Adrenal Cancer: When Your Diagnosis Is One in a Million

It wasn't the word "cancer" that scared Linda Gannon most; it was what came next: "Rare," she heard the surgeon say. "One in a million."

The oncologist Gannon saw next was also at a loss: "This is very rare, and we've never seen any cases of this."

And when Gannon, a 56-year-old retail buyer in Montville, New Jersey, made an appointment at Memorial Sloan Kettering Cancer Center -- which U.S. News ranks No. 2 in the country for cancer care -- her stomach sank yet again: "I was going to see a doctor listed under 'other cancers,'" she recalls. "I didn't have a category."

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Adrenocortical carcinoma, also called adrenal cortical cancer, ACC or simply adrenal cancer, is a cancerous tumor that forms in the outer layer of the adrenal gland. The two glands, which sit just above the kidneys, make hormones responsible for regulating stress, blood pressure and other bodily responses. While the vast majority of adrenal tumors are benign, about 600 people in the U.S. are diagnosed with cancerous, often lethal, adrenal tumors each year.

The chance of developing such a disease? It's literally one in a million.

"Most doctors have never seen a case, and even if they had, they wouldn't know what to do," says Dr. Gary Hammer, director of the Endocrine Oncology Program at the University of Michigan's Comprehensive Cancer Center, who wound up treating Gannon. He holds the endowed Millie Schembechler Professorship in adrenal cancer -- possibly the only one of its kind in the world, he says.

For patients like Gannon, who was diagnosed in 2009, the cancer's rarity often means facing blank stares from physicians and loved ones, thin -- and often terrifying -- results from internet search engines and only a single item on a "list" of approved drugs to treat it.

"These patients are like orphans," Hammer says, citing drug companies' lack of interest in investing in ACC research, "and they get left behind."

Finding the Zebra Among the Horses

When Drew O'Donoghue first complained of bad headaches in late 2012 at age 20, his father teased him. "I thought he was getting into the college life and [having] a couple extra beers here and there," recalls Sean O'Donoghue, whose son was an athlete, fraternity brother and dean's list student at Villanova University at the time.

But when the headaches persisted, the younger O'Donoghue visited his university's health clinic, where he was ordered to receive a scan that revealed a large mass near his kidney. One week after doctors removed the mass -- along with half of O'Donoghue's liver and one adrenal gland -- in a nine-hour-surgery, the family learned it was adrenocortical carcinoma. "[It] sounded Greek to me," Sean O'Donoghue remembers.

The diagnosis feels foreign on physicians' tongues, too. While ACC is too rare for most primary care doctors to consider as a potential diagnosis, there's no single medical specialty with expertise on the condition. "Adrenocortical cancer is lost between endocrinology and oncology," Hammer says, although the Endocrine Society is planning to publish guidelines on ACC management, and various cancer and surgery organizations are also getting involved. At the University of Michigan, for instance, the now-model protocol involves a multidisciplinary team including radiation oncologists, endocrine surgeons and other specialists.

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Not only is the condition extremely statistically unlikely, but it also evades prompt diagnosis because it has no giveaway symptoms. In fact, the most common symptoms -- weight gain, high blood pressure and diabetes resulting from the tumor's effect on the adrenal glands' production of key hormones -- are also "the three most common symptoms and complaints in Western society," Hammer says. The challenge for doctors, he says, "is finding the zebra among the horses."

About half the time, patients have no symptoms and are instead diagnosed haphazardly -- say, when receiving a CT scan after a car wreck or, in Gannon's case, when undergoing an ultrasound to check for kidney stones. "The technician couldn't see my kidney on the left side," she says, because it was blocked by an adrenal tumor that, weeks later, was found to be cancerous.

For many patients with ACC, a delayed diagnosis can mean progression to a late-stage cancer. Drew O'Donoghue, for one, was diagnosed at stage 4 -- a level of cancer so advanced the chances of surviving past five years are less than 10 percent. Among all patients, the five-year survival rate is about 50 percent.

Uniting for a Cure

Gannon left the first oncologist's office with three prescriptions: one for an anti-nausea medication, one for a steroid to fight inflammation and one for a chemotherapy drug called mitotane. Googling the third medication only deepened the pit in her stomach. The drug -- the only one approved to treat ACC -- is a derivative of DDT, which is now illegal for pest control. "You wonder, 'What is it doing to me?'" recalls Gannon, who continued treatments for about three years and is now cancer-free.

Sean O'Donoghue had a similar reaction to his son's prescription for mitotane. "That just seemed antiquated and just a horrific therapy regimen to go through every day." But outside of participating in clinical trials, patients like Drew O'Donoghue, who passed away from the disease in 2014, have no choice. Even removing the tumor (and the adrenal gland), which is standard protocol if the disease isn't too advanced, rarely cures the disease, since it spreads quickly to other organs and frequently recurs. Radiation therapy may also be used, but it often just delays recurrence. Talking to patients about their precarious futures, Hammer says, is "a fine line between hope and reality."

The wider ACC community, however, airs on the side of hope -- and action. The O'Donoghues, for one, launched The Drew O'Donoghue Fund to raise awareness of the condition, fund research for its treatment and eventual cure (it's partnering with Memorial Sloan Kettering Cancer Center, where Drew was treated, to support a pre-clinical research project, for example) and connect with other families coping with the disease. "Sometimes it's the small issues that can help find the key to finding an answer to the big issues," Sean O'Donoghue says.

Clinicians, researchers and institutions around the world are also partnering in ways that are practically unheard of in the world of medical research -- by sharing data sets, patient populations and findings before publication, says Dr. Martin Fassnacht, head of clinical endocrinology and diabetes at the University of Würzburg in Germany. Among the goals are to identify which patients respond to mitotane and to develop more targeted, less harmful treatments for those who don't. "The different international centers are not competing," Fassnacht says, "and this is amazing."

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For Gannon, dedicating the time and energy to run her foundation ACC C.U.R.E., which raised $25,000 in its first year alone to donate to the University of Michigan's Comprehensive Cancer Center, is the natural response to surviving a disease many don't. "[Adrenal cancer] is just as important as any other cancer, it's just as important as the research for breast cancer or colon cancer or anything else," she says. "Our mission is just as important as anyone else's."