Failing thyroid gland!

[DippyDame]

I'm sure this has been previously posted but....

paulrobinsonthyroid.com/new...

It's important!

[tattybogle]

The statement that paul makes in his interpretation of the paper by diogenes et al

"this is not controlled by TSH either"

needs to be better explained and justified.

because no such statement is found anywhere in the original paper from diogenes et al , quite the opposite in fact ,, the paper frequently poses that TSH is the driver for the increase we see in thyroidal T3 production in the failing thyroid gland .

in context paul writes:

"The article is saying that in a declining T3 environment (not a euthyroid healthy state) the central role of the thyroid gland is paramount in maintaining healthy T3 levels. This is through the gland’s ability to shift as much of its ability as possible into making T3. This is not controlled by TSH either. It is as another of the author’s says, “Strong T3-protective mechanisms of the control system emerge with declining thyroid function when glandular T3 secretion becomes increasingly influential over conversion efficiency.”

They also conclude that this shows once again that the influence of TSH is being overestimated and the reliance on it to determine whether someone is properly treated, or not, is flawed."

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

But ...... compare this to multiple quotes from the original paper, all clearly suggesting the feedforward role of higher TSH is responsible for causing the observed increase in de novo T3 production in the failing thyroid :

"Results: During the modelled transition to hypothyroidism, central control imposed an increasing influence in maintaining serum FT3 levels, compared to peripheral conversion efficiency. Numerical continuation analysis revealed dependencies of T3 production on different elements of TSH feedforward control"

"Hence, we sought to further explore the influence of TSH stimulation on both thyroidal T3 secretion and T4-T3 conversion, hypothesising that it would become increasingly apparent under conditions of thyroid stress"

"Our modelling strategy aimed to extend the well-known mechanisms of hypothalamic-pituitary-thyroid feedback control by thyroid hormones with additional elements of central feedforward control on T3 generation"

"TSH feedforward control has only recently been formally introduced to thyroid modelling..... Here, we used five nonlinear ODEs of first order to model the feedback regulation of pituitary TSH and hypothalamic TRH by thyroid hormones together with the feedforward control of intra-thyroidal T3 production by the pituitary hormone. This adds a central path to thyroidal T3 production."

"Within the thyroid, T3 generation originates from two distinct pathways, either de novo synthesis from proteolysis of thyroglobulin or conversion from T4 via monodeiodination with two enzymes, deiodinase 1 and deiodinase 2, both of which are activated by TSH"

"We included the TSH dependency of the T3-generating processes within the thyroid. Predicted FT3 outcomes at equilibrium were plotted against TSH concentrations (Figure 1)".

"In a sensitivity analysis, specific structural parameters were varied affecting the relative contributions of glandular conversion efficiency and direct T3 secretion under the conditions of a declining thyroid reserve. This demonstrated both the overall efficiency and the conditional adaptation of the multiple participating elements in the TSH-dependent feedforward control (Figure 3)"

"The latter combines the classical negative FT4-TSH feedback loop with TSH-dependent positive control elements on thyroidal T3 secretion and enzymatic T4-T3 conversion"

"Apparently, the human thyroid relies more on increasing its own efficiency rather than requiring other organs to remedy the situation. A protective role of this pathway is further supported by experiments in genetically manipulated animals able to maintain thyroid health despite being deficient in all deiodinating enzymes.37 The biochemical mechanisms involve TSH-stimulated iodination of the thyroglobulin molecule, thereby favouring T3 production over T4"

[DippyDame in reply to tattybogle]

Burning the midnight oil tatty??

We are preparing for a family "invasion" so will need to read this when peace and quiet return!

Since you question Paul's comment, and I can see why, perhaps you should contact him and ask if he will be good enough to explain and justify that statement.

My dinosaur brain has clearly lost it's edge so I'm happy to leave analysis of the biochemistry to those retaining sharper perception and who have very much greater knowledge.

Here I quote diogenes readily understood explanation of feedforward, from another post...

It's when, if the thyroid is failing and T4 supply is waning, then TSH rises. In doing so it stimulates what's left of the thyroid to keep on producing T3 as near as possible to that in health. That is feedforward - TSH stimulation but only to maintain T3 production even if T4 production is going down.

Hope the now white shirt passed inspection!!