Where does T4 to T3 conversion take place?

It´s often said that T4 to T3 conversion is normal in thyroid patients as most of it takes place outside the thyroid gland; I´ve read that the total daily output of T3 from the gland is ca 10 mcg - half of it produced directly by the gland and half of it coming from conversion taking place inside the gland itself. So the rest - depending on source, the total daily amount of T3 needed by the body is 30-50 mcg - comes from extra-thyroidal conversion, mostly in the liver, but also in the kidneys and gut.

But Paul Robinson writes in "The Thyroid Patient´s Manual" (p. 142): "If you have lost thyroid tissue through a thyroidectomy or through Hashimoto´s thyroiditis, you will also have lost a substantial amount of T4 to T3 production. The thyroid gland converts more T4 than any other tissue".

He suggests this argument is used to convince doctors to prescribe T3.

Any thoughts?

[diogenes Remembering]

In health, the thyroid contributes directly an average (note average) 20% of the T3 found in the body. But this number is, like everything else, just an average. The study in question showed individual contributions from about 10% to over 30%. When you lose your thyroid, then this contribution is lost. To get some sort of health back on say T4 therapy, you need more than the healthy thyroid originally made to force the body tissues to convert enough T4 to approach the original FT3 level. In some people, it can't be done with whatever T4 you give. These are the patients who need T3 as well as T4. This is the argument to present to doctors.

[jimh111]

It used to be thought that most deiodinase took place in the liver but this is not so. The liver and kidneys express type-1 deiodinase (D1) which converts T4 to T3 and rT3. D1 is upregulated when serum hormone levels are high, so it's not very relevant to hypothyroidism. This paper onlinelibrary.wiley.com/doi... gives a very good description of current knowledge of the subject (as of 2014). It also references some of the key studies in this area. Most T4 to T3 conversion is done by type-2 deiodinase (D2) which takes place in organs such as the brain and skeletal muscles.

We should also bear in mind two points: -

1. During hypothyroidism (when TSH is high) the thyroid increases T3 secretion considerably with proportionally more T3 than T4. If you do not have a healthy thyroid this safety net is lost.

2. TSH promotes deiodinase. If TSH is lower than usual (for given fT3, fT4) there is reduced deiodinase leading to lower serum fT3 levels and cruically lower tissue T3 levels as local conversion of T4 to T3 (D2) is lost. Leovthyroxine monotherapy requires higher fT4 levels to restore normal serum fT3 resulting in a lower TSH which leads to lower tissue T3 levels as local T4 to T3 conversion by D2 is lost. This point is always overlooked.

[Hidden in reply to jimh111]

This could possibly mean that NDT (which is mostly T4) contains too little T3 for some patients...?

[jimh111 in reply to Hidden]

NDT has much higher T3 content than is secreted from the thyoid.

[Hidden in reply to jimh111]

And yet, so many people do much better on it than on levo...!

[jimh111 in reply to Hidden]

Because some people need more T3 than normal levels to compensate for loss of intracellular T3 caused by subnormal T3. Others may have a form of resistance to thyroid hormone caused by endocrine disrupting chemicals and require high T3 levels to compensate. It's also possible NDT contains other hormones or substances that we are not aware of.

[helvella in reply to jimh111]

I'm sure many of us would dearly love to see a truly comprehensive and well-executed analysis of desiccated thyroid in order to find out what is in there.

(Obviously, we'd need to see a number of tablets, across the available makes, analysed in order to have some idea how much the composition varies.)

Keep wondering how much that would cost?

[jimh111 in reply to helvella]

We don't even have a good crossover trial of NDT v. L-T3 + L-T4 in equivalent doses. This would show whether there is any unknown advantage to NDT. The advocates of NDT should bear the most responsibility for this.