroid hormone at the time of both blood tests. During the the first 10 years of the 2000s I needed high dose thyroid hormone with down-regulated my axis. As far as I know my thyroid gland is healthy, never had any auto-immunity.
So, you can see that even though my TSH was higher it stimulated less thyroidal secretion and a much lower RATE of deiodinase. This suggests that the TSH in 2021 had much lower bioactivity. Unfortunately it is not possible to get a TSH bioactivity blood test. Bioactivity is measured by obtaining thyroid cells (e.g. some healthy cells from a thyroidectomy or from a mouse) and measuring the TSH effect on the cells in vitro.
I think to have an effect TSH would need to be within its reference interval but that's a pure guess. The way to see is to look at fT3 and fT4 when fT4 is around average fT3 should be near average. fT3 / fT4 ratios are useless, the ratio changes with fT4.
Hi jimh111 and wellness1 .. i once went searching for this .. ie how high does TSH have to be to get benefit to conversion from deiodinase activity ? .. and does it keep getting better with higher TSH ? I found one snippet in a study which was a bit over my head , but i made myself the following note:
"high tsh only increases Dio actiity in thyroid gland + other TSH receptor tissues (peaks at 1/ decreases at >1)"
Which surprised me .... i thought it would continue to increase with more TSH.
The bad news is that because i'm a numpty, i didn't record the name of the study on my note , and the only way to find it again is to re read all of the 100 or so studies i've got bookmarked ..... but if i do ever find it again i'll let you know where i read it .
I think high levels of TSH stimulates deiodinase. This is because TSH receptor stimulating antibodies in Graves’ disease can produce high levels of peripheral deiodinase causing high T3 levels.
Yes i thought that would be the case ... wish i could give you the quote i refer to .. i suspect you'd have understood it's meaning /context better than i could.... have just been having a look and so far have looked at about 12 study's on my list that are 'not the right one' ... i'll get back to you in about January with the results of further rootling about in my bookmarks list .....
I haven't chased up where she got if from .. because it's all at the edge of my comprehension anyway. but since it's from Tania i assume there is a reference to a paper .
"D1 and D2 are also both upregulated by higher TSH, but only in the thyroid gland and other TSH-receptor expressing tissues, and under certain conditions:
TSH signaling can be blocked by the TSH-receptor-blocking antibody (TBAb). This antibody is found in approximately 11% of patients with hypothyroidism using special assays for blocking antibody detection (Diana et al, 2018).
According to new research, TSH’s upregulation of DIO2 in the human thyroid gland peaks at around 1 mU/mL and begins to diminish as TSH levels rise above 1 mU/mL. In contrast, TSH receptor stimulating antibodies (TSAb, which cause Graves’ hyperthyroidism) do not decrease DIO2 expression but continue to enhance it (Jang et al, 2020).
D2 is not upregulated directly by TSH, but by cAMP signaling in cells.
cAMP is short for “Cyclic adenosine monophosphate.” It is a “second messenger” signal that is produced in the cell after certain types of receptors, such as TSH receptors, are activated on the cell membrane.
The primary mechanism by which TSH upregulates D2 is through generating cAMP signals inside the cell.
The DIO2 gene has cAMP-responsive elements that make it capable of sensing cAMP (Wang et al, 2010).
But TSH is not the only hormone that can send this signal to upregulate DIO2. Many other substances and hormones besides TSH can generate cAMP signals.
This is good news for treated thyroid patients who have a suppressed TSH, or a TSH deficiency due to pituitary dysfunction."
No need for reply ... just adding it here while i found it .. get back to your decorating
Haven’t seen this document so very quickly skimmed it. It’s a bit skittish and not as clearly written as Tania’s other articles, so more difficult to follow.
Many tissues express TSH receptors and deiodinase, so can have conversion up regulated by TSH.
The bit about D2 activity in the thyroid at TSH 1 is interesting, I will follow it up in a few months time. Other tissues likely differ. The thyroid expresses mainly D1 so D2 has a minor role. It’s remotely possible the TSH isoforms differ as TSH goes above 1 and the pituitary is less sensitive to these forms - this could explain the different behaviour of TSH and TRAb. Just speculating, could even be an error in the research.
Yes, TSH stimulates D2 via cAmp. I tried taking forskolin (cAmp agonist) to improve my conversion, it seemed to work but also lowered my TSH - net benefit zero. This might work when TSH is close to zero, when there can be no effect on TSH. (If you increase cAmp it will increase D2 in the pituitary causing fT4 to have more suppressive effect on TSH). So, maybe a cAmp agonist such as forskolin could help patients on levothyroxine who have a degree of central hypothyroidism or reduced D2.
yes, i remembered when re reading quote that she was only discussing deiodinase in thyroid tissue, so the combined effects of deiodinase in other tissues probably alters the relevance to the overall situation. .. i'd book marked it try and understand more later, and then never got round to it .... too busy pulling nails out of floorboards ...wish i was at the stage of 'decorating', ... but am still at the 'pull the building to pieces' stage....
In the two articles below , she refers to getting some information from The Human Protein Atlas , detailing which tissues have each deiodinase.. but does mention there may be 'issues' with the tissue samples used for analysis ...
Lol .... 'Skittish ' ... good description.. yes, she is a bit isn't she ... sometimes i struggle to follow her thought process .... but her brain is probably rather full , so i'll let her off...
Thanks for the links. Although it is my area of interest I will have to overlook these for now as I'm busy with work at home and my T4 cancer project. I need to prioritise or I get nothing done. I only meant the one article was a bit skittiish, in general I find her stuff very readable given the depth and complexity.
Well done finding it and thanks for posting it here. Not surprised Tania Smith is the source. Just had a quick skim and it looks intriguing. Will look forward to any future discussion that provides more insight into this and its practical application for those on replacement therapy. I'll look for that once you and jimh111 have made progress on your home improvement (and other) projects.
Hi Jimh111, thank you for your response.When you say my doctor should try and get my hormone levels down are you referring to T3 and T4 (I'd never thought of these as hormones)... If relevant I've gone in to early menopause and have started HRT just over a month ago so not sure how this is going to affect all of this! I hadn't heard of deiodinase until you mentioned it, I had to look it up! Thanks for highlighting the down-regulating and conversion issues with a long term TSH suppression. Would carbimazole potentially address these issues?
Yes, I meant fT3 and fT4. Just get them down with carbimazole, just enough so you feel good and TSH can be a little higher. T3 and T4 are thyroid hormones whereas TSH is a pituitary hormone. I don’t know anything about female hormones other than the menstrual cycle affects TSH but not fT3 and fT4.
Thanks Jimh111 that's really interesting re: Thyroid hormones, pituitary hormones and menstrual cycle only affecting TSH (not FT3 and FT4). I've had blood test results back from 4 Nov and my FT3 and FT4 are now in normal (mid) range but my TSH is still <0.01. Hopefully TSH will now start to increase 🤞
Many of us have a suppressed TSH and have had for years. If that negatively affects conversion, we just have to take more T3. I don´t think anyone should remain symptomatic simply to achieve a given number on a lab sheet.
Q1 - I am not sure I completely understand your response. My Immune system is attacking my thyroid does sound like permanent damage could be being done. Does Hashi always lead to Hypo, I am not sure I've experienced Hypo in the last 5 years only two episodes of Hyper. It seems you say the biggest issue is the damage to the 'Feedback loop' with having a low TSH. I'm not sure I've heard of the HPT.... would it even stay sluggish if my T4 came down do you think? So would something like carbimazole potentially help this in your opinion? Yes I've always had my TSH, Free T3 and Free T4 done. March '21 was the first time my F T3 had ever been elevated, interesting what you say about this often being due to erratic release of hormone in the thyroid.
Q4 - Thanks for the calculator, it seemed to be in a foreign language so I struggled to make sense of it (probably me).
Q1 - I am not sure I completely understand your response. My Immune system is attacking my thyroid does sound like permanent damage could be being done.
You have both Graves & Hashis?
Thyroid Peroxidase (TPO) which are often present in both conditions.
TSH receptor antibodies (TRab) which is accepted as evidence of Graves. Although you have not have levels typical of Graves - which often has readings of undetectable TSH and FT4 \ FT3 level over 3 times the normal range.
With Graves thyroid-stimulating immunoglobulin (TSI) are produced by the immune system with cause the thyroid to enlarge and over produce. The TRab test measures TSI (which stimulate and activate the thyroid) as well as “blocking” Thyrotropin binding inhibiting immunoglobulins (TBII) & the “neural” (which don’t have a name as newly discovered). Not everyone with positive TRab goes hyper. Many hospital favour TSI as more accurate with Hyper & Graves. It’s possible for the stimulating to stop & the function returns to normal.
