Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study

[helvella]

We have seen several posts where a member was told to stop taking levothyroxine in order to prove, umm, something or other. (I put it so vaguely because the very idea of removing levothyroxine that is needed is so fundamentally misconceived.)

This was a reduction of 30% among volunteers (no - I would NOT have agreed to take part). And the impact is significant.

The bit that matters is the conclusion:

The human brain seems especially sensitive to even short-term thyroid hormone changes.

Anyone here actually surprised? Nonetheless, good to see it published.

Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study

AnnaGöbela

1 Martin Göttlicha 1 Marcus Heldmannab René Georgesc Relana Nieberdingc Berenike Roggea Alexander Sartoriusd Georg Brabantc Thomas F.Münteab

Highlights

• Aim: to evaluate the effects of induced subclinical mild hypothyroidism on brain network connectivity, showing global changes of brain function.

• Method: 15 otherwise healthy hypothyroid subjects under long term levothyroxine substitution reduced their pretest levothyroxine dosage by 30% for 52–56 days. Before and after reduction, resting state fMRI, neuropsychological analysis and laboratory testing was performed.

• Results: Desired subclinical hypothyroidism was achieved.This lead to a significant decrease in resting-state functional connectivity in the cuneus. This was caused by weaker connectivity to cerebellum and regions of default mode network. The decrease of the connectivity in the cuneus was correlated to the increase in TSH serum levels. Subjects showed a longer reaction time and less accuracy in a memory task after levothyroxine withdrawal.

• Conclusion: The human brain seems especially sensitive to even short-term thyroid hormone changes. Even slight cognitive changes in subclinical hypothyroidism may be mediated by the cuneus, connected to the cerebellum, posterior and medial frontal cortex.

doi.org/10.1016/j.psyneuen....

sciencedirect.com/science/a...

[Sybilla14]

Great to see an interesting study although it is noting a correlation with TSH level and not ft3 yet again. I’m on a programme of reducing t4 dose as my ft3 has been over range since adding t3 and I feel the effects of 12.5mcg drop within a couple of days, suffering with cognitive impairment and brain fog despite the fact that my previous dose was seemingly too high. Week 5 since the last reduction and I seem to be starting to feel ok again. I doubt my TSH would have moved significantly from virtually nil.

[Wildbird]

Why would anyone undertake research which had sub clinical hypothyroidism as a desired outcome? Surely this cannot be ethical. I cannot for one second imagine research which lowers insulin for those diagnosed with diabetes being approved. The results speak for themselves. Under treatment impacts our brain and impedes our function, as we have been telling our GPs for decades. Despite this, Nice are looking to have higher TSH levels for elderly people, I despair 😩

[TSH110 in reply to Wildbird]

Nice are nasty! What gets me is that anyone might think that a lack of hormones could possibly be good for anyone be it a small lack or a large lack - it is going to cause problems. To think medical professionals don’t even see what is a basic law of nature beggars belief and claim subclinical hypothyroidism is nothing to be bothered about or treated fills me full of horror; as for virtually withdrawing thyroid replacement therapy from the elderly - no treatment till TSH over 10 😳 or even TSH over10 adopt a wait and watch strategy 🤬 what are they waiting and watching for? Death by myxoedema I presume. Having nearly been there myself it would be a hideous way to die...in fact wasn’t that the situation before there were any treatments, we just died a slow and horrible death. Modern medicine is really pushing forward the frontiers of Endocrinology right back to those of pre 1889 or was it 1898 when sheeps’ thyroids were first successfully used to treat hypothyroidism. It is euthanasia dressed up as Nice guidelines for treating hypothyroidism they should be renamed “guidelines for NOT treating hypothyroidism” . Yet we are not allowed euthanasia - a darn sight quicker than dying of untreated hypothyroidism.

It is awful that studies like this are needed to prove to supposedly intelligent people in a professional medical capacity that not having enough thyroid hormones impacts seriously on the functioning of the body and mind. Is it me or what? How could it be otherwise or any old amount of hormones would do, especially if you are old. Oh hang on that’s exactly what the Nice Guidelines imply - god help us. Who wrote them?They need removed from anything do with thyroid care they are not fit for purpose and so completely out of line with the rest of the world.

I hope more proof like this of the patently obvious is forthcoming soon.

[Wildbird in reply to TSH110]

You put it so well and it’s so worrying because we will all be old if we are to continue living. Quality of life for the elderly is clearly low down on the list if you fall into the over 65 category, despite most of us having to work. Until we are 68-70! Perhaps we need some kind of Thyroid Union to swamp the medics, in respect of their ignorance. Most of the “research” they treat us by, have ill conceived abstracts, with dubious conclusions. Nice still bangs on about osteoporosis and atrial fibrillation if tsh is low. They ignore the fact that thyroid hormones control and regulate our heartbeat. If they added t3 to make up for some people’s shortfall, they may be amazed at the results. Thankfully we are not fooled! 🤔

[TSH110 in reply to Wildbird]

Yes good point about having to work till we drop with millions effectively stolen from women by suddenly pulling the pension rug from under us it is not as if there was even pay equality when I first started working either. I believe in Germany the have reversed the increase in pension age because it does not make good economic sense. How I will keep going to 67 I don’t know I do a hard physical job very long hours plus a long commute. If I get any serious physical health probems i’ll be finished I worry about that quite a bit. Then to think of those appalling Nice guidelines punishing you for your age when there is no evidence that older people need less thyroxine - you tend to need what you always needed more or less (I actually need more than I did for the first three years) according to studies I think Humanbean has mentioned here. Older people did not have huge TSH readings compared to everyone else they were pretty similar. Where they dredge this half baked rubbish up from I just don’t know - the depths of their predjuduced minds seems like a good bet! They probably used a load of old people with untreated overt hypothyroidism to get the “normal” range. It looks like it is the reason for a lot of dementia and heart disease and probably a whole lot more ilnesses. Dreadful really.

[MaisieGray]

A good find. For me, the particularly important issue is the effect on the cuneus, given its function, which have a number of potentially wide ranging different implications. For expediency, I copy from Wiki: " The cuneus (Latin for "wedge"; plural, cunei) is a smaller lobe in the occipital lobe of the brain. The cuneus is bounded anteriorly by the parieto-occipital sulcus, inferiorly by the calcarine sulcus. The cuneus receives visual information from the same-sided superior quandrantic retina (corresponding to contralateral inferior visual field). It is most known for its involvement in basic visual processing. Pyramidal cells in the visual cortex (or striate cortex) of the cuneus, project to extrastriate cortices. The mid-level visual processing that occurs in the extrastriate projection fields of the cuneus are modulated by extraretinal effects, like attention, working memory, and reward expectation. In addition to its traditional role as a site for basic visual processing, gray matter volume in the cuneus is associated with better inhibitory control in bipolar depression patients. Pathologic gamblers have higher activity in the dorsal visual processing stream including the cuneus relative to controls."

[helvella in reply to MaisieGray]

So, we are led to ask, is there any connection between thyroid levels and pathologic gambling?

[MaisieGray in reply to helvella]

Well yes, good question. I was thinking more about the bi-polar connection, and attention deficit disorders, and regarding the visual processing aspect, potential obstructions to how people/children learn.

[SilverAvocado in reply to MaisieGray]

I came across the term 'executive function', and realised it captured very well something I notice myself and my hypo friends being deficient in.

This covers things like seeing the big picture, making the connection between the small tasks that will accomplish a large task, awareness of time passing, the consequences of actions, planning and then following the plan, etc etc.

Sounds a bit similar.

[TSH110 in reply to SilverAvocado]

Blimey almost exactly what I have just emailed to a friend describing this very problem!

[Hillwoman in reply to SilverAvocado]

Very interesting remarks SilverAvocado I've noticed the same problems in myself (of course) but also in my father-in-law, who is now 85. Several years ago he was told his thyroid function was 'low'. It remains untreated, and this very intelligent man's executive function has declined markedly. His family are trying to clean up the fallout from his uncharacteristically poor judgment, but what he really needs is thyroid hormone replacement. He won't challenge his doctors though - a common attitude in others of his generation.

[SilverAvocado in reply to Hillwoman]

Interesting. Its good to hear that other people have noticed a similar thing.

[Hillwoman in reply to SilverAvocado]

Sorry, I missed the fact it was your comment I replied to. Corrected now.

[SilverAvocado in reply to Hillwoman]

Its interesting how you say this is a different thing from intelligence, even though in common sense terms it would be seen as part of intelligence.

Both my hypo friends who don't really take care of themselves are very bright but always have this air of confusion around them. They don't quite know what they're doing here or where they're going next. Or, more sad, they don't really have a handle on their hopes and dreams and who they want to be as a person.

The thing I notice the most in myself is it takes me double the time to do almost any task. I have to start getting ready for bed about 4 hours before I turn the light off! I only really notice the sense of control and mastery over things when I get an improvement with a dose increase. Being able to keep track of things like what food I have in my fridge, or who the characters are in a film.

