Asymmetrical Transport of Thyroxine Across Human Term Placenta

[jimh111]

This new study pure.eur.nl/en/publications... is behind a paywall. I have a copy, it’s not easy to follow but essentially says little T4 crosses the full term placenta from mother to baby but T4 rapidly crosses from baby to mother. The authors suggest this may be a mechanism to protect the baby from maternal thyrotoxicosis (but not Graves’ disease, see later).

Type-3 deiodinase (D3) converts T4 to rT3 and T3 to T2. When D3 was blocked foetal T4 increased. The paper points out that more maternal T4 may be passed to the foetus during earlier stages of pregnancy when placental D3 activity is lower. Many endocrinologists, and a few studies assert that T3 cannot cross the placenta because it is blocked by D3 but the same argument seems to apply to T4 although D3 prefers to act on T3.

I’m not sure these studies are very helpful because they look at free T3 or free T4 and occasionally T3 or T4 bound to specific cellular transporters. In real life T3 and T4 are bound to serum transport proteins with the free components binding to cellular transport proteins in order to cross the placenta. Do any of these in vitro studies reflect what is actually happening?

Studies take donated term placentas, usually full term, a few premature. The baby insists on keeping the placenta until birth!

A bigger and more obvious issue is that in the early stages of pregnancy, when the mother’s hormone levels are crucial, there is no placenta! The placenta starts to function at three to four months. This raises the question of to what extent thyroid hormone transfer from the mother is regulated by the deiodinases and developing placenta.

This pdf download ashfordstpeters.net/Guideli... gives a good description of thyroid hormones during the early stages of development. It also asserts that T3 does not cross the placenta without offering any evidence. It gives detailed advice on the management of babies born to mothers who have had Graves’ disease.

I feel many endocrinologists are unethically creating fear of damaged babies when a mother takes T3. We simply do not know what happens in the early stages of pregnancy, where the baby gets its T3 from. It is wrong to pretend that we understand it. We do know that for over a century hypothyroidism has been teated with NDT and there is no record of harm. It’s possible that NDT therapy will carry a small increased risk compared to levothyroxine monotheapy, or vice-versa. The studies have not been done.

My view is that the obvious default situation is to give T3 and T4 in doses that reflect the healthy population, with different ratios where there is clinical need. It’s interesting to note that a small percentage of endocrinologists who assert T3 cannot cross the placenta will have mothers or grandmothers who were on NDT during pregnancy.

[helvella Administrator]

Interesting.

I guess that an athyreotic foetus would result in little or no T4 being transported from foetus to mother. Could that be a useful observation?

Briefly read an abstract (or similar) the other day discussing conversion of T4 to T3 in the placenta saying that is is a significant process. I imagine that happening if a reasonable proportion, or all, that T3 actually goes to the foetus - but maybe the placenta itself requires quite a bit of T3?

[jimh111 in reply to helvella]

It gets very complex which I why I adopt the don't know attitude. The studies tend to look at term placentas whereas what really matters is how T3 and T4 get to the foetus in the first half of pregnancy. During the first two months there isn't much of a placenta.

[HealthStarDust in reply to jimh111]

Exactly! How indeed?!

[DippyDame]

I feel many endocrinologists are unethically creating fear of damaged babies when a mother takes T3.

I think this says more about the individuals than about the T3!

If they want to find trouble they'll make sure they find a way to find it!!

Sometimes we just do not know why.....yet some things still work despite us!

Maybe the answer to the ultimate question of life, the universe and everything really is 42!!

But your "default situation" makes more sense!

[HealthStarDust]

This is something I’ve wondered about too. With no placenta, how is the baby getting any thyroid hormone until it develops its own? I simply do not much about human physiology or biology to even hazard a guess.

[helvella Administrator in reply to HealthStarDust]

How about thyroid hormone in amniotic fluid?

Thyroid Hormones and Thyrotropin in Amniotic Fluid

Inder J. Chopra, M.D., and Barbara F. Crandall, M.D.

Abstract

Thyroid hormone and thyrotropin concentrations in amniotic fluid were studied by radioimmunoassays during pregnancy. The mean thyroxine concentration was 398 ng per 100 ml at 15 to 19 and 440 ng per 100 ml at 36 to 42 weeks. Although 3,3′,5-tri-iodothyronine was undetectable (<25 ng per 100 ml), 3,3′,5′-tri-iodothyronine levels were very high (range, 132 to 605 ng per 100 ml) at 15 to 30 weeks, but decreased substantially (range, 54 to 130 ng per 100 ml) thereafter. Thyrotropin was undetectable. The mean thyroxine and 3,3′,5-tri-iodothyronine levels in amniotic fluid were much lower and the mean 3,3′,5′-tri-iodothyronine much higher than the corresponding values in maternal serum at both 15 to 19 and 36 to 42 weeks of pregnancy. Measuring thyroid hormones in amniotic fluid, especially 3,3′,5′-tri-iodothyronine, may aid in the diagnosis of fetal thyroid dysfunction and in identification of pregnancies of less than 30 weeks' gestation. (N Engl J Med 293:740–743, 1975)

nejm.org/doi/full/10.1056/N...