Antibodies are helpful for diagnosis, as positive results confirm autoimmune but it’s unknown how to treat and affect them, they fluctuate and there is often a cross over in conditions.
With Hashis Initially the damage cause swelling and as the thyroid cells are destroyed, hormones are released which causes a temporary rise in levels.
Then over time there is a reduction in the healthy thyroid which leaves in unable to produce enough thyroid hormone & yes this is permanent.
It’s the immune system doing the damage not where your FT4, FT3, or TSH happens to be.
The antibody are clearing up the foreign chemicals in your system from the attacks, so these aren’t responsible for the attack either.
Does Hashi always lead to Hypo? In the overwhelming majority of cases - yes.
In theory, a very mild case which could result in slight damage which the thyroid can later compensate for, but the norm is continued destruction & permanent hypothyroidism.
I am not sure I've experienced Hypo in the last 5 years only two episodes of Hyper.
Continued monitoring required as your levels could either rise again or decrease. It’s the levels which are treated not the immune system.
It seems you say the biggest issue is the damage to the 'Feedback loop' with having a low TSH. I'm not sure I've heard of the HPT.... would it even stay sluggish if my T4 came down do you think?
Impossible to predict. It might respond quickly to low(er) levels or you might need under range levels for weeks (making you unwell). & even then theres no guarantee it will rise. You could try to lower levels slightly to see if it responds. But if your not currently requiring antithyroid to lower over range levels starting it to test TSH may not be appropriate.
I believe it’s the length of time it’s affected. I had very gradually rising levels and a very fractional elevation in FT3. Totally suppressed TSH, 4 years later my FT3 was nearing double, started carbimazole treatment but TSH has never risen into range, that’s nearly 3 years later.
So would something like carbimazole potentially help this in your opinion? No because, Carbimazole is a medication with risks and should only be given if levels are continuously above range. I don’t think it should be taken to lower in range levels to low levels to correct a low TSH. Doctors who look at TSH will do this as they believe TSH should be in range but it could be to the detriment of the FT4 & FT3.
Yes I've always had my TSH, Free T3 and Free T4 done. March '21 was the first time my F T3 had ever been elevated, interesting what you say about this often being due to erratic release of hormone in the thyroid.
Q4 - Thanks for the calculator, it seemed to be in a foreign language so I struggled to make sense of it (probably me).
I Should have explained is not in English but you just type in result and range it will calculate, number same in any language.
It’s a great deal to learn and understand, take your time you will take in.
Hi PurpleNails, thank you for your response, I have just had another chance to read your response and try to digest i.t
Q1 - Helpful to know that in your view the main damage is to the feedback loop as such.
Q3 - My FT3 and FT4 and TSH have always all been done together. In your opinion, could the reason my FT3 was elevated this second "hyper episode" potentially be because the thyroid is somewhat deteriorating?
Q4 - Thank you for the calculator, I didn't even know these existed. I think I've just figured out how to use it. Is there optimal %'s for each?
Q1 - Helpful to know that in your view the main damage is to the feedback loop as such.
The main damage is from autoimmune issue, the subsequent alteration levels is what can impact on TSH. It’s unavoidable on both counts. Future treatment should focus on ensuring FT4 & FT3 are in range.
Q3 - My FT3 and FT4 and TSH have always all been done together. In your opinion, could the reason my FT3 was elevated this second "hyper episode" potentially be because the thyroid is somewhat deteriorating?
I’m sure others could explain this better, I’ll try, when thyroid starts to fail & FT4 reduces. there are instances where FT3 can rise as it ‘picks up the slack’. The body’s way of prioritising. On the other hard when FT4 rises FT3 can rise disproportionately higher. This occurs with Graves and often Nodules causes higher FT3. The thyroid behaves inexplicably sometimes!
Q4 - Thank you for the calculator, I didn't even know these existed. I think I've just figured out how to use it. Is there optimal %'s for each?
You need to work out what’s optimal for you!
Most healthy individuals have results within these ranges.
Most of us don’t have complete & carefully recorded results from when our levels are “healthy” so we can’t compare to our normal, Would be useful if we did!
When some is taking replacement hormone it’s well documented most feel well when TSH is around 1 (under 2) and FT4 at 75% of range & FT3 50% plus.