[Hillwoman in reply to SilverAvocado]

I take your point - these are all aspects of a person's intelligence, which should perhaps be considered in the round. The late Dr Spurr (ME researcher) told me about IQ tests he ran on a few of his patients who happened to have pre-illness scores. I can't remember the average percentage drop in IQ, but it was pretty frightening. His point was that some chronic illnesses measurably reduce a person's intellectual ability. (Then again, IQ score is just one aspect of intelligence!)

Perhaps what I should have said is that my father-in-law seems overall to be a less intelligent person than he was a few years ago, because of the decline in executive function. He is Cambridge educated and was a senior lecturer in applied maths. He retired at 54 to care for my late MiL, and after her death he was involved for many years in a research project relating to his field (please don't ask me what that was ). I'd always suspected that he was somewhere on the autism spectrum, and that impression was heavily reinforced by a recent encounter with him. So I decided to read up on autism in adults, and realised I'd got this all wrong. Now, I think his fundamental problem is chronic 'sub-clinical' hypothyroidism, and possible B12 deficiency too. As a family, we're just now seeing some of the long term consequences of non-treatment.

[SilverAvocado in reply to Hillwoman]

Wow, very interesting that you thought it was autism spectrum.

With intelligence it's an interesting question. I feel like deep inside I am as smart as I was before my illness, but there are a lot of on the spot quickness things I know I can't do, and I can't follow technical talk at all, even someone describing a train journey plan. I also don't have the concentration to read much or follow a film.

I wish I had access to a lot of cognitive testing, not only of IQ but things like word recall, reaction and accuracy and all of that, some of the more far out ones they do for neurological patients like copying a drawing. I'm sure the results would be very interesting and vary in interesting ways with how I've been on different doses. I think it would give the 'proof' of exactly how sick we are just as much as the complex metabolic tests that show how much oxygen you use and things like that.

[Hillwoman in reply to SilverAvocado]

I hope you don't think I was implying an automatic intelligence deficit in people with autism. 😟I didn't want to say too much about FiL's personality, but I've always found him a very challenging person to be with in terms of his poor interpersonal skills, which in recent years have really deteriorated, alongside certain aspects of his judgement and his obsessive behaviour.

[SilverAvocado in reply to Hillwoman]

Oh no, I didn't think that at all. I thought it was interesting because I recognise a similar thing in people I know. That the confused, not quite judging things right can come out as being a bit oblivious to others around them (us) and not understanding all the social cues, or how to join in with others.

[Hillwoman in reply to SilverAvocado]

It would be so interesting to read some in-depth research on these wider, more social aspects of hypothyroidism, but this sounds more like the sort of thing your profession might do, rather than the medics.

[SilverAvocado in reply to Hillwoman]

Fingers crossed I will get there one day

[TSH110 in reply to helvella]

Give it is more prevalent in those with bipolar (risk taking) and bipolar seems to be somehow related to thyroid function, I think it quite possible there could be a link

[Hidden]

Thank you, fascinating and helpful! Relevant to the present situation with my eyesight too. But they didn't say if the effects wore off when the volunteers went back to their normal replacement dose.

Pity about the TSH, but for the purposes of the study I suppose measuring that was better than nothing

[helvella in reply to Hidden]

We should be able to assume that they did return to their pre-study states. But I am not convinced that we can safely do so. Any period of inadequate thyroid hormone seems capable to inflicting damage which takes a long time to reverse, if ever it does.

That is half the reason I absolutely would not have volunteered for this study. The other half is unwillingness to have been under-dosed for two months.

[Hidden in reply to helvella]

Exactly!

[SilverAvocado in reply to helvella]

This study reminds me of the time, as a graduate student, I took my literature friends to a psychology talk.

Their comment on it? "Oh, so psychology is all about torturing rats?".

[TSH110 in reply to SilverAvocado]

I always feel sorry for those poor rats when I read papers about research into thyroid disorders knowing how much they must have suffered. Even more so when many of us are still suffering unnecessarily...then I wonder for what purpose have all those animals been tortured? Is it to satisfy a bunch of psychopaths getting their kicks whilst they pose as scientists?

I hope they are not suffering and dying in vain but with thyroid disorder treatment seemingly going backwards I am not convinced their sacrifice is of any medical value whatsoever.

[TSH110 in reply to helvella]

I thought effects would be reversible quite a shock to see that may not be the case. It might explain why I am still such a mess 😂🤣😂 I was was a lot more hypothyroid than that for decades.