That I know of - if the tune was set with a vacuum leak, the tune will need to be redone. The same goes for throttle body sizes - if you adjusted the size then the tune will need to be updated to compensate.
Also, have you checked your MAF sensor? Clean the sensor with MAF sensor cleaner.
Are you able to check your fuel trims? They can be a useful tool. Like KS03 said, a leaking fuel pressure regulator can cause issues. Have you tested fuel pressure when the truck is off? Does it maintain pressure, or do you see the fuel pressure dropping?
If you unplugged the throttle body, you may need to do an idle relearn on the truck.