Here's a table when you need to take a campaign U turn.
1. A beloved NPC turns up dead the next morning.
2. A God falls from the sky, dead. It rains ichor.
3. A strange magical portal appears on the side of a building or animal
4. A note from a loved one is under a PCs pillow, a relative has died.
5. Dragons no longer have the ability to breath fire.
6. The local town is taken over by mysterious travelers, on the outskirts is a large metallic craft.
7. A large vein of gold has been found, rendering the gold piece completely insignificant.
8. A famine has taken over, people are hungry, begging in the streets.
9. A tax collector has been strung up at the gates of the city.
10. Large holes in the ground have started appearing, someone claims they are really deep.
11. The night has come, the sun doesn't rise the next day or the day after.
12. Alcohol no longer has any effect on anyone.
13. Wishes come true, even the insignificant ones. But only for 2 days.
14. A herd of mechanical cows come stampeding across the local fields.
15. People are waking up from the dead, they are not undead and not zombies, they resemble themselves the day they died.
16. Locally grown mushrooms if ingested allow a person to time travel back one day.
17. A ingenious alchemist invented gun powder by accident and burnt half the town down.
18. A the local militia have mysteriously fell ill. A barbarian tribe has encircled the town.
19. It has not stopped raining for days.
20. All forms of birds have been found dead. Sometimes falling from the sky.