It’s usual for FT3 to be lower in range than FT4 but but too great a difference indicates a conversion issue. When FT4 doesn’t convert to FT3 poor nutrient levels can sometimes play a part.
As someone on a antithyroid treatment, my specialist said the aim is the have FT4 mid range & FT3 “any where in range”. So they are pleased my FT4 is 55% & FT3 27% but I think I would prefer my FT3 could be higher.
My understanding is that TSH should be 0.2 or above to prevent any secondary problems with the heart and bones etc. T4 and T3 should be 75% up through the range.
This study academic.oup.com/jcem/artic... found that there was no increase in cardiovascular disease, dysrhythmias, and fractures provided TSH was > 0.04 and < 4.0. The study investigated these limit points, it could have e.g. used 0.05 and 5.0 and perhaps drawn the same conclusion. So, we should see these levels as approximate and part of a continuum.
For an average person fT3 and fT4 will move around their mid-intervals. If both were 75% up they would be thyrotoxic, showing signs and long term effects of hyperthyroidism. Some patients need high hormone levels to be well but this should not be seen as a target. Patients on levothyroxine monotherapy need high normal fT4 to achieve an average fT3 and feel well. This strategy carries a cancer risk which I will post on in a few month's time when I have collated my research.
As mentioned in my earlier posts it is preferable to keep TSH at more normal levels for good T4 to T3 conversion (if you can). A TSH of 0.2 shouldn't present any problems as far as I know (and I'm not a doctor).
Since you are not a doctor, I don´t think you should make statements like that. It would be interesting if, for once, you could actually back up your claims. If it is general knowledge in the medical community that FTs at ca 75% through range leads to thyrotoxicity, why are not all doctors aware of it? Why does Dr. Toft, a specialist, say that high in range or even slightly above range FT4 - with FT3 in range - is safe? How could Dr. Lowe successfully treat thousands of fibromyalgia patients using high doses of T3 only? Do you know something they don´t ? And, why do you keep insisting we should mimic what happens in a person with a healthy thyroid gland? Ours are not healthy. A healthy person does not absorb thyroid hormone from the GI tract. A healthy person´s thyroid gland won´t dump all the hormones in their bloodstream in one go. A healthy person´s thyroid gland will convert some of the T4 to T3. That does not happen in a person with a damaged or removed thyroid gland, so I am personally not at all convinced that we should try at all cost to mimic what happens in euthyroid people. If you feel well on midrange FTs and a normal TSH, good for you, but I don´t think you should be telling others that they need to adhere to the same protocol - unless you have convincing scientific evidence to back up your claims.
I'm not clear which of jimh111 statement's you wanted evidence for , and am not intending to butt in.. but just wanted to say ....
I too started finding small /new suggestions that T4 hormone level (in anyone , not just those on thyroid hormone replacement) had an association with 'cancer proliferation' in cells , a couple of years ago when looking for reassurance about the risks (or not) of my own very high fT4 levels .
This seems to be new stuff , and many of the slightly older references like Toft will not have had the information to influence their statements at the time.
An internet search using "T4 cancer proliferation" will show that stuff is coming out suggesting this could be an issue ( for all T4 ,whether endogenous or exogenous, ... i think )
Since becoming aware of this as a potential issue , i am now less comfortable than i used to be in thinking that it is OK to use high fT4 to get enough T3 from Levo alone.
Tania Smith has started to do some articles looking at new information on this subject.
Like jimh11 .. i have put this new 'T4/cancer proliferation' issue in the 'i'll look into this properly later' box ,... and haven't got round to any further attempts to find out / understand the facts yet.
I wonder if the "higher T4 level / ? cancer cell proliferation" question, may well end up being potentially helpful evidence that those of us using high T4 to feel well, might be safer to use small amount of added T3 to try and regain well being .. rather than using high T4 from Levo to get higher T3.
Obviously, it's all still a matter of relative risk / benefit / individual ability to get well ... and nothing at all to do with 'aiming for a number' whether it be TSH or T4 /3 level.
I'm collating my evidence on this and really want to present it in a balanced way but as a short term issue I personally would not be comfortable with an fT4 in the upper quartile or higher. I would strongly push for some liothyronine so that fT4 does not need to be above average.
yes .. mine recently wandered up from 14 [7.9 -14] to 20, to 22.7 , then back down to 19 , then 16 over a couple of years... and it's been mostly between 75 and 130 % of the range for the previous 15yrs .. so it is a bit of a concern.
however, my previously (0.05ish ) TSH has curiously decided to come up to nearly 2 and seems to be staying there .... so am 'observing ' for awhile to see what happens next, before playing around with anything.
