How does synthetic t4 convert to the active t3 ... - Thyroid UK

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How does synthetic t4 convert to the active t3 after a thyroidectomy?

Litatamon profile image
22 Replies

Is it the same place & way if one still has their thyroid? Ie. When you all note that hormones given replace the thyroid, not top it up if the thyroid is still in place, does it then not matter if one has a thyroid for this mechanism? (Not discussing taking anyone's thyroid without obvious dire need , just curious about processes and differences) Does it occur in multiple organs in the body? Does hormone replacement tax those organs any more with non-naturally occuring hormones as opposed with the process from a healthy functioning thyroid?

I think I read this from someone last week but does synthetic t4 also produce t2 and t1 somehow in the body with no thyroid?

Thank you. I am sure some of my inquiries are without the proper terminology and mechanisms listed, I am just free- flowing with curiosities.

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Litatamon profile image
Litatamon
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22 Replies
jimh111 profile image
jimh111

The short answer is yes except the thyroid converts and this conversion is this lost. In addition if levothyroxine only is used a higher fT4 is needed to compensate for or the loss of T3 from the thyroid.This results in a lower TSH with more type-1 (D1) deiodinase and less type-2 (D2) deiodinase. D2 converts T4 to T3 close to nuclear receptors in tissues such as the brain and skeletal muscles whereas D1 does it on the cell membrane in organs such as the liver and kidneys.

Most people don't notice the difference but studies show that those who inherit a DIO2 polymorphism from both parents suffer minor cognitive impairments.

T2 and T1 are derived from T3, so since levothyroxine treatment gives similar T3 levels it shouldn't make a difference.

Litatamon profile image
Litatamon in reply tojimh111

Thank you Jim. That last paragraph was exactly one part that I have been trying to understand.

Inna profile image
Inna

If I remember my research correctly, most of the conversion happens in the liver. Though no matter how much I tried to improve my conversion rates by improving my liver function, the blood tests show the same low conversion rate as always.

Litatamon profile image
Litatamon in reply toInna

Thank you Inna. Hope you have found your sweet spot.

jimh111 profile image
jimh111 in reply toInna

It used to be asserted that most conversion occurred in the liver but this is not so. Usually most conversion is fone by type -2 deiodinase in tissues such as the brain, skeletal muscles and brown fat. The thyroid also converts some T4 to T3 along with the skin, liver and kidneys.

Inna profile image
Inna in reply tojimh111

Thank you. I was researching that quite a bit ago, so it might be out of date currently.

Bilbobaggins55 profile image
Bilbobaggins55

My understanding is not. You have to take the active hormone T3 - some people do not convert T4 even when they have a thyroid & take T3. But it’s difficult to get in uk - Canada are probably more progressive. Good luck.

Litatamon profile image
Litatamon in reply toBilbobaggins55

Thank you Bilbobaggins55.

SlowDragon profile image
SlowDragonAdministrator

For good conversion we need good vitamin levels

Good vitamin D, folate, ferritin and B12

What vitamin supplements are you taking

When were vitamin levels last tested

See on post 2 months ago you are currently taking Erfa

Have you increased your dose

healthunlocked.com/thyroidu...

Litatamon profile image
Litatamon in reply toSlowDragon

Hi SlowDragon,

Thank you as always for your knowledge and care. This post is not really directly about my case, I am just curious how the body does the conversion & if or how the mechanisms change without a thyroid.

But thank you again.

helvella profile image
helvellaAdministrator

Conversion of T4 to T3 takes place in numerous tissues of the body.

The widespread claims that it is done in the liver, maybe kidneys, sometimes other tissues is sort-of true but potentially misleading.

Those tissues convert T4 to T3 and release at least some of that T3 into the blood stream to be carried round the rest of the body in significant quantities.

But many other tissues can convert T4 to T3 for use within those cells/that organ. For example, hair follicles.

And the brain is a whole extra layer of complexity - within which specialised cells convert T4 to T3 for local use.

Lack of thyroid does remove the possibility of thyroid tissue converting T4 to T3. Yes, that is significant. But most conversion takes place outside the thyroid.

And you have to consider the lack of direct production of T3 by the thyroid.

I would ignore T2 and T1. There has been many mistakes regarding T2 and T1 being produced by the thyroid.

