Partial withdrawal of levothyroxine treated disease leads to brain activations and effects on performance in a working memory task

[helvella]

I suspect many here will add this to the "state the obvious" collection of papers!

Is anyone reading this in the least surprised by the impact? Certainly the backing up of performance by fMRI adds to the study as compared to our personal experiences and that is good.

However, I do think it is important that what we might consider absolutely day-follows-night should, so far as possible, be backed up with properly conducted studies.

(I have deep reservations as to the ethics of this study. Is it right to knowingly reduce a life-sustaining medicine sufficiently to have significant effects on the subjects?)

J Neuroendocrinol. 2019 Mar 15:e12707. doi: 10.1111/jne.12707. [Epub ahead of print]

Partial withdrawal of levothyroxine treated disease leads to brain activations and effects on performance in a working memory task: A pilot study.

Göbel A1, Heldmann M1,2, Göttlich M1, Georges R3, Nieberding R3, Sartorius A4, Brabant G3, Münte TF1,2.

Author information

1 Department of Neurology, University of Lübeck, Lübeck, Germany.

2 Department of Psychology II, University of Lübeck, Lübeck, Germany.

3 Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.

4 Central Institute of Mental Health, Mannheim, Germany.

Abstract

BACKGROUND:

Hypothyroidism is associated with memory impairments.

OBJECTIVES:

The aim of this study was to evaluate the effects of partial withdrawal of levothyroxine on working memory tasks and brain function.

METHODS:

Fifteen subjects under long-term levothyroxine substitution due to complete hypothyroidism participated in this study. A functional MRI was performed using a working memory task (n-back task) and neuropsychological tests were performed before and 52-54 days after the induction of subclinical hypothyroidism by reducing pretest levothyroxine dosage by 30%.

RESULTS:

Reaction time of subjects under partial levothyroxine withdrawal was significantly longer and less accurate in solving the working memory tasks. FMRI revealed significant activation changes after medication withdrawal in the cerebellum, insula, parietal, frontal, temporal and occipital lobes, lingual gyrus and the cuneus.

CONCLUSION:

Partial withdrawal of levothyroxine may lead to deficits in a working memory task and to an activation of brain areas associated with working memory ability. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

fMRI ; Hypothyroidism; memory; n-back task; thyroid

PMID: 30875138

DOI: 10.1111/jne.12707

ncbi.nlm.nih.gov/pubmed/308...

Added 14:52 16/03/2019

Access to the full paper (and many others) by free registration: neuro.uni-luebeck.de/neuro/...

[Baobabs]

A very interesting study Helvella and yes a bit of state the obvious which makes one wonder why anybody would wish to spend money on it in the first place. This is especially bearing in mind how many other more pressing research needs to be done in the field, such as those who don’t convert for whatever reason, the need for sound studies looking at the effects of low and high blood serum levels of Thy stim hormone on the heart and bones, thyroid hormone resistance and so on. One would also wonder where in that magical range their blood serum thyroxine was as according to many medics, anywhere there is just fine. What evidence do we have they were optimally medicated in the first place for lowered doses to make that much difference? Thanks and of course as research in this field appears thin on the ground, all research is of interest to most with thyroid anomalies.

[Hidden in reply to Baobabs]

Exactly!

I can't resist commenting on "Thy stim hormone"? Dost thou possess one? Not sure if I do or not

[Baobabs in reply to Hidden]

Hello, I have to write it like this as when I use my iPad, it comes out like this - T-shirt! These gizmos have a mind of their own.

[Hidden in reply to Baobabs]

Words, and the strange things can happen when they aren't quite right are fascinating. Had a real chuckle when a friend messaged me. She was talking about making a drink using ginger. She meant to say "I mash up my ginger with a pestle and mortar. Instead she wrote "I mash up my FINGER..."

Another time, when in work on a quiet warm afternoon, someone jokingly accused one of the staff of sleeping. He said "I'm not, I'm alert. From then on he was called "The Lurt"

A bit of comic relief goes a long way!

