Where do I find the Susan Owens post?
OK, thinking through mechanisms now.
T4 needs to get into cells. That's apparently via both passive & active transport. Passive "leaks" across, and that only requires good membrane fluidity (which can be issues for some people, particularly ACAT/fat digestion & metabolism issues). Active transport goes against the concentration gradient, and that requires help. Taking a guess that for some people, the active transport breaks down, so they are reliant more on just the passive transport. Taking thyroid hormone would help in that case (even if tests are normal) because it would increase the blood concentration of hormone, which would increase passive transport - amount "leaking" into cells).
An abstract I'm using to chase down more info on the transporters:
http://www.ncbi.nlm.nih.gov/pubmed/15727804 So, two basic classes of transporters.
The first one, NTCP, can be kicked into high gear by cAMP, says here. Likely does it both by increasing transport rates (playing with ions) and translocating proteins (sticking more of the transporter proteins in the cell membrane). So hypothesis might be that cAMP is low, so not as many transporter channels in cell membranes. Low cAMP is also implicated in ADHD/autism/Alzheimer's (prefrontal cortex higher order thinking stuff). So need to learn more about that. cAMP is made from ATP - so if mitochondria don't produce enough ATP, one consequence might be less thyroid hormone getting in (which decreases ATP production even further). Yasko has stuff on increasing ATP, must go read. I'm also giving DS straight ATP (for a methylation cycle step) - maybe that would be an interesting supp for this kind of hypothyroid?
That's probably where a hormone 'jump start' can also be helpful?
Another line of thought that interests me here - these channels depend on sodium concentrations. ACE++ mutations and adrenal fatigue both result in changes to sodium retention. Wondering if early stage adrenal issues result in slowdowns of these sodium dependent transporter channels, so less thyroid hormone gets in... Shannon, any idea if it is na+ concentration inside or outside of the cells that matters for triggering this gate? And would higher concentrations slow down or speed up the gate?
Thats going to depend on if it's a symporter or antiporter. Symporters move Na+ and the hormone/whatever in the same direction, so increased sodium concentration would increase hormone transportation. Antiporters trade sodium for hormone. I always forget which way sodium and potassium go, which is inside the cells and which is outside. But the transporter might use sodium potassium pumps to work against the normal gradient, too.
Second kind of transporters, OATP class, example MCT8. Serious defects in MCT8 can cause low muscle tone and no speech. Shannon, can you see this gene in your 23andme test?
Of the two genes mentioned, there are 9 SNPs for the first and two for the second. It looks like the first is more associated with goiter and the second with resistance? I'm homo for all of the first ones (no clue which versions are normal) and no history of goiter. I'm hetero for one of the second, which seems to fit better based on labs.
Another good overview http://www.biochemsoctrans.org/bst/0...bst0330228.htm
Then T4 has to be converted to T3 in cells - if this isn't working well enough, does that show up on the standard thyroid test? So for those of us with "normal" tests, probably not the problem.
By Dr K's ranges, comparing ft3 and ft4, I show a slight pattern of underconversion. Basically, my ft3 is at the low end of lab-normal, and my ft4 is mid-range. His explanation is that it's either high cortisol blocking the conversion, or membrane damage due to inflammation/chronic infection.
Then T3 needs to bind to receptor sites. This could be where the mitochondrial damage kicks in. DNA repair is a key function of methylation, so guessing that well functioning methylation would help out quite a bit here. Might also be genetic mutations for receptor sites that are hereditary (which makes more sense to me as a mechanism for "hereditary" hypothyroidism than what Starr is proposing)