Litatamon profile image
Litatamon in reply tohelvella

'I would ignore T2 and T1. There has been many mistakes regarding T2 and T1 being produced by the thyroid.'

Thank you helvella.

Could you expand for me please

Does this mean that the pushing that NDT contains all the thyroid hormones (meaning t2 and t1) is overhyped for health?

helvella profile image
helvellaAdministrator in reply toLitatamon

In my view, grossly overhyped.

In the thyroid, iodine is attached to the amino acid tyrosine to produce two intermediates: 3-iodotyrosine (also called monoiodotyrosine or MIT) and diiodotyrosine (DIT).

Then two DIT molecules can be joined to produce T4. Or one MIT plus one DIT to produce T3.

But I have seen several documents over the years where MIT is talked about as being T1, and DIT as T2. Which is a fundamental error.

Something like “’mono’ means ‘one’ so that’s T1 and ‘di’ means ‘two’ so that’s T2”.

The thyroid will always have some MIT and DIT (simply because they are intermediate compounds) as well as some T3 and T4. But there’s nothing obvious to suggest that T1 and T2 will be present.

I can’t say there won’t be any T1 or T2 at all. There might be some. But I think the amounts will be tiny.

TSH110 profile image
TSH110 in reply toLitatamon

I’m sure diogenes felt they may have some merit, T2 at least

pennyannie profile image
pennyannie

Hello Litatamon :

In short - with difficulty - if you are prescribed T4 monotherapy and dosed and monitored on a TSH to be in the range -

rather than dosed and monitored on Free T3 and Free T4 levels - with a view to balance both thyroid hormones within the ranges at around a 1/4 ratio T3/T4 or where the patient experiences the relief of symptoms of hypothyroidism.

" I " and my cognitive functions were slowly ' rubbed out ' whilst on T4 monotherapy -

I only know this as when I introduced a little T3 alongside a reduced dose of T4 -

I had that ' light bulb ' moment you read about and it was as if my brain had been switched back on.

A fully functioning thyroid would be supporting you on a daily basis with trace elements of T1, T2 and calcitonin plus a measure of T3 at around 10 mcg plus a measure of T4 at around 100 mcg :

So you could argue that people with some thyroid function have at least a better chance of being well on T4 monotherapy as they are getting some production of the natural active hormone - T3.

T3 is the active hormone and said to be around 4 time more powerful than T4 which is inert, a prohormone, and needs to be converted in the body into T3.

Converting T4 into T3 needs optimal levels of core strength vitamins and minerals - viz - ferritin, folate, B12 and vitamin D and conversion can also be down regulated by inflammation, antibodies, any physiological stress ( emotional or physical ) depression, dieting and ageing.

Try making a scone with plain flour - it 's hard going and more of a doorstop -

add a little baking powder - lift the flour - and now your baking takes off :

Litatamon profile image
Litatamon in reply topennyannie

Thank you pemnyannie. Really helped me understand the process.

TSH110 profile image
TSH110 in reply topennyannie

Mine was like a missing piece of a jigsaw fell back into place and I was complete again. T4 monotherapy left me fat, miserable, stupid and two dimensional like I was some sort of shadowy thing, it was deeply unpleasant. NDT changed all that and I got my life back, yet we struggle to get hold of it, it’s criminal.

Oddly my relatives with thyroid disorder feel/felt great on T4 monotherapy so mine must be a conversión issue, may be it’s down to having a different thyroid disorder one had total thyroidectomy for an abnormal lumpy thyroid going into the chest another had emergency chemo for a huge life threatening goitre I don’t know about the details of the other two, but mine just atrophied away I never had a goitre or something genetic I have one allele for poor conversion in DIO2.

TSH110 profile image
TSH110

This is quite a detailed explanation by Dr Tania Smith:

thyroidpatients.ca/2018/07/...

Her blog posts can be a challenge but they are worth reading. There are lots now all are very good.

pennyannie profile image
pennyannie in reply toTSH110

So you're not impressed with my cooking analogy or you just don't like scones ?

I have a see- saw analogy as part of my repertoire - I may part with next time ;

TSH110 profile image
TSH110 in reply topennyannie

They have to be GF 🤣🤣🤣

pennyannie profile image
pennyannie in reply toTSH110

Oh - shucks !!!

Litatamon profile image
Litatamon in reply toTSH110

😁

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