Small: having to deal with a long period of absolutely nothing and constant nagging that you may not be good enough / doing something wrong / etc. Most people do very poorly with prolonged periods of almost no feedback.

Large: dealing with managing large amounts of social relationships of a community which, let's just say, likes pushing a lot of fringe demands and just a lot of demands in general. Also having to be 'online' almost all hours, until the point you're big enough to ignore it and take the hit.

That's about it. Small streamers don't have communities big enough to have to worry about everything yet, even if they might. Large streamers have the means to be more akin to bosses of small teams than lone workers, offloading minor tasks and instead handling finances (which many still don't, at most having an editor). Large streamers (500+) are far more 'ingrained' than most commenters give it credit for: as long as your quality doesn't drop, you can coast by on what is a very free and easy job, selling out a few times a year. It's getting there that is the problem.

And for about any of the points mentioned, you could find a parallel with startups, bosses, freelancers, independent contractors, managers, etc. It's more the combination that is unique than anything else.