To add to volsfan846 comments on experimentation, If you are drilling for comfort, it is best to pitch holes in the direction you are having issues.
For instance, if you are feeling pressure, callusing, etc. on the side of your thumb closest to your index finger, try pitching your thumbhole a little bit more in that direction.
For example, if you are currently using 1/4" towards the palm and are feeling pressure on the index finger side of your thumb, try changing your pitch to 1/8" towards the palm. If you are still feeling pressure, go another 1/8" to zero lateral. Keep experimenting until you get the feel you desire. Which, to me, is equal pressure from side to side and front to back. And that is not just for the thumbhole. That also means fingers too.
One other point to make. Please make sure and have your grip checked at least every other year by a reputable Pro Shop operator in your area. As we all know, our bodies change as we get older. This includes our hands also.
There Brunsrick. Now go get some sleep.
Verbswick