Investors reacted with concern that Steve Jobs' departure on medical leave from Apple ( AAPL) could delay key new product introductions and add long-term uncertainty about the direction of the company he founded. Apple's decision to put out the statement on a U.S. public holiday with markets closed left investors to register their fears in Frankfurt, where Apple has a secondary listing, sending the US group's shares down as much as 8%. Jobs, 55, gave no timetable for his return from his second medical leave of absence in two years. He is keeping the chief executive title, but is again handing off responsibility for the day-to-day running of the business to Tim Cook, chief operating officer. While Cook drew wide praise for running Apple as interim chief executive in the first half of 2009, during Jobs' last medical absence, it was only after the founder's return that Apple introduced the much-heralded iPad. "Unfortunately, even Steve Jobs isn't superhuman. There may come a point where health problems necessitate a change in leadership," says Noah Elkin, an eMarketer analyst. "Everyone knows at some point it will happen." Apple declined to say what was wrong with Jobs, fueling speculation that his cancer had returned. An earlier recurrence of a rare type of pancreatic cancer was the presumed reason for his liver transplant in 2009. Liver transplants fail to completely remove similar tumors as much as 30% of the time, according to cancer specialists. Apple's failure to specify a return date for Jobs this time round has served to heighten speculation that he may not return. During his 2009 leave, Apple said Jobs would be absent for six months; in fact he returned more than a week early. "I love Apple so much and hope to be back as soon as I can," Jobs said in an e-mail to staff. "In the meantime, my family and I would deeply appreciate respect for our privacy." He continued: "I have great confidence that Tim and the rest of the executive management team will do a terrific job executing the exciting plans we have in place for 2011."