Yes - it does read as if it was intended to confuse and then they hide the paper behind a firewall. And it is VERY old - 1975.

[jimh111 in reply to helvella]

Leave out the VERY old bit mate.

[helvella Administrator in reply to jimh111]

I remember 1975 like it was yesterday...

[Lalatoot in reply to helvella]

It was yesterday, wasn't it?

[TSH110 in reply to helvella]

Hot summer

[DippyDame in reply to helvella]

Me too!!

[Polo22 in reply to helvella]

was that the hot Ladybird year, love the ladybirds but there were millions of the buggers

[helvella Administrator in reply to Polo22]

No - that was 1976:

bbc.co.uk/news/magazine-356...

[HealthStarDust in reply to jimh111]

It’s not young either! Middle age?

[HealthStarDust in reply to helvella]

Thank you! That’s very useful!

[HealthStarDust in reply to helvella]

Me again.

3,3′,5′-tri-iodothyronine what is this in lay persons terms??!

[helvella Administrator in reply to HealthStarDust]

Reverse triiodothyronine = 3,3′,5′-triiodo-L-thyronine, reverse T3, or rT3.

Triiodothyronine = 3,3′,5-triiodo-L-thyronine, T3.

The difference is in the "prime" sign on the 5.

[HealthStarDust in reply to helvella]

Thank you!

[humanbean]

It does strike me as odd that the paper talks about thyroid hormone transfer from mother to baby across the placenta at full term when the baby, by that stage, should have their own fully-formed thyroid, pituitary and hypothalamus controlling their thyroid hormone levels and TSH.

...

Many endocrinologists, and a few studies assert that T3 cannot cross the placenta because it is blocked by D3 but the same argument seems to apply to T4 although D3 prefers to act on T3.

There have been some women on the forum who have taken either NDT or T3 and had perfectly healthy babies at the end of pregnancy.

This is a case report on two pregnancies in the same woman who was on T3 only, and her children were very healthy.

healthunlocked.com/thyroidu...

[jimh111]

The study is looking at the placenta and so it is full term, they are trying to understand what the placenta does to thyroid hormones and acknowledge that more T4 will cross earlier in the pregnancy.As you note there is the fundamental issue that there have been millions of successful pregnancies with NDT which has a high proportion of T3 as well as many pregnancies on T3 only. It seems that most endocrinologists would prefer to lie about T3 and pregnancy as a means of suppressing T3 treatment.

[HealthStarDust]

The fact is, no one blooming knows with any certainty what’s going on thyroid wise in early pregnancy, or even too much later in the pregnancy. All the modern literature at least agrees on is a greater need of T4 during pregnancy, yet no plausible explanation on how that’s used or converted in baby. It’s a total misogynist blind spot in medical research!Or, have I missed something?

I remember trying to research this area at length at the start of my thyroid journey in all my fatigue and other symptoms and getting very angry and distressed at the lack of clear answers.

[DippyDame in reply to HealthStarDust]

All the modern literature at least agrees on is a greater need of T4 during pregnancy

Is it the T4 that is required ....or more accurately the T3 that is converted from the T4.

It's T3 that is the active hormone ...

Are they assuming that conversion is always adequate, so providing enough T3.

I don't see T3 as the villain....medics don't really understand it so make it sound complicated - dangerous even.

That is dangerous!

We can survive without T4 ....but not without T3

Just throwing in my tuppence worth!

[HealthStarDust in reply to DippyDame]

I assume that is what they have assumed. But, who knows?!

[jimh111 in reply to HealthStarDust]

Exactly. It does seem T4 is sufficient but experience seems to suggest T3 is also. It may be that the DIO2 polymorphism means that mothers need combination therapy for optimal outcome. We simply don't know and a trial would need large scale genetic profiling, perhaps tens of thousands.

[HealthStarDust in reply to jimh111]

I can’t disagree but I also can not see scenario where such a trial would ever be sanctioned. Well, not in the western world anyway.

[jimh111 in reply to HealthStarDust]

Initially they could simply look at babies born to mothers on levothyroxine by DIO2 polymorphism but it would need a large study.

[Polo22]

Really interesting will come back to this in a bit. Lots of comments/thoughts but haven't fully engaged brain yet, need more tea/coffee or methylphenidate 🤔