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Enzymes—deiodinase,selenium and iodine determine the T3-T4 ratio?

I just read an article talking about T3-T4 ratio, and RT3, written by Albert G. Burger, University of Geneva." Thyroid function tests", sorry that article was copied from a book, which could not be found on the internet.

Monodeiodination plays a crucial role in the control
of serum T3 levels. Three enzymes—deiodinase
types I, II, and III—have been characterized. They are
selenoroteins and, hence, very rare mammalian proteins.
However, they differ markedly concerning their
functional characteristics. Quantitatively, the most important
enzyme is deiodinase type I, which is found
mainly in the liver and kidney but in small amounts is
ubiquitously present. It is localized at the inner plasma
membrane. Under physiological conditions, approximately
30% of T4 is converted by this enzyme to T3.
The expression and activity of this enzyme are stimulated
by T3; for example, in hyperthyroidism the
activity is very high, whereas in hypothyroidism it is
very low. However, many other nonthyroidal factors
affect its activity. In any catabolic state—malnutrition,
starvation, severe infections, or metabolic or malignant
diseases—its activity is decreased and this is reflected
in decreased serum T3 levels. Another example
is drug interferences such as glucocorticoids and amiodarone,
which are potent inhibitors of deiodinases.
Stimulation of deiodinase type I can be observed with
overfeeding and/or a high-carbohydrate intake.
The activity profile of deiodinase type II is very
different. It has a very low affinity constant (Km). The
enzyme that is found in the pituitary and brain is most
active when T4 is absent. It is inhibited with increasing
T4 concentrations. It is directly implicated in the
control of serum TSH. Both enzymes attack the outer
ring of T4. The third enzyme, deiodinase type III,
deiodinates only at the inner ring, a function that can
be shared under particular conditions with deiodinase
type I. Interestingly, deiodinase type III is localized at
the outer cell membrane, and by degrading T4, it
refuses its entry into the cell.
Thyroidal production of T3 is minimal compared
with that of T4.Without iodine deficiency, T3 represents
less then 5% of the secreted T4. There are at
least two conditions where this percentage can increase:
in iodine deficiency and in hyperthyroidism.
In hyperthyroidism, the thyroidal deiodinase is
strongly stimulated so that some of the T4 is converted
during the process of secretion to T3. In iodine deficiency,
this mechanism is also operating, but the
poorly iodinated thyroglobulin (Tg) also has a high
percentage of T3 that can go up to 50% that of T4.
This contributes to a higher proportion of T3 in
serum, and the T3-to-T4 ratio can increase from the
physiological ratio of approximately 2% to 4% in
hyperthyroidism and to much higher values in severe
iodine deficiency. If selenium deficiency is associated
with iodine deficiency, the increased ratio of T3 to T4
is not seen because the lack of selenium affects the
activity of the deiodinases. Clinically, the increased
T3-to-T4 ratio was of diagnostic significance for T3
toxicosis that is now diagnosed more adequately by a
suppressed serum TSH in the presence of a still normal
free T4. For practical purposes, one can conclude that
the serum levels of T3 are influenced by many factors
other than thyroidal secretion and, therefore, are of
lower diagnostic value than free T4 values.
rT3 is the inactive counterpart of T3 and has been
advocated as a diagnostic tool, but today none of them
remains valid. Nevertheless, it is an interesting parameter
that gives a good mirror image of T4-to-T3
conversion. If deiodinase type I is inhibited, serum
rT3 levels increase. There are two reasons for this.
First, rT3 needs deiodinase type I to be degraded and
accumulates if the enzyme is low. Second, there may
be some shift of T4-to-T3 conversion to rT3.
For practical purposes, one can conclude that the
serum levels of T3 are influenced by many factors
other than thyroidal secretion and, therefore, are of
lower diagnostic value than free T4 values.

-------My thoughts are : according to the arcticle, iodine deficiency could make one T3(FT3) level elevated, and selenium deficiency could make T3 level decreased, what about deficiencies in both elements? And the difficulty of T3-T4 conversion came from the lack of enzymes-deiodinases? Why people don't focus on the enzymes (trying to add them, or activate them), but switch to taking the T3 combined therapy in the HRT?

Any thoughts?

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Avatar universal
what book??
this is really interesting. I'd like to read that book
thank you
Helpful - 0
Avatar universal
For practical purposes, one can conclude that
the serum levels of T3 are influenced by many factors
other than thyroidal secretion and, therefore, are of
lower diagnostic value than free T4 values.

Helpful - 0
Avatar universal
Yeah, I'm losing it a little on exactly what's being said in the paragraph that you pulled the above out of.  T3 is active thyroid hormone.  Keep in mind that NO receptors have ever been identified for T4...it has to be converted to T3 first.

However, I'm confused about what he's saying "the serum levels of T3...are of lower diagnostic value than T4 values".  Diagnosis of what?  Thyroid dysfunction in general?  T3 toxicosis?  
Helpful - 0
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