Mmmm ..... since most Doctors haven't yet caught up with the proven information that TSH has a circadian rhythm ... i wouldn't hold your breath on 'hearing it from a Doctor'.
What I would prefer to hear from doctors is that FT4 causes cancer as of a certain level. If that is indeed true, many patients with overactive thyroids are bound to end up with cancer. If that happens I do not know.
I haven't seen enough about it yet to know if 'cancer proliferation' even means the same thing as 'causes cancer' ..If we have a curiousity about the latest 'interesting' findings , we have to accept that it will be many many years before there is enough evidence (one way or another) to get through guidelines makers before doctors will have anything to say to patients on the subject .
No one is saying 'T4 causes cancer ' .. that would be highly irresponsible without MUCH more information ... we are discussing early suggestions of an association.. nothing more .
At the moment i consider it more of a subject of interest to keep any eye on... that's all.... but it's enough to make me pause for thought before continuing to say on here
" a study/quote from a few yrs ago say's there's absolutely no problem with deliberately creating over range/high ft4 with Levo" to do that would be equally irresponsible now i've seen enough to suggest there may be a problem.
I will present the evidence as soon as I have written it up, this will take a few weeks at least as there is considerable research and it's a challenge to sort the wheat from the chaff. I'll try and remember to tag you when I post. The research is by doctors and I'm giving more credence to oncologists than endocrinologists!
I'm drifting away from the topic (deiodinase) but I wanted to point out that levothyroxine monotherapy is not as safe as previously assumed.
I gave evidence that a TSH between 0.04 and 4.0 carried no extra risk. 0.04 is well below a typical 0.4 - 4.5 TSH reference interval.
The statment 'For an average person fT3 and fT4 will move around their mid-intervals' is somewhat axiomatic. If on average most people were '75% up through the range' the reference interval would be higher. The fT3 and fT4 reference intervals are slightly skewed but most people have values around the mid-points - you can see an example in Figure 2 here degruyter.com/document/doi/... (I haven't read this study, just grabbed it as an example.) If patients are put on levothyroxine monotherapy we can expect them to have upper quartile fT4 and average fT3 (I don't advocate this strategy).
Dr Lowe treated a subset of patients with fibromyalgia caused by resistance to thyroid hormone. Obviously in these cases supra-physiological doses of T3 are needed. We shouldn't extrapolate these special cases to the majority of patients who have primary hypothyroidism.
Dr Toft's assertion that it's OK for fT4 to go above the upper limit 'provided fT3 remains unequivocally normal' (can't remember if he said normal or in range) is pseudo science. He gives no evidence for this statement. It implies any dose of levothyroxine is safe provided fT3 is normal - this is silly some patients will be thyrotoxic. It also implies that you should never give a dose that raises fT3 above its upper limit, this would deny many patients effective treatment.
As a starting point aim for typical fT3, fT4 levels with a normal TSH. If this doesn't work then other treatment strategies are needed such as higher doses or T3. It's wrong to suggest that fT3 and fT4 should be a target for treating hypothyroidism, it will be inadequate for some patients and too much for the majority. There is no evidence to suggest specific values of TSH, fT3 or fT4 should be used as a target for treatment of hypothyroidism.
It's wrong to suggest that fT3 and fT4 should be a target for treating hypothyroidism, it will be inadequate for some patients and too much for the majority.
Think you missed a word out there, didn't you? Inbetween 'that' and 'fT3'. Otherwise, the sentence doesn't make sense.
The fT3 and fT4 reference intervals are slightly skewed but most people have values around the mid-points
You mean euthyroid people?
If patients are put on levothyroxine monotherapy we can expect them to have upper quartile fT4 and average fT3 (I don't advocate this strategy).
Why don't you advocate this strategy? Do you think people should be put straight onto T4+T3?
As a starting point aim for typical fT3, fT4 levels with a normal TSH.
To save repeating the questions I'll number them 1 to 4.
1. I should have said specific levels of fT3 and fT4 should be targets. This includes targetting upper quartiles.
2. I meant healthy people but as most of the population don't have thyroid disorders most of the population would be closer to the mid-points than the extremities.
