New paper access

[diogenes]

Re my earlier info on this site, the journal has stated that the article/paper will be available within 24 hours at the site dx.doi.org/10.1530/EC-15-0056. I don't know whether the site is personal to me, but the journal says it will be available also on PubMed. Hope you can access it to read in due course.

[Clutter]

Thanks, Diogenes. Just tried and it isn't active yet. I'll try again in 24 hours

[kaliayev]

Still not active. Really waiting for it!

[PR4NOW]

Thanks Diogenes, it is now available as of about 6 AM, Wednesday, UK time. PR

[kaliayev]

Thanks again, diogenes. It's strangely refreshing to read a sane paper on thyroid, talking on FT3 levels, deiodinase activity and... T4-T3 conversion (heresy!).

Could you explain a bit how you calculate the "sum activity of peripheral deiodinases"? I didn't know there was a way to calculate the deiodinase activity, beyond the T3/T4 ratio.

By the way, I really loved this part: "We speculate that L-T4 induced conversion inefficiency could prevent some vulnerable subjects from reaching true tissue normality on T4 mono-therapy alone. Those were not analysed separately in the numerous earlier T3/T4 trials and could be possible candidates for a combined T3/T4 treatment option, as recognized by some authors and the guidelines of the European Thyroid Association (46,47). " I never understood why we, as patients, don't talk more about the ETA guidelines on combination therapy. When I read them I thought they were a pretty good first step.

Thanks again!

[diogenes Remembering in reply to kaliayev]

Calculation of the sum activity of deiodinases can be done two ways - easy and harder. The harder way unfortunately is most likely to be more correct. The easy way is measuring the FT3/FT4 ratio - this assumes that the converting deiodinases are not saturated with substrate (i.e. T4) and so you get a direct relation then between T4 supply and T3 production. However, it is more likely that the enzymes are nearly saturated with T4 substrate in which case that horribly complicated equation in the text more closely shows the right result. This is because now T3 production is not linearly related to T4 supply.

[mickstability]

Thanks Diogenes - the paper seems to confirm in passing what some of us post - cancer subjects have found; T4 monotherapy doesn't make as much fT3 available for a given dose as it does in other patient groups, hence the difficulty we have in achieving a euthyroid state compared to others.

This study, ncbi.nlm.nih.gov/pubmed/218... from 2011 with which I'm sure you're familiar, also adresses the subject.

Again thanks.

[kaliayev in reply to mickstability]

Completely agree with you. I think this situation is similar for all patients that have had a thyroidectomy (for cancer or other reasons). I got a TT myself for Graves and my FT3 didn't get into range until a nice endo prescribed T3...

Now it would be interesting to try to correlate higher T4/T3 after thyroidectomy with worse clinical outcome and better response to combination treatment. The idea is kind of obvious; it makes you wonder why it has not been studied before.

[diogenes Remembering in reply to kaliayev]

Actually our group is working on devising a properly controlled clinical trial which will include that concept. So far we've done a pretrial simply to see what we could find out in the trial proper. There's no doubt that QoL (quality of life) as defined by accepted phenomena is directly related to FT3 (the lower the FT3 the worse the QoL on average). Also we now know that we have to account for body mass and age because these have an effect on the results and unless catered for, can obscure the real answers.