Parts 3 and 4 of Tania Smith's Canadian Thyroid Advocacy is now available

[diogenes]

Tania Smith concludes her analysis of thyroid function and treatment

[SlowDragon Administrator]

Links to all four parts

Part 1

thyroidpatients.ca/2019/12/...

Part 2

thyroidpatients.ca/2019/12/...

Part 3

thyroidpatients.ca/2019/12/...

Part 4

thyroidpatients.ca/2019/12/...

[jimh111]

Thanks for this and your work on the original study, this article does make it a bit easier to read it.

There is one important error in the article where it says: -

The thyroid hormone economy progressively increases the body’s global deiodinase activity, upregulating deiodinase type 1 and type 2 in order to increase peripheral conversion of T4 to T3 as it experiences a decline in production of T4 and T3 hormone from the thyroid gland.

(This statement is not in the orginal paper).

It is generally accepted that D1 is downregulated as T3 and T4 decline whereas D2 is upregulated. This is important, D2 is primarily expressed in tissues such as the brain and skeletal muscle. D2 converts T4 to T3 in the endoplasmic reticulum which is close to the cell nucleus and this T3 remains close to the receptors for several hours and so is more likely to activate gene expression. The cruical point is T3 derived from D2 has a different role to circulating T3, it is able to enhance local T3 action.

I believe an overlooked corollary is that if we replace this D2 derived T3 by supplying enough T3 to restore serum fT3 (or total T3) it will not restore euthyroidism in those tissues reliant on the local action of D2 derived T3. These organs (brain, skeletal muscle) will require higher circulating T3 levels to overcome the loss of locally generated T3.

So a reduction of TSH has two consequences: (1) a reduction in circulating T3 as described in the original study and (2) a loss of local D2 derived T3.

This problem is made much worse when there is subnormal TSH secretion as can happen in a down-regulated axis. In this scenario the much lower TSH futher reduces local T3 in tissues expressing D2. Even worse, when there is insufficient TRH stimulation the pituitary produces TSH isomers with substantially reduced bioactivity. In these cases the activity level of the TSH is considerably less than the assay results suggest. We see examples of this when patients with marginal fT3, fT4 results present with life wrecking hypothyroidism.