3. I no longer advocate this strategy because of recent research linking higher fT4 with cancer (sorry I will post on this as soon as I can). I would advocate for levothyroxine only for mild cases of primary hypothyroidism where the patient feels OK on low or moderate doses. In general I think patients should be given levothyroxine liothyronine combination therapy, even if they feel OK on levo only. My view on this has changed in recent months.
4. As a frist pitch perhaps aim for a TSH around 1 or 2 and then adjust according to individual patients requirements. This is just an initial ball park figure to have a starting point definitely not a target.
1. I should have said specific levels of fT3 and fT4 should be targets. This includes targetting upper quartiles.
Once again, you've missed out a word - or, you're contradicting yourself.
2. Agreed. But that doesn't mean that nobody should be.
3. Now we're on the same page!
4. Agreed. But I think that a TSH of 2 would be too high for the majority of hypos, and it's not even average euthyroid.
BUT would you not agree that the majority of hypos need more thyroid hormone, and higher levels of FT4/3, and therefore lower levels of TSH, than the majority of euthyroids? And that you cannot compare euthyroid levels with levels in people taking exogenous thyroid hormone, as a general rule - allowing, of course, for individual needs? And that encouraging doctors to think that all they need to do is get the TSH back somewhere - anywhere - within the 'range' is wrong?
pitching for TSH around 1 or 2 as a starting point, most patients will need a TSH below 2. Certainly those on levothyroxine monotherapy will on average need a lower TSH than the average healthy person, so that they have extra T4 to compensate for the lack of T3 medication. Of course I'm now in favour of combined T3 / T4 therapy for most patients. TSH is perhaps the least accurate marker of thyroid status (but IF possible it's good to have some TSH to encourage deiodinase).
Most people on this forum will have more difficult to treat hypothyroidism and so need higher doses than the majority of patients who do fairly well on levothyroxine (not ideal but OK).
Or is it just that the majority of thyroid patients on levo monotherapy haven't found this forum?
Anyway, I'm glad to hear you say that TSH is the least accurate marker of thyroid status. You've always given the impression that you thought the opposite.
I’ve never said that TSH is a reliable marker of thyroid status. It can be useful, a high TSH is great at detecting primary hypothyroidism and cretinism. A normal TSH with low or low normal fT3 AND fT4 indicates a degree of thyrotroph (or pituitary) failure which I believe causes more severe hypothyroidism that we might expect. Endocrine disrupting chemicals can cause hypothyroidism with a normal TSH.
So, a high TSH is specific (few false positives) for primary hypothyroidism but TSH is not sensitive (many false negatives) for hypothyroidism. TSH is a useful tool but needs to be interpreted in relation to signs and symptoms and other hormone levels. It’s much better to avoid a very low TSH if you can, because of the role TSH plays in deiodinase.
All I would add is that if you have / have had Graves I would have a DEXA / REMS scan to check the condition of your bones. I had Graves some years ago and no one mentioned that an overactive thyroid can lead to osteoporosis- ten years later when I actually have osteoporosis I discovered an overactive thyroid is on a list of contributory causes of osteoporosis. Other contributors are rheumatoid arthritis, coeliac disease, early menopause, taking steroids, taking PPIs. So check now while you have time to act on strengthening your bones.
Hi Fruitandnutcase, thank you so much for mentioning this I had no idea either. Completely coincidentally I am having a Dexa Scan on Wednesday but that was because I have gone in to an early menopause (age 43) but have probably had symptoms since I was in my 20's and 30's so I am very pleased I'm having one now after what you have said. Thank you, I hope you are managing to keep your osteoporosis under control as much as you can. Thank you again, Emma x
That’s good, sounds like your doctors are looking after your interests better than mine were. I forgot about early menopause being another of the markers. I’ll go back to my post and add it in. Good luck with the DEXA 😊
I actually suggested the Dexo Scan and after reading your comments I am very pleased I did! Thanks again for the heads up, fingers crossed my Dexa Scan results come back ok
If you have Hashimoto´s and Graves´, your thyroid gland has already been damaged by inflammation. I´m curious: why would your FT4 and TSH damage your thyroid gland? The TSH only has one role - to stimulate thyroid hormone production. The T4 you are taking replaces the hormone your thyroid gland is no longer making. How could they damage your thyroid gland?
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