One possible plot could be that Naruto's loss of sanity causes him to have a distorted view of the Fem Kyuubi. Maybe he sees her as both a threat and a source of power he can't control. This could lead to a conflict within himself as he battles his inner demons while also interacting with the Fem Kyuubi in unexpected ways. For example, instead of the usual relationship of cooperation or taming, he might try to completely dominate her, which would be a big shift from the normal Naruto we know.
Other characters in the Naruto universe might also be affected. For example, his friends like Sakura and Kakashi would notice the change in Naruto. They might try to help him, but their attempts could be in vain because of the complex situation with the Fem Kyuubi involved. This would create new tensions and storylines as they struggle to deal with a Naruto who has lost his sanity and the mystery of the Fem Kyuubi's role in it.
The fem Kyuubi might feel a sense of protectiveness. Seeing Naruto without his mask could make her realize how vulnerable he is. She may then use her powers to safeguard him from any potential threats that could take advantage of his exposed state.
Maybe Orochimaru manages to get his hands on Naruto and subjects him to some dark and twisted experiments. These experiments could mess with Naruto's mind, causing him to lose his sanity. He could start seeing illusions all the time, believing his friends are his enemies. As a result, he'd be in a constant state of confusion and aggression, and his once - positive attitude towards life and ninja - hood would be completely gone.
If Naruto loses his mask in this fanfiction, it might change the power dynamics. His identity being more exposed could make him a target. The fem Kyuubi might have to step up and use her powers to protect him. This could lead to a closer bond between them, and they might start to rely on each other more in the face of new threats.
It could be Kaguya. If Kaguya were to return and use her powerful abilities to drive Naruto mad, perhaps by invading his mind with dark thoughts and memories. She has the power to warp reality and minds, so she could easily make Naruto lose his sanity. And since she has a grudge against the world of ninjas, making Naruto, one of the most powerful ninjas, go insane would be a great way for her to start her reign of terror all over again.
Often in such fanfictions, the plot may involve a betrayal that pushes Harry over the edge. It could be a friend or a mentor who turns on him. This sudden shift in loyalty would shatter his world view. He has always relied on the support of those around him, and when that is taken away, it becomes difficult for him to stay sane. His actions would then become erratic as he struggles to come to terms with this new and cruel reality.
One great fem Naruto x fem Kyuubi fanfiction could be one that focuses on their unique bond. It might explore how they interact in a world where Naruto is female and the Kyuubi also takes a female form. For example, it could show them teaming up against common enemies and how their combined powers are different from the original story.
Perhaps an unknown and powerful dark ninja. This ninja could be from a long - forgotten clan with dark powers. They might have a vendetta against the Leaf Village and see Naruto as the key to their revenge. So they use their dark arts to make Naruto lose his sanity and turn him against his own village.