[Hidden in reply to Baobabs]

And when I was working abroad I asked someone where another person was and they said "She's in the chicken". Never noticed before how similar it is to "Kitchen" - especially when English isn't your first language.

[Baobabs in reply to Hidden]

Tell me about it! Confusion ‘reigned’ and we all got wet!

[Hidden in reply to Baobabs]

It works the other way around too. I learned a smattering of the local language, and if we were going out, tried to ask the lady who worked for us not to cook supper. She always looked puzzled though got the message. I found out eventually that I was actually saying "You NEVER cook supper"

[Baobabs in reply to Hidden]

Let’s hope she possessed a heart of gold.

[Hidden in reply to Baobabs]

Oh she did! Very tolerant of us foreigner's funny ways

[Hidden in reply to Baobabs]

Just one more joke, a ditty I read:

"The rain it raineth every day

Upon the just and unjust fella.

But mostly upon the just because

The unjust hath the just's umbrella."

[Hidden in reply to Baobabs]

I really am slow, only just got this!!!

[MaisieGray in reply to Baobabs]

That is seems to prove what patients already know or believe to be so, doesn't thereby invalidate the study. Possibly/probably quite the opposite, I'd say. If patients frequently self-report that they feel worse, or functioning deteriorates, when their Levo dose is reduced, it makes great sense not only to test it out in a controlled environment, but to identify/qualify/quantify what exactly is being affected by the reduction. Not only does direct imagining of the brain eliminate problems that Drs must often experience in interpreting exactly what symptoms the patient is describing - "I dunno, my brain just feels fuzzy" for instance - but presumably also rules out distortion inherent in a patient's personal and subjective assessment of what they are experiencing. Not to mention the obvious conundrum, that asking someone to think about exactly how their brain isn't functioning as well, in a certain situation, as it normally does, may mean that perhaps they aren't always the best person to ask. And of course, the study allows for comparisons to be made to identify if the effects are the same for every patient, and if not, why not. And so much more. In principle, a useful study, to my mind.

[Hidden in reply to MaisieGray]

Yes, useful indeed. I suppose it's still very annoying that they have finally caught up with what we have been trying to tell them for years!

[Baobabs in reply to MaisieGray]

I didn’t say the obvious conclusion invalidated the study. It would be interesting to know what thinking initiated the study. You are correct in saying that many folk suffering with brain fog are regarded with scepticism. Something that is not easily measured other than by MRI scanning.

[Hidden in reply to Baobabs]

I don't think anyone thought you meant that x

[Hidden in reply to Baobabs]

It's hard to forget one doctor on the phone who told me I was "Confused" because I was struggling to explain my symptoms while barely able to put a sentence together.

[Baobabs in reply to Hidden]

Yes, it seems to suit medics to pick and choose from the list of symptoms when we are feeling wretched in the ‘confession box’ It’s an incredibly vulnerable place to be and one where their list of possible symptoms seem to be infinitely more succinct and clear cut than ours. Talking from the same page seems an illusive impossibility.

[Hidden in reply to Baobabs]

I put my foot in it recently, and it was quoted on my notes to "Prove" I'm over-medicated! I tried to explain a sort of wobbly unstable feeling. It felt as if my legs didn't have the strength to support me steadily. It felt as if I wouldn't be able to keep balance trying to walk across the room. But I used a different word - "Shaky" probably, so it was assumed it was a hyper symptom!

[Baobabs]

Perhaps the purpose of the study is to save money? Why, however when Levo is cheap as chips?

[Pascha1 in reply to Baobabs]

I think you could be right on that, test on lower doses if ok lower everyones dose,, was it run by the CCG NHS the study ?

[helvella in reply to Pascha1]

It is a German study.

There is only partial correlation between dose and cost.

For example, a 100 microgram tablet is cheaper than either a 75 microgram tablet, or 50 and 25 tablets to make up 75 micrograms. In that case, dose reduction would increase cost. Similarly, 200 micrograms would be less expensive than 175 micrograms. It is purely luck which determines how many tablets an individual needs for their dose and how expensive they are.

Reducing all doses by 25 micrograms across the board might have little impact on cost.

[Baobabs in reply to helvella]

Levo is cheap to produce.

[helvella in reply to Baobabs]

Yes, the tablets are cheap to produce. Even the cost to the NHS is low. But unless there is a feasible saving, I cannot see any possible reason for postulating that there is an aim of achieving a blanket reduction.

[Baobabs in reply to helvella]

Perhaps they were researching aspects of impaired mental health? Strange a reason is not given,

[helvella in reply to Baobabs]

They do give a reason - go and get the full paper:

Our rationale to perform this study was to evaluate changes in comparison to our prior experimentally induced hyperthyroidism study. To the best of our knowledge, this is the first study published examining subjects after experimentally induced hypothyroidism. This is especially important, since there is still a debate in the literature whether subclinical hypothyroidism leads to cognitive changes, showing that further studies are needed. We hypothesized that mild hypothyroidism may affect functional connectivity, most likely in the same regions altered in hyperthyroidism.

[Baobabs in reply to helvella]

Experimentally induced hypothyroidism?

[helvella in reply to Baobabs]

By reducing levothyroxine dose.

[Baobabs in reply to Pascha1]

It’s some government associated body ........ Say no more.

[helvella in reply to Baobabs]

The study was from the University of Lübeck, Lübeck, Germany and Central Institute of Mental Health, Mannheim, Germany.

Not sure what you mean by some government associated body?

[Hidden]

VERY interesting, and so obvious for all who suffer with thyroid problems. I agree it's completely unethical to make people suffer brain fog - even assuming they volunteered.

[Baobabs in reply to Hidden]

In the UK from what I gather most folk with thyroid disease seem to be regarded as lab rats.

[TSH110 in reply to Baobabs]

Making us suffer from brain fog is popular with medics of you ask me 😬

[Baobabs]

Also a very small study which adds to both its usefulness and validity.

[Pascha1]

They didn't need to waste money doing a study by reducing meds on purpose!

They only had to check all people with Hypothyroid at Drs surgery's and they would quite easily found many Hypothyroid patients who are suffering with severe brain fog.and loss of brain function from being left under medicated...

Really they should be doing something to help us b trialing NDT or T3 and get some proper evidence out thats long over due to how well most do on NDT ,T3 combo and T3 mono rather than T4 mono reducing it...

Maybe give them something to help them start thinking and doing something useful!

[RedApple in reply to Pascha1]

Pascha1, You do of course have a point about all the under-medicated thyroid patients at Doctors surgeries. The problem with that though, is there is no 'before and after' info. So nothing to prove that on the correct dose, we are bright, intelligent and much less forgetful, as opposed to severely brain fogged on the incorrect dose. When we're in front of the doctor in an under-medicated state, it's generally assumed that we're just [mostly] menopausal, [mostly] middle aged, [mostly] women who never had a fully functioning brain in the first place

[helvella in reply to RedApple]

There are MANY menopausal, middle aged, women who have fully functioning brains - at least, once their thyroid hormone levels are corrected, if needed.

Any assumption that anyone in any or all those categories automatically does not have a fully functioning brain is just that, an assumption, and an unwarranted one at that.

However unwelcome and untrue, it is, I absolutely agree, far too often an assumption that is made, a label that is applied, a travesty instituted.

[Pascha1 in reply to RedApple]

I was put on HRT last year 15 years after my menopause had stopped aged 54 , I had given the GP a list of my symptoms he took one look and said oh you need HRT,, I am now told by the endo I should not of been given Hot after I was 45, , I am scared to come off it now as I will have to go through change again which is the last thing I want to be doing,,

I did get better Gp after him and she reckonised my symptoms were hypo sympmtoms and have T3 added t which was much better, and in middle of switching over to NDT but early days on that one,, but after 36 afetr thyroidectomy I am getting the treatment I should of had years ago,,, and getting that was a fight even though endo and GP on side I hhad CCG clinical pharmacist trying to stop all that,, but stayed strong and pestered the life out of the and they buckled lol x

[TSH110 in reply to Pascha1]

The idea of HRT is to mask the menopause so you take it until it has ended to escape some of the unpleasant symptoms it can cause...which are also very similar to those of hypothyroidism hence one of the reasons for the high levels of misdiagnosis. You should not have another menopause if you stop the HRT as it cannot be masking anything, you will most likely feel a lot better. I was on it for far too long because I believed my symptoms were menopausal not hypothyroidism as I had first suspected but been told repeatedly was just the menopause. I immediately felt better on stopping it but the hypo symptoms persisted so I knew it could not be anything to do with the menopause. I hope stopping HRT proves straightforward and helpful to you.

