I suspect that this is because when someone asks me this, they are requiring me to respond to a question and yet they have no real interest in the answer at all. Yet I understand that their feigned interest is more automatic than it is rude. It is a social question, one that is expected of people to ask of their friends and acquaintances, the latter in more of a passing way rather than out of any real interest in the answer.
However, that said, I've started to respond to the question in more of a humourous fashion. In answer to the question, "How are you?", I respond with, "I can't answer that." When people ask me why not, perhaps fearing the worst, I respond, "Because of the Medical Privacy Act", and that gets a good laugh.
And when asked "What's up?", I don't lie about it. "My blood pressure, cholesterol, and BMI (body mass index)!" This gets a good laugh, too, but it doesn't necessarily lead to any other questions about my health and all...and that's the way I prefer it these days.
In a twisted sort of way, this just goes to show that Laughter is indeed the best medicine. Most of the time.
I feel much less peeved now. :)