Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease

[helvella]

This paper is about an extremely rare form of hypothyroidism. The text is quite dense and not an easy read.

Most of us have no reason to go further.

However, for those who are interested in thyroid beyond their own issues, it is really quite interesting.

If you give up after a sentence - don't worry.

REVIEW article

Front. Endocrinol., 04 September 2013 | doi.org/10.3389/fendo.2013....

Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease

Cristina Luongo, Luigi Trivisano, Fausta Alfano and Domenico Salvatore*

• Department of Clinical Medicine and Surgery, University of Naples “Federico II,”, Naples, Italy

The major product secreted by the thyroid is thyroxine (T4), whereas most of the biologically active triiodothyronine (T3) derives from the peripheral conversion of T4 into T3. The deiodinase enzymes are involved in activation and inactivation of thyroid hormones (THs). Type 1 and type 2 deiodinase (D1 and D2) convert T4 into T3 whereas D3 degrades T4 and T3 into inactive metabolites and is thus the major physiological TH inactivator. The hypothalamic-pituitary-thyroid axis maintains circulating TH levels constant, while the deiodinases tissue-specifically regulate intracellular thyroid status by controlling TH action in a precise spatio-temporal fashion. Here we review the data related to the recent identification of a paraneoplastic syndrome called “consumptive hypothyroidism,” which exemplifies how deiodinases alter substantially the concentration of TH in blood. This syndrome results from the aberrant uncontrolled expression of D3 that can induce a severe form of hypothyroidism by inactivating T4 and T3 in defined tumor tissue. This rare TH insufficiency generally affects patients in the first years of life, and has distinct features in terms of diagnosis, treatment, and prognosis with respect to other forms of hypothyroidism.

Full paper freely accessible here:

frontiersin.org/articles/10...

[Charlie-Farley]

We are in the midst of winding down business and no time to read frustrating! I'm saving posts like 'billio'. Lots to read when we finally land again. thank you helvella 😀👍

[radd]

helvella,

I love reading about elevated RT3 😬 ... and this really is a very interesting read that aside from D3’s destructive role in Consumptive Hypothyroidism emphasises how important the considerings of degradation & clearance really are in general, as opposed to just increasing med doses when hypo's don't recover health.

I also love it every time I read about thyroid hormone receptors (TRβ2 in this instance) expressed primarily in the blah, blah, blah and …. inner ear. Many members (including myself) have experienced inner ear issues that not even an endo will associate to the workings of our thyroid hormone, even though we say our ear symptoms improve/reverse with optimised levels. I often think some scientists would be better placed to hold the prescription pad.

I have previously read about the elevated RT3 levels in fetal thyroid activity that acts as a barrier to the elevated T4 levels in maternal-fetal exchange. It’s as if some babies don’t progress on from what happens naturally in pregnancy. Poor baby who died but how great they were able to perform such comprehensive testing that might help others with these tumours in the future. And they used T3 … flippin' loads of it!

And even a reference to “D3 is frequently overexpressed in malignant cells” which could take us right back to the cancer- causing high T4 levels recently discussed on the forum.

Great read, thank you for posting.

[tattybogle in reply to radd]

Glad you posted this . i was going to read it but forgot ... next time it's raining, i shall

[helvella Administrator Thyroid UK in reply to tattybogle]

I'm sure that won't be very far into the future...

[radd in reply to helvella]

Errr .. like now, here ☔️😬

[tattybogle in reply to radd]

'tis warm and sunny here .... was just in garden scowling at oil stains on path that No1 Son has made while taking car to bits....

[radd in reply to tattybogle]

Curiosity should be applauded, even in the presence of oil stains 🤣

[Havoc83]

Please could you expand on the symptoms of the ear problems?

[helvella Administrator Thyroid UK in reply to Havoc83]

I'm sorry I know no more than what is in this paper.

It was posted more for the general interest than the specifics. In other words, there are thyroid/thyroid hormone issues which are beyond the understanding of pretty much the entire medical establishment. And this paper points out a tiny corner that will almost inevitably be missed, dismissed, etc.