The perverse joke of the hackers over Apple CEO Steve Job's 'demise' apart, speculations are rife over the exact nature of the disease this high-profile IT man is suffering from.
Jobs, in an open letter signed "Steve," said earlier this week he had already begun treatment for the condition, that he would remain on as Apple CEO during his recovery, that he expected to be noticeably improved in a matter of months.
"As many of you know, I have been losing weight throughout 2008. The reason has been a mystery to me and my doctors. A few weeks ago, I decided that getting to the root cause of this and reversing it needed to become my #1 priority.
Fortunately, after further testing, my doctors think they have found the cause - a hormone imbalance that has been "robbing" me of the proteins my body needs to be healthy. Sophisticated blood tests have confirmed this diagnosis.
The remedy for this nutritional problem is relatively simple and straightforward, and I've already begun treatment. But, just like I didn't lose this much weight and body mass in a week or a month, my doctors expect it will take me until late this Spring to regain it. I will continue as Apple's CEO during my recovery."
What Job talks about is not the usual kind of pancreatic cancer that arises from the pancreas cells that churn out digestive enzymes. Those more typical cancers all too often kill rapidly.
Jobs' cancer grew from islet cells, the 2 percent of pancreas cells that make insulin and other hormones important in the conversion of food to energy and body mass. These islet cell, or neuroendocrine, tumors typically grow slowly. They can sometimes be cured with surgery of the type Jobs had in 2004.
And not uncommonly, these cancers can recur years after the first diagnosis, often in the liver.
Most doctors are perplexed by the statement. "There are probably 30 different disorders that can cause malabsorption, and some of them could be related to cancer or treatment, said Dr. Margaret Tempero, a pancreatic cancer specialist at University of California-San Francisco.
"I think it would be misleading for anybody to conclude that this is just an isolated hormone imbalance leading to a nutritional disorder," said Dr. Jeff Mechanick, chair of the nutrition committee of the American Association of Clinical Endocrinologists and clinical professor at Mount Sinai in New York.
More likely, Mechanick said, Jobs' weight loss is due to complications from his prior surgery. Such complications may occur years later.
A healthy pancreas is critical to proper digestion, producing hormones and secreting digestive enzymes that break down fats, proteins, and carbohydrates.
Removing a pancreatic tumor involves taking out part of the pancreas, bile duct and small intestine, and such a major surgery often leaves patients less able to absorb nutrients.
In addition, surgery can cause adhesions, or "kinks," in the intestine. If a part of the intestine gets blocked off, too many bacteria can grow in the tube and lead to a syndrome called "malabsorption," similar to the condition Jobs describes in his letter.
A recurrence or progression of Jobs' cancer could also cause inability to absorb nutrients, doctors said. Islet cell tumors are known to produce hormones that can produce a wasting syndrome.
However, since Jobs said he expects to regain weight by spring, it's conceivable that his weight problems are a result of surgery instead of a recurrence of the tumor, said Simon Lo, director of the pancreatic diseases program at Cedars-Sinai Medical Center in Los Angeles.
Jobs is reportedly a vegetarian, but doctors said his diet alone was unlikely to be responsible for the dramatic weight loss.
Depending on what's causing his weight loss, doctors said Jobs could potentially recover by spring with proper nutrition and pancreatic enzyme supplements.
"If it's just an issue of malabsorption and he needed to just adjust his diet and get healthy," Mechanick said, "this could be reversible and he should enjoy a recovery."
Dr. Clay Semenkovich, chief of endocrinology, metabolism and lipid research at Washington University in St. Louis, says if he saw a patient with Jobs' history and chronic weight loss, "the first thing I'd worry about is whether this tumor had somehow metastasized."
That's because the errant tumor cells can churn out prodigious amounts of the hormones their noncancerous ancestor cells produced — hormones such as insulin, glucagon and somatostatin.
"All can be associated with weight loss, diarrhea and protein wasting," Semenkovich says.
But these metastases can pose a diagnostic problem for doctors because they're often not visible on the most sophisticated abdominal scans.
When specialists suspect an islet cell metastasis and the CT, MRI and PET scans are uninformative, they often turn to fancy blood tests called "dynamic stimulatory tests." They inject substances that stimulate abnormal hormone secretion and then watch how the patient responds.
"That could give you a hint that somebody is making inappropriate levels of hormones that are antagonizing your ability to store nutrients," Semenkovich says.
When doctors find such a situation, they need to know what hormone is being overproduced in order to treat the problem. Too much insulin will lead to weight gain, because insulin causes the body to store calories.
A tumor that's cranking out too much glucagon — a sort of anti-insulin — can cause problems with protein metabolism. It causes the breakdown of protein stores, and the amount of protein in the diet can't replace the amount being broken down. That can produce chronic weight loss.
These so-called "glucagonomas" often cause a telltale, hard-to-miss skin rash — but not always.
Treatment for this type of recurrence is fairly straightforward: injections of a synthetic hormone called octreotide. This mimics the hormone somatostatin, suppressing production of glucagon and other hormones.
Whatever the course of treatment, cancer specialists and endocrinologists stress that people with other types of metastatic islet cell tumors often do well for years — and have a good quality of life — even if the cancer cannot be cured.
If they respond to treatment, "these tumors don't tend to get massive and very injurious to health the way the standard kind of pancreatic cancers do," Jensen says.
Of course, Jobs may not have a metastatic islet cell tumor at all!
There are three medical threads running through the statement, said Robert Lustig, a prominent neuroendocrinologist at the University of California, San Francisco — and they "don't add up to a very strong cable."
First is the hormone imbalance, suggesting an endocrine problem. Second is Jobs' loss of protein. He doesn't attribute this to loss by urination, which would suggest a plasma-cell cancer called multiple myeloma, or loss by defecation, which would implicate his pancreatic cancer history.
If Jobs' weight loss were related to the latter, said Lustig, he would likely display other symptoms, including severe flushing and massive diarrhea, which have not yet been described.
The third thread is the "straightforward" remedy for his "nutritional problem." According to Lustig, that conflicts with the rest of Jobs' statement. "Endocrine problems are not nutritional, and vice versa," he said.
"Hyperthyroidism can cause weight loss. Endocrine deficiency could cause weight loss. But they don't rob your body of proteins, and the remedies aren't nutritional." Neither would nutrition suffice to treat cancer.
"There's no way to put these threads together," said Lustig, though he refused to rule out a cancer-related complication. "It's not possible to dismiss anything in terms of this," he said, and called speculation "very silly."
Apple stock, which has suffered along with the wider market in recent months, rebounded sharply in pre-market trading apparently on sentiment that Jobs does not have a life-threatening condition and that he will helm Apple for many years to come.
In a separate statement Apple's board said the company is "very lucky to have Steve as its leader and CEO, and he deserves our complete and unwavering support during his recuperation."