Finding a well educated integrative, functional or a naturopathic ND ( that can prescribe) because Endo’s that depend on the TSH to determine what a “ Free” T4 or “ Free” T3 not a total or an uptake is negligence out of pure ignorance.
In thyroid disease and therapy, even when TSH is normalized, we can still be genuinely hypothyroid if we do not have enough “Free” T3 getting into our thyroid hormone receptors in cells throughout the body.
Most people know there’s two ways we get T3 into our cells’ nuclei:
- From circulating Free T3, and
- From circulating Free T4 hormone that is converted into T3 at a variable rate.
However, most doctors are not taught about our cells’ and tissues’ high priority for and dependence upon circulating T3, nor are they taught about the largest factor that can reduce T4’s local variable conversion rate to T3, nor are they taught about the direct correspondence between Free T3 levels and T3 nuclear occupancy rate, which determines hypothyroid or euthyroid status both locally and globally in the body.
The body’s dependence on a baseline of healthy circulating T3 is a principle that Antonio Bianco has emphasized in numerous publications.
“ T3 and T4 cannot enter cells by passive diffusion. As they enter the cell, they must be carried on transmembrane thyroid hormone transporters, some of which have a relatively higher preference for T3 and others which have a relatively higher preference for T4.
- T3 hormone does not need to be converted. It is already in the active form, ready to bind with receptors. If it is not inactivated to T2 by D3 enzyme expressed in the cell (D3 is not shown in this diagram), a large percentage of T3 entering on transporters can be ushered directly into the nucleus.
- Circulating Free T3 fills the bottom layer of the gray sphere of nuclear receptors. Of course, nuclei don’t have “layers,” but TRs are distributed throughout the nucleus. This visually depicts the fact that each tissue depends on a baseline amount of circulating T3.
- Deiodinase type 2 (D2) enzyme activity (and in other cells, D1, not shown) converts T4 hormone locally into T3, but at a highly “variable rate” because D2 will be progressively deactivated as T4 rises within reference range. (Analogy: You can imagine that the D2 enzyme is like an office worker who gets overworked and discouraged when too much T4 paperwork gets put on his desk that requires processing.)
- T3 converted locally from T4 tops up T3 levels within the nuclear compartment. T4 is the second priority source for T3, a source that enables customization of T3 availability from tissue to tissue, as long as D2 and D1 enzymes can convert T4 locally at a healthy rate. The cell is simply not equipped to make extra T3 supply locally from converted T4 if or when FT3 supply falls short. T4 is nature’s version of “sustained-release T3” except that T3 production is highly variable.
- In this particular tissue, a certain percentage of “unoccupied receptors” is necessary for euthyroid status. If too many of the unoccupied receptors are occupied, it will create localized thyrotoxicosis. If too few are occupied, the tissue will be hypothyroid. Therefore, T3 hormone sufficiency is the ultimate determiner of euthyroid status throughout the body.
- The T3 bound to receptors will enable genomic signalling. In this cell located in the pituitary thyrotrophs, T3 will perform genetic transcription of TSH mRNA (see the arrow under the gray sphere), which, together with TRH hormone from the hypothalamus, co-regulates the level of TSH hormone secretion. In a different tissue or organ, T3 binding will signal to different genes that enable other essential biological processes to occur.
- After binding with TRs for 30 minutes to several hours, each T3 molecule exits the nucleus and returns to the cell’s cytosol (the green area in the model).
- The ratio of T3 and T4 hormones floating in the cytosol is then transported out of the cellby the same thyroid hormone transporters that brought T4 and T3 into the cell (exit transport is not shown in the diagram). The rate of hormone influx matches the rate of hormone efflux, much like breathing in and breathing out.
- This means that intracellular T3 and T4 ratios and levels directly affect FT3 and FT4 concentrations in blood. There is no “secret compartment” for T3 in the body, no “black hole” that sucks up T3 and never lets it go back into blood. There are only different rates at which each tissue exchanges hormones with blood, and one “global” rate of exchange that is comprised of the net rate of all tissues. The body converts and recycles T3 and T4 hormone among many cells and tissues until they are converted to other thyroid metabolites and/or excreted from the body”
despite weight loss.
