600 micrograms, the ratio is 1.7, in other words, a 70 percent increase, and then looking at the two lower doses, they're superimposable.
Now, the question is, how does TSH respond to these relatively small perturbations in T4? That's shown here. It's a very dramatic change. The point we want to make here is for a very small perturbation in T4, TSH is excellent in distinguishing small changes. There is pronounced hysteresis, but the bottom line is that TSH is a very good discriminator and it adds biologic context. After all, why are physicians using TSH in their management of patients?
Going back to the horizontal correction procedure, this is a typical dose that I've simulated here. The red line is what we expect is happening to endogenous levels based on a NONMEM fit. Here's the horizontal correction procedure there in blue.
The points that we can make here is that it's biologically inconsistent. The baseline is probably not flat and it's not variable.
If you use this procedure, you've reduced the true area by 10 to 15 percent and that will result in