Dr. Tania S. Smith(PhD) on the Ratios of T4/T3

[PR4NOW]

Another thoughtful post by Dr. Smith. Link follows. PR

thyroidpatients.ca/2019/05/...

[helvella Administrator Thyroid UK]

Good to see diogenes and his colleagues referenced three times on that post.

[jimh111]

I’ve only skimmed this document as I’m a bit tired and I don’t think it is of much relevance! We can get hung up on ratios and sink deep into the technicalities. It seems to me much simpler to deliver sufficient T3 from liothyronine or NDT such that the patient gets typical fT3 and fT4 levels (ideally with slow release T3). Often when we do this we find that it doesn’t help many patients who are not doing well on levothyroxine. Clearly the problem is something else. We are in danger of studying something in detail that doesn’t do much to advance patient care.

Ironically, I believe the much maligned peripheral conversion is the root of many of our problems. I’m doing a write up on this which should be available in a couple of weeks.

[helvella Administrator Thyroid UK in reply to jimh111]

(ideally with slow release T3).

Is there a slow release technology that truly manages even release? If they are imperfect, how much better are they than other approaches such as split-dosing?

I ended up thinking that a micro-dosing device straight into the bloodstream might be the best approach. But I am not aware that it has ever been tried - even as short-term research.

The importance of the document, as I see it, is that it continues to point out that concepts around ratios might as well be binned, especially when they end up under-dosing because the concept is given prominence while FT3 is dismissed.

[diogenes Remembering in reply to jimh111]

Tania Smith was commenting adversely on the fractional production of T4 and T3 direct from the thyroid, which is of no value in determining conversion adequacy. Indeed the fractional production can vary wildly as the thyroid's activity changes. In a dying tyroid, the relative T3 production can easily exceed the T4 production. This makes up for the lower amount of T4 produced that the body can convert. However, but only on T4 mono therapy and in a patient with no thyroid, the T4/T3 ratio is indicating roughly the conversion efficiency by the body. If this gives a FT3 low in range, FT4 high in range, with a ratio greater than 4.5/1 (disregard TSH) then such a patient will require T3. Simply giving more and more T4 raises both FT4 and rT3, but not FT3. A futile exercise.

[LAHs in reply to diogenes]

You took (most of) the words out of my mouth. I didn't recognize the 13:1 and 16:1 ratios top of page 1. I had to look up the ratios that I had calculated from my own measurements before I realized that the article is talking about total T3 and total T4 and not FreeT3 and FreeT4, I think she should have said that early on in the paper. No wonder it's difficult to pin down a typical (or perfect) ratio, I think we all agree these slosh around a lot diurnally.

She does not mention at all the most important ratio of all, FT4 to FT3 i.e. how efficiently do you "make" FT3, the stuff which will make you feel well. A most important factor when it comes to thyroid hormone therapy is that the source of NDT is that we can only get it in the animal ratio, 3:1 and not 4:1, the human ratio. Btw, I like to read those ratios as "How many FT4 molecules does it take to make one FT3 molecule". [An aside: I take pig NDT (3:1) and Forest puts Levo in it presumably to upgrade the ratio to the human 4:1 (i.e. 38 T4 to 9 T3) but my (Free) ratio always comes out as 3:1 - the pig ratio.]

But, on the positive side it is a good extensive analysis of many things you might have wondered about.

[kissemiss in reply to jimh111]

I do not think that slow release T3 works because too many rely on many supplements which will interfere with t3 (where often a 4 hour gap is needed). Just a reflection.

[jimh111 in reply to kissemiss]

I was thinking of a hypothetical perfect slow release T3 tablet. Even if we had one I don't think it would help the patients who do very badly on levothyroxine only. I suspect these patients have problems that require abnormal T3 / T4 proportions. Such a tablet would be great for many patients who are reasonably well on levothyroxine only therapy.

[diogenes Remembering in reply to jimh111]

In a sense NDT can be regarded as a form of slow release. A good deal of the T4 and T3 in NDT will be bound onto thyroglobulin, because that is how they are made and the free T4 and T3 is released from it on entering the bloodstream naturally from the gland. If taken by mouth, then the stomach enzymes have to break down the NDT thyroglobulin and release the T3 and T4. This must take some time. Accordingly it would be of huge value to compare the pharmacodynamics of T4 and T3 uptake using NDT on the one hand and T4/T3 combination on the other. The trouble is that there's no incentive to do this comparison because of the closed mindedness that NDT is no good and uncontrolled in content, which it of course is not. In any event the most finely controlled pill has to confront the different uptakes caused by food interference for example, so that the efficiency of any pill however well controlled is severely affected by the individual's ability to take it up.

[jimh111 in reply to diogenes]

Interesting. I would love to see a careful trial of NDT v. (L-T3 + L-T4) in doses that deliver similar fT3, fT4 levels. It does seem that some patients respond to NDT and not combined L-T3, L-T4 therapy. I would like to know if this is really true and if so, why. A very obvious optimal approach would be to prescibe levothyroxine plus NDT, delivering a bit of everything in an appropriate ratio.

[PR4NOW in reply to jimh111]

jimh111, I have a relative (TT) who had started on NDT (3 3/4 Gr.) and did just fine until the UK switched to L-T4 in 1978. They spent 2 1/2 years with an endo trying L-T4 and L-T3 in all combinations and alone and it didn't solve the problem. He switched them back to NDT and they recovered their health. We often joked that there must be a mysterious factor X in NDT that has yet to be discovered. They also noticed that if they could get really fresh product it produced a stronger effect than product that had been in the usual supply chain. They were getting it from the production plant for awhile. I agree with Diogenes, studies on pharmacodynamics are needed and I would like to see a more thorough analysis with the tools available now of just what is in NDT. PR

[jimh111 in reply to PR4NOW]

This is the general impression I get. It's possible there are undiscovered hormones or substances in NDT. We really need good NDT v. synthetic trials and if there is a difference follow-ups on what amount of NDT is needed to resolve symptoms. Is the benefit of NDT due to thyroid hormones, or another substance? Also, why do so many people do well on synthetic only? A lot of research that should have been done over the past 50 years.

[PR4NOW in reply to jimh111]

jimh111, couldn't agree more with what you said. At the moment I'd settle for endocrinology recognizing that people are unique and accepting NDT and T3 as legitimate treatments. And stop all the shortages of thyroid medication. PR

[PR4NOW in reply to jimh111]

jimh111, also Dr. Blanchard was using 98.5% L-T4 + or - with 1.5% compounded slow release NDT with good results although he did a lot of seasonal adjustment. PR

[jimh111 in reply to PR4NOW]

Interesting. Would suggest another substance behaving a bit like a vitamin.

[Aurealis in reply to diogenes]

The T3 in NDT feels like slow release to me, as compared to T3 in Liothyronine. I take both.

[SilverAvocado]

Great article Like jimh111, my blood pressure slightly raises when I see the phrase 'ratios of T4/T3' because we read so much awful stuff about it. Good to see it debunked, and I particularly enjoy some of the social science touches, like drawing attention to 'the' human body we often hear about

[Annkapp]

Thanks so much for sharing that post!

[dtate2016]

Thanks so much for posting this extensive Research. Really like the part that talks about enzymes and the conversion process.

[Aurealis]

I do wish this was compulsory reading for all GPs. It could go on their shelves next to the ‘Take a tablet a day and you’ll be fine Manual’