Showing the pharmacological relationship of T4 and T3

[diogenes]

There has been some degree of controversy over how much T4 is equivalent to T3 and vice versa in pharmcological terms of the potential activity of either hormone. The paper below discusses this in some detail - working with thyroidectomised patients so as not to get thyroidal interference. The answer comes out as 3 units of T4 are equivalent to 1 unit of T3 - ie weight for weight T3 is 3x more active pharmacologically than T4

The pharmacodynamic equivalence of levothyroxine and liothyronine. A randomized, double blind, cross-over study in thyroidectomized patients

Francesco S. Celi, Marina Zemskova, Joyce D. Linderman, Nabeel I. Babar, Monica C. Skarulis, Gyorgy Csako, Robert Wesley, Rene Costello, Scott R. Penzak, and Frank Pucino

Clin Endocrinol (Oxf). 2010 May; 72(5): 709–715.

doi: 10.1111/j.1365-2265.2009.03700.x

[helvella Administrator Thyroid UK]

Thanks diogenes.

onlinelibrary.wiley.com/doi...

[jgelliss]

Thank you so much for this Great and Valuable information Diogenes . I always wondered about exactly this formula. Having had TT myself . And not having much knowledge about T4 and T3 doses. And not getting much information from Dr's unfortunately for us the patients. It's very possible that Dr's themselves know very little about this too.Very Grateful and very Thankful for all the knowledge and information that you share with us.

[LindaC in reply to jgelliss]

Hear Hear! We need this level of information.

[LindaC]

Thank you diogenes - for eveything you provide us with - so appreciated.

[jimh111]

About half of the trials comparing L-T3 / L-T4 combination therapy with L-T4 monotherapy subsituted L-T3 for L-T4 in a 1:4 or a 1:5 ratio. These studies tended to be the ones that found no benefit for combination therapy. Francesco Celi's study invalidates these trials, a point that is never mentioned in the meta-analyses.

About three years later Celi did a follow-up study pubmed.ncbi.nlm.nih.gov/235... which demonstrates that the pharmacodynamics of combination therapy is comparable to monotherapy in terms of the effects on TSH between doses. i.e. L-T3 / L-T4 therapy has the same effect on TSH as L-T4 monotherapy, there are no spikes of activity, you can't see a difference. The claims that T3 therapy leads to erratic hormone activity seem unfounded, at least in the pituitary when patients are taking three divided doses daily.

[helvella Administrator Thyroid UK in reply to jimh111]

And he was a named author on this paper earlier this year!

Eur Thyroid J

. 2021 Mar;10(1):10-38.

doi: 10.1159/000512970. Epub 2021 Feb 16.

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

Jacqueline Jonklaas 1 , Antonio C Bianco 2 , Anne R Cappola 3 , Francesco S Celi 4 , Eric Fliers 5 , Heike Heuer 6 , Elizabeth A McAninch 7 , Lars C Moeller 6 , Birte Nygaard 8 , Anna M Sawka 9 , Torquil Watt 10 , Colin M Dayan 11

Affiliations

PMID: 33777817 PMCID: PMC7983670 (available on 2021-09-01) DOI: 10.1159/000512970

pubmed.ncbi.nlm.nih.gov/337...

[jimh111 in reply to helvella]

Yes, if I remember correctly it suggests ways forward for future combination therapy trials. It seemed better than average although my view is that they fail to grasp the basic science. When patients have poor conversion, as evidenced in TFT results it is not sufficient to normalise serum hormone levels, this still leaves low tissue T3. Thus, all the studies are predicated on a false assumption.

Torquil Watt gave a talk to The Thyroid Trust in London a little over a year ago. He developed THYPRO a tool for assessing thyroid symptoms during trials. It seems pretty good, I find it a dull subject but these tools are essential for effective research studies.

[JGBH]

Thank you so much. I had read what the ratio is somewhere else but can’t remember. This confirms it.