Useful article by Tania Smith (Canadian Thyroid Patients forum) on how reverse T3 acts to counteract T3 in cells (not by receptor blockage)

[diogenes]

Deiodinase Type 3 plays the T3-blocking role

thyroidpatients.ca/2019/11/...

[edited by admin to include link]

[Nanaedake]

Useful excerpt

'Individuals vary so much in thyroid hormone metabolism, especially in thyroid disease and thyroid therapy, that you cannot assume adequate FT3 from looking only at FT4 or TSH levels.

One ought always to consider baseline FT3 levels in context of concurrent FT4 availability, and see how the body responds if dosing and levels change over time.'

[LindaC]

Most interesting! Thank you.

[humanbean]

That article went so far over my head that it was practically in outer space. *Sigh*

[DippyDame]

Tania Smith writes some excellent stuff....but this strikes me as a lot of useful info that has drifted into fog.

[diogenes Remembering]

The summary of the concept is that T3 and reverse T3 do not compete for binding sites which promote or inhibit cell activity. What actually happens is that in different circumstances either the Deiodinase (DIO2) that converts T4 to T3 is having the greatest effect, or in other circumstances the Deiodinase DIO3) that converts T4 into rT3 dominates. These deiodinases determine what will enter the cell. By patrolling outside, they either promote T3 production and entry into the cell at the expense of rT3, or vice versa, when the rT3 producing Deiodinase is stronger. It's a matter of simple competition. Healthy conditions will make T4-T3 the chief product, whereas in ill health the T4-rT3 setup predominates. This latter will also occur if too much T4 is given in T4 therapy. In this case the DIO3 becomes important in diverting hormne conversion away from T3 (which would be too much) into rT3 instead.

[diogenes Remembering in reply to diogenes]

She has a new blog that explains more closely:

Deiodinase Type 3 plays the T3-blocking role

[DippyDame in reply to diogenes]

Thank you....the earlier fog has cleared a little!

[Nanny23]

Diodinase D3. What is that exactly please?

[Hidden in reply to Nanny23]

D3 is one of the deiodinase enzymes that remove Iodine from thyroid hormone molecules.

For example, T4 has 4 iodine atoms and T3 has 3, hence their names.

Different diodinase enzymes take one iodine atom from T4 (for example) and change it into either T3 or RT3 (reverse T3).

Reverse T3 is slightly different (a different shape I think) from T3 and can't do T3's job of helping produce energy. It's a bit like having two very similar keys but only one will fit into a particular lock). It doesn't stick in the lock though, as some say, and doesn't stop T3 getting in. It just means the balance of different deiodinases may hinder enough T3 being produced.

If there's not enough T3 there's not enough energy for the cells to work properly. If there's too much T3 the cells go into overdrive, which is also harmful. If you have are healthy, too much T4 is neutralised by changing it into Reverse T3.

Is that correct, diogenes ?

The whole thing is extremely complicated, so don't worry if you find it difficult. I do too, even though biology is my main interest and qualification.

Hope that helps, Nanny23, humanbean

[greygoose in reply to Hidden]

If you have are healthy, too much T3 is neutralised by changing it into Reverse T3.

No, I don't think that's right. To do that you would have to put one iodine atom back on and take another one off. I really don't think that happens. But, perhaps you meant to say 'too much T4'.

[Hidden in reply to greygoose]

that's a thought. Need to read up on it more. Can't get things into my head as easily as I used to. Getting old or hypo brain, not sure! Good excuse anyway!

[Hidden in reply to greygoose]

perhaps you meant to say 'too much T4'.

Yes, I did. Corrected now x

[helvella Administrator in reply to Hidden]

Reverse T3 is slightly different (a different shape I think) from T3

There are four iodine atoms in T4. If one particular iodine atom is removed, you get T3. If a different iodine atom is removed, you get rT3.

Have a look at the diagram linked below. The letters "I" represent iodine atoms.

en.wikipedia.org/wiki/Rever...

That is, it is which iodine atom was removed rather than shape, as such.

[Hidden in reply to helvella]

"If a different iodine atom is removed, you get rT3"

Of course, that does ring a bell! And because it's a different iodine removed, I imagine that would change the configuration/shape

[helvella Administrator in reply to Hidden]

I have just found a molecular diagram site which has bigger images which you can move around!

Not sure what computers/browsers it will work on – I am using Firefox on Windows 10.

T4 Levothyroxine

molview.org/?cid=5819

T3 (Triiodothyronine)

molview.org/?cid=5920

Reverse T3

molview.org/?cid=644280

[Hidden in reply to helvella]

Had fun twirling them around! Complicated shapes in 3D

[Hidden in reply to helvella]

Like if you had two apples in one hand, one in the other and one balanced on your raised foot.

If one apple was removed, the way you lean to keep your balance would differ depending on which apple was removed!

[helvella Administrator in reply to Hidden]

That is true, but just saying "shape" could confuse with the way stereoisomers differ. For example, we all refer to levothyroxine but there is also dextrothyroxine which has exactly the same structure but twosted in a different direction.

[Hidden in reply to helvella]

Oooh, never heard of dextrothyroxine! Does it occur naturally? I tried to look it up but couldn't see it, except as a failed medication

[helvella Administrator in reply to Hidden]

That is why you don't hear of or see it! It failed.

But it is because of its existence that the name "thyroxine" was refined to "levothyroxine" a number of years ago. Science had long known about the two forms but it did not seem necessary to write it out on the packets for patients. The change was to consistently use the same name in science, medicine, pharmacy and for patients.

[Hidden in reply to helvella]

Oh of course, Dextro and Levo stereoisomers! DUH! Levo is "Left handed" like me, so of course that's the best one

[Luna1390]

Maybe one of you can help me with my question: my RT3 was 9 while I was on NDT only. I added 25 mcg of Synthroid (I wasn't able to tolerate more NDT). I feel really good now. But... my RT3 went up to 19. Does this mean anything at all? My other labs are not too high. FT3 and FT4 are mid-range.

[jimh111]

If you are interested in this topic I would urge you to study the orignal source material which alas is complex and hard to learn. Unfortunately, although well intentioned Tania's two articles on D3 have at least half a dozen fundamental errors along with confusing text. The problem with many similar articles is that patients new to the subject might assume they are accurate and subsequently have to 'unlearn' what they have read. More care should be taken before they are published. This applies equally to the formal medical journals who are equally capable of publishing poor quality studies (and obstructing the good ones).

Two good sources of information on deiodinase are Thyroid Disease Manager thyroidmanager.org/chapter/... (register for free access) and Bianco Lab deiodinase.org/ . Deiodinase is a complex subject that takes some studying but I believe it is vitally important to the diagnosis and treatment of thyroid disorders.

[DippyDame in reply to jimh111]

I thought it was just me!