Role of hepatic deiodinases in thyroid hormone homeostasis and liver metabolism, inflammation, and fibrosis

[helvella]

A review of deiodinase enzymes in the liver.

For people like us, even a decent review is hard enough! But a lot easier than working our way through the original papers.

Role of hepatic deiodinases in thyroid hormone homeostasis and liver metabolism, inflammation, and fibrosis

in European Thyroid Journal

Authors: Eveline Bruinstroop, Anne H van der Spek, and Anita Boelen

DOI: doi.org/10.1530/ETJ-22-0211

Volume/Issue: Volume 12: Issue 3

Article ID: e220211

Online Publication Date: 13 Apr 2023

Abstract

Thyroid hormones play an essential role in regulating whole-body homeostasis. Deiodinases are known to convert thyroid hormone from the prohormone thyroxine (T4) to the bioactive hormone tri-iodothyronine (T3) and convert both T4 and T3 toward their inactive metabolites 3,3’,5’-tri-iodothyronine (rT3) and 3,3’-di-iodothyronine (3,3’-T2). Deiodinases are thus important for the regulation of intracellular thyroid hormone concentrations. This is known to be crucial both during development and adult life in regulating thyroid hormone-related gene transcription. This review discusses the importance of liver deiodinases in determining serum and liver thyroid hormone concentrations, liver metabolism and liver disease.

Keywords: thyroid; liver; deiodinases; metabolism; hepatitis; NAFLD

Open access including downloadable PDF:

etj.bioscientifica.com/view...

[BB001]

Thank you Hellvella I lost concentration part way through, which is a shame as it's good. I found this bit interesting: 'differences in humans and mice exist between the half-life of T3 (humans T3 1 day, mouse T3 0.45 day; humans T4 5–9 days, mouse T4 0.5–0.75 days)'.

I'm not sure I agree with it. From my experience my T3 dose starts wearing off after 4 hours. I'm wondering how does this fit with their statement that T3 has a half life of 1 day?

[helvella in reply to BB001]

Even the most interesting things can send us to sleep!

Remember, half-life is a technical concept. If you took a 20 microgram tablet at, say, 06:00, you (sort-of) have 10 micrograms left the next morning at 06:00. But the rest of the T3 in your system would also have dropped.

It would be very interesting to see continuous T3 monitor of you, as an individual.

And how we feel doesn't always exactly parallel blood levels!

[BB001 in reply to helvella]

Reading this, I got the impression that the researchers thought Dio2 was the main method for converting T4 to T3. In which case, I would love to know why, when I have normal Dio2, but homozygous Dio1, I have a conversion rate of around 0.16 (0.20 if I stick to a very restricted diet that contains no foods I'm allergic or intolerant to).

[BB001]

I'm wondering how the half life of T3 is calculated. Is it an average that hides wide variability? Is this half life a notional value calculated outside of the body, that is influenced by others factors in an individual's body? I suspect clearance rate via Dio3 could pay a part.

Are you aware of any research that shows the half life of T3 varies between people?

[helvella in reply to BB001]

For many medicines, substances which do not exist in the body, and are eliminated unchanged (or after some simple reactions to something else that does not exist in the body), it is fairly straightforward to deliver a dose, then repeatedly measure how much is left. Maybe, how much is in the urine, sometimes using a special version labelled with a radio-active tracer.

But for thyroid hormones, it is much more a case of intelligent estimation.

This is one paper:

Single Dose T3 Administration: Kinetics and Effects on Biochemical and Physiologic Parameters

ncbi.nlm.nih.gov/pmc/articl...

[BB001 in reply to helvella]

Thank you!

[helvella in reply to BB001]

Far more comprehensive and helpful, Thyroid Patients Canada (as so often!).

LT3 monotherapy withdrawal: Clearance and effects

thyroidpatients.ca/2020/06/...

[arTistapple]

Only just come across this. In my (short) experience of T3 I would like to say something about it’s so called half life. Half lives are continuous. Half life here of T3 gives the impression of an abrupt end to its effects. I have found this to be questionable. If ‘half life’ means anything like ‘radio active’ half lives, which continue to have effects even as the half lives reduce over time (from what I can remember about basic science).

Such is the utter necessity within the whole body’s chemistry for T3 - it is such a basic need to our whole metabolism - that it ‘likely’ sets off a whole other chain reaction of biochemical necessaries when taken, which are more longer lasting. So yes it may have an initial half life of itself, to which it’s effects may only be ‘felt’ for four hours (even that, from my own experience I find myself disagreeing with) whilst it sets off other biochemical reactions not necessarily which can be ‘felt’ but can be observed over time. Changes which may not become more ‘permanent’ without more T3 but remain on a longer term basis than the four hours or so of the initial half life.

I believe I have observed this in myself because I was unable to continue the T3. Some effects have been noticed/observable up to weeks after its alleged initial short duration. Another reason dosage should be carefully thought about. Tiny tiny doses might be powerful enough, especially starting T3.

In fact some forumites talk about the continuing benefits of long term thyroid meds (T3) - years later in some cases.

Thank you for ‘half lifing’ me and helping me think through and articulate things and giving me somewhere to say it - even if I am wrong!

So little research into T3.

[helvella in reply to arTistapple]

The half-life of something much simpler, glucose, is variously reported at around 25 to 35 minutes.

But that is just how long it hangs around in the blood as glucose.

It could get taken into cells and used as energy. But the moment a molecule gets taken into a cell, it is no longer in the blood so reduces apparent half-life.

It could get taken into cells and converted - eventually - via glucagon, etc., into fat. And stored for years!

It could get extracted and end up in urine.

And we all know that we don't suddenly run out of all energy within an hour or so of consuming a source of glucose.

Glucose is much easier to appreciate than T3 - especially for those who have never had any thyroid issues.

My point being that half-life is very much not a 'fall off a cliff' issue.

And, while radioactivity half-lives are extremely precise and well-defined, the same simply isn't true for our complex biochemical systems! They are usually strictly related to blood levels (ignoring cell content, lymph, cerebrospinal fluid, etc.).

And they are often derived from healthy subjects.

And some have been studied using radioactive tracers which is interesting. But again doesn't really work the same in those with high or low levels of the substance being studied.

[arTistapple]

I have had to think about your reply. It now makes sense. I hope! The great importance being (for my own thinking processes) is that once T3 enters the cell, no matter what it’s up to, that particular T3 can no longer be measured by ‘normal’ and available testing. It’s there working/or perhaps not. BUT we may still see or feel the benefits.

This off course is where we want it to be working. So even our T4 and T3 blood tests are only a partial guide.

No wonder TSH is so inaccurate and of such limited use. It’s not even in the next room, never mind the next street.

[helvella in reply to arTistapple]

Yes!

Imagine a single T3 molecule ends up helping to repair a single cell of our bones.

Lots of bone has a turnover in excess of ten years. Thus the half-life of the effect of that T3 molecule is incredibly long.

(Of course, another T3 molecule might be used in a process which is extremely brief.)

[arTistapple in reply to helvella]

Yes! Fantastic!