"POTUS" stands for "President of the United States." Other acronyms in this vein include "FLOTUS," referring to the First Lady of the United States, and "VPOTUS," the Vice President of the United States. SCOTUS is also popular as an acronym for Supreme Court of the United States.
President Franklin D. Roosevelt is said to have first assumed the name POTUS in wartime correspondence with Prime Minister Winston Churchill of the U.K. It may also have originated from the 1997 White House fiction novel, "Full Disclosure," and it is now used by the Secret Service and White House staff. It is not generally used in direct discourse with the president.