Reverse T3 is somewhat on the high side. In some cases it may outweigh mid-range T3, causing symptoms. But these would be more hypothyroid-type effects.
C, have you come across any more info on the reverse T3 "clogging up" T3 receptors hypothesis? I've only found scanty stuff, but I don't really know why people who take T4 meds would feel worse unless it were due to this.
No, I think I've mentioned that there is some skepticism regarding the receptor-clogging hypothesis. ZRT says
"Since high rT3 is linked with conditions associated with slow metabolism, it has been claimed in internet articles, but not in peer-reviewed papers, that rT3 causes a slowing in metabolism by blocking or obstructing the nuclear thyroid receptors. These receptors are the target sites where the primary active thyroid hormone, T3, binds, triggering its actions to drive cellular metabolism and maintain body temperature. Yet there is no credible scientific evidence that rT3 even enters the nucleus of the cell.
While rT3 does not bind to, and has no known transcriptional activity at, the thyroid receptor, it does have potent non-genomic activity
, mediated by binding to a specific thyroid receptor in the cytoplasm, as an initiator of actin polymerization in astrocytes in the brain . ..."
The link from Osprey is very interesting. It says "The 5'D-II [secondary T4->T3 enzyme path] in brain, pituitary, and brown adipose tissue was reduced to less than or equal to 60% of control by 30 micrograms/100 g bw reverse T3 (rT3), an effect that lasted for at least 3 h after rT3 had been cleared. In rT3-pretreated thyroidectomized rats, the generation of [125I]T3 from tracer [125I]T4 was reduced in the serum: 6 +/- 1 vs. 12 +/- 1 X 10(-3)% dose/ml, P less than 0.01, during this 3-h period."
So maybe it can be inferred that high reverse T3 can result in local T3 deficiency in certain tissues. I've been wondering what causes the possible subjective improvements I've seen in taking 10 mcg liothyronine qd. This apparently resulted from cutting rT3 in half, while free T3 didn't move, and free T4 moved lower.