I've had responses from people at the lower end of your 20k-100k sub range, but never messaged anyone with 50k+ that I can think of. I suppose it depends what you write, if it's an essay or a blatant attempt at personal gain without giving anything back then you're going to get ignored, but if it is something sensible and related to their content I would hope for a response.
This all assumes of course that they don't get so many messages that they've turned off email notifications and never check their YouTube inbox...