Central hypothyroidism and T4-T3 conversion

[diogenes]

Here is a summary of a paper describing effects of pituitary failure on thyroid parameters:

L-T4 MONOTHERAPY IS NOT ADEQUATE FOR NORMALIZING SERUM FT3 IN MOST PATIENTS WITH CENTRAL HYPOTHYROIDISM

D. Gullo1, A. Latina1, I. Marturano1, A. Caff1, P. Tita1, G. Parrinello1, S. Squatrito1, R. Vigneri1

1Endocrinology, Department of Clinical and Molecular Biomedicine, Garibaldi-Nesima Hospital - Catania

Context. In central hypothyroidism (CH) the treatment of choice, as in primary hypothyroidism, is L-T4 because peripheral conversion to T3 is believed to account for the overall tissue requirement for thyroid hormones. In these patients TSH cannot be used to evaluate euthyroidism and FT4 is currently the most used measurement to adjust the replacement dose. In a large series of CH patients we evaluated whether L-T4 monotherapy can normalize serum thyroid hormones, and more specifically, the most active hormone FT3. Methods. In a cross-sectional retrospective study we measured FT3, FT4 and FT3/FT4 ratio in 76 CH patients, median age 58 yrs (IQR 37-69), M=33 F=43, all having normal FT4 serum levels under L-T4 monotherapy (reference range 9.0-20.6 pmol/L). Data were compared to those observed in a cohort of euthyroid controls (n=3,875). Results. In L-T4-treated CH patients median FT4 levels (14.0 pmol/L) was not different from those of euthyroid controls (13.2 pmol/L; P=0.60) whereas median FT3 was significantly lower (3.11 pmol/L vs 4.47; P< 0.001). In L-T4-treated CH patients, 97.4% had FT3 levels below the median FT3 of controls and 35.5% had FT3 lower than the reference range (2.93-6.01 pmol/L). The FT3/FT4 ratio, an index of peripheral deiodination, was 0.23 vs 0.32 (P< 0.001). FT3 and FT4 levels were influenced by gender, age and the treatment with other pituitary hormones. In 26 CH patients having serum FT4 in the highest tertile, suggested as the target value for optimal L-T4 therapy, FT3 levels were below the median FT3 of reference range in all cases and below 2.5 percentile of the normal range in 8/26 cases (30.8%). Conclusions. CH patients on L-T4 monotherapy have FT3 levels significantly lower than euthyroid controls, despite normalization of FT4. Most important, in one third of cases, even when FT4 is in the higher range, FT3 is often lower than the reference range, indicating that these patients’ ability to convert T4 to T3 is insufficient. The accompanying pituitary and peripheral hormone deficiencies may play a role in the reduced FT4 to FT3 conversion. These data indicate that FT4 alone is not sufficient for assessing TH status in CH patients. L-T4 monotherapy may not adequately guarantee euthyroidism in a significant subgroup of CH patients that may require a more physiological treatment with combined L-T4 and L-T3 administration.

[BadHare]

Thanks again, diogenes !

I've never taken T4 only, so can't compare. An article to wave at my GP, perhaps!

[SilverAvocado]

Wow, what an extremely useful and clear set of results!

Very sad to read of those that have a high freeT4 but still below range freeT3. They must be having a terrible time of it.

[Musicmonkey]

Fab!! Is there a link to the paper please?

[diogenes Remembering in reply to Musicmonkey]

This is a "poster" presentation in Journal of Endocrinological Investigation, volume 36, supplement to part 5, Abstract no 57, 2013. A site to download is:

iris.unipa.it/bitstream/104...

[linda96]

I have pituitary issues so this is v welcome for me - I will download and take to my next hypopituitarism Consultant meeting.

[dolphin5]

Diogenes, would it be fair to say that if we have had our thyroid gland removed, and we need above range FT4 even to get low or below range FT3, that the resulting suppressed TSH puts us in the same position as someone with central hypothyroidism? (I don't want my endo to say "but this research doesn't have any bearing on your case".)

[diogenes Remembering in reply to dolphin5]

Practically, yes but not for the same reason. Thyroid removed - the pituitary still responds to T4/T3 and will be suppressed. Pituitary faulty - you can still suppress with excess hormone, but you can't always convert enough T4 into T3 in the body. Stimulation of deiodinase isn't practical since there's not enough TSH to do it.

[dolphin5 in reply to diogenes]

Thank you.

[Tansin22 in reply to diogenes]

So how would starting dose of LT4+LT3 look like ? How will one know that he/she is on correct dose ?

[Angel_of_the_North]

Empirically true for me - not there's a study, too.

[Gcart]

Sorry but I am thick, with no thyroid! Does that mean that because my TSH is suppressed that that hormone , TSH, isn’t enough to stimulate the T3 to be conveted adequately? No matter what 🤔

[diogenes Remembering in reply to Gcart]

You've no thyroid therefore on high dose of whatever, TSH is suppressed. T4-T3 conversion is then governed by how much T4 you take. Too much - it inhibits T4-T3 conversion and rT3 is produced as a drain. Its now mechanical - control your T4 uptake if on monotherapy so as to achieve a good FT3 if you can. If you can't then add T3.

[Gcart]

Thank you diogenes , I have added T3 with good effect. It all adds up to a better understanding as to why .

[lady_eve]

Having just been told that my hypothyroidism is central in origin (after 'only' thirteen years) I am trying to learn all I can about it. This piece is very welcome, thanks.