[TSH110 in reply to Pascha1]

Perhaps this is not the so in Germany if they treat sub clinical hypothyrodism early, which I believe is the case

[Pascha1 in reply to TSH110]

i was diagnosed hypo just over 15years ago i think the levothyroxine put me into early menopause t 40 yrs old , so gp knew i was hypo at the time

[TSH110 in reply to Pascha1]

Mine started around that age. I thought it was correlated to the start of menarche ie the earlier periods start the earlier the menopause begins. I do not know what effect levothyroxine might have on provoking it early. I did not get treated for hypothyroidism until I was in my 50’s.

[Pascha1]

instead of blaming HRT, they need to be doing all the right tests if hypo like sex hormones SHBG that can tell quite a bit if the thyroid meds are getting into the cells,, genetic testing many things they should do instead of blaming menopause for all as in my case it wasnt that at all but they dont seem to care they just fob people of with age, etc and its really not fair when you are that patient who isnt getting on with the mono T4..,, They are definitly not taught about NDT or t3 at medical school so many drs are left ignorant on hypothyroid,

[radd in reply to Pascha1]

Pascha1,

There is no test that confirms T3 is getting into the cells, but only indicates there is a better chance.

Testing SHBG is vital when medicating thyroid hormone replacement and HRT, as elevated levels may bind a proportion of thyroid hormone rendering it inactive.

Elevated SHBG also indicates oestrogen has risen too. Useful when supplementing it. 🙂

[Pascha1 in reply to radd]

my gp said she can see by my shgb if my thyroid treatment was getting into cells,, high shgb is hyperthyroid low is hypo.. my gp now is very good

[Baobabs in reply to Pascha1]

What is SHBG?

[Hidden in reply to Baobabs]

coincidence, I just looked it up! medlineplus.gov/lab-tests/s...

Test for sex hormones but one of them can affect thyroid levels as well

[Hidden in reply to Baobabs]

"If your SHBG levels are too low, it can be a sign of:

Hypothyroidism, a condition in which your body doesn't make enough thyroid hormones

Type 2 diabetes

Overuse of steroid medications

Cushing's syndrome, a condition in which your body makes too much of a hormone called cortisol

For men, it can mean cancer of the testicles or adrenal glands. Adrenal glands are located above the kidneys and help control heart rate, blood pressure, and other bodily functions.

For women, it can mean polycystic ovary syndrome (PCOS). PCOS is a common hormone disorder affecting childbearing women. It is one of the leading causes of female infertility.

If your SHBG levels are too high, it can be a sign of:

Liver disease

Hyperthyroidism, a condition in which your body makes too much thyroid hormone

Eating disorders

For men, it can mean a problem with the testicles or pituitary gland. The pituitary gland is located beneath the brain and controls many body functions.

For women, it can mean problem with the pituitary gland, or Addison disease. Addison disease is a disorder in which the adrenal glands are not able to make enough of certain hormones."

[TSH110 in reply to Pascha1]

I totally agree.

[TSH110]

A lot of obvious things appear to be little understood by the medical profession especially in the area of the thyroid gland, if you ask me!

[Pascha1 in reply to TSH110]

Yes I agree and by them not learning these things can make people very ill and get treated for wrong conditions,, I wonder if it will ever change the ignorance on most things to to with the Thyroid,, If they are not willing to learn We should a;; be given a leaflet on all the things that could be tested should one not feel well on the treatment they get meaning T4 mono,, as really isnt fair on us who are left to suffer from ignorance of many GPS and Endos..