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Removing tumor from a tricky part of brain, surgeon gives teen his life back

After years of practicing surgery techniques in a part of the brain known as a “no man’s land,” Juan Fernandez-Miranda was able to remove a complex pituitary gland tumor from a Lebanese teenager.

- By Gordy Slack

Juan Fernandez-Miranda was able to fully remove a pituitary gland tumor from Ali Daoud after the teenager underwent two unsuccessful surgeries in Lebanon.
Courtesy of the Daoud family

In the summer of 2019, Ali Daoud, then 14, had just completed middle school in Baabda, a neighborhood on the outskirts of Beirut, Lebanon. He liked to hang out with his friends, swim and play soccer. He also read voraciously. Physics and math were his passions. He graduated first in his class and was looking forward to high school.

As summer progressed, though, instead of growing taller and stronger like his friends, he was getting heavier and weaker. He also was having uncomfortable heart palpitations, which accompanied a deepening sense of anxiety. By the time he started 10th grade, Daoud had gained 40 pounds, and his face had grown round and fat. He also had painful shingles and ascending a flight of stairs exhausted him.

On the other side of the world, Juan Fernandez-Miranda, MD, professor of neurosurgery at Stanford University School of Medicine, was in his lab, poring over human head specimens, dissecting them like Leonardo da Vinci five centuries before, to explore the anatomy of a 1-square-centimeter section known as the cavernous sinus. Learning to safely approach the cavernous sinus and to work within it had become something of an obsession of Fernandez-Miranda’s; he wanted to help patients whose tumors had invaded the area. That preoccupation eventually paid off for Daoud, but not until doctors were able to zero in on the cause of the young man’s symptoms.

Ailing in a troubled land

Because of his weight gain, Daoud said, he was bullied at school. Trying to slim down, he stopped eating all but one modest meal a day. His mother, ZN (who asked that her full name not be used), took Daoud to a pediatrician, who attributed the boy’s symptoms to stress.

There was a lot to worry about that fall. Lebanon’s national debt had ballooned, the country’s politics was in gridlock and the value of its currency was in freefall. Annual inflation was exceeding 80%, and protests were roiling the streets.

Daoud’s mother knew stress wasn’t the root of the problem, but she took him to a psychologist in hopes of addressing his anxiety and depression. Therapy didn’t help, she said.

Daoud combed the internet for explanations of his strange symptoms. He concluded that he had Cushing’s disease, a rare disorder caused by overproduction of the hormone cortisol. When he mentioned it to his doctors, he said, they didn’t take him seriously.

Ali Daoud waits to see a physician at a clinic in Beirut in December 2019. He correctly diagnosed himself as having Cushing's disease months before his doctors agreed.
Courtesy of the Daoud family

One day in September, while in class, Daoud had abdominal pains so intense he was rushed by ambulance to an emergency department. He was treated for acute constipation, extremely low potassium and high blood pressure, but it wasn’t until January 2020 that an endocrinologist confirmed Daoud’s self-diagnosis. A tiny tumor on his pituitary, the pea-size gland at the base of the brain that governs the production and release of hormones, was causing a cortisol deluge, resulting in Cushing’s disease.

Too much cortisol — sometimes called the stress hormone — causes blood pressure and heart rate to rise and leads to weight gain in the face, abdomen and chest; irregular hair growth; diabetes; radical mood swings; and a suite of other distinctive and sometimes lethal medical problems.

Daoud needed surgery to remove the tumor. Just a few weeks after his diagnosis, he underwent an endoscopic surgical procedure at a hospital in Beirut: A surgeon entered his skull through his nose and sinuses using surgical tools and a tiny camera — an endoscope — to locate and remove the growth. After the operation, Daoud’s surgeon reported that he’d removed the entire tumor; although Daoud’s cortisol level remained high immediately after surgery, within a few days it began to drop, and his symptoms abated. “We thought I was going to get my life back,” Daoud said.

He regained his physical, emotional and social footing. But in the summer of 2020, his symptoms reemerged. “It all rushed back! I’d spent the last seven months believing a great lie that I was healed,” Daoud said.

A second surgery was scheduled, this time with one of the Middle East’s most renowned neurosurgeons. While Daoud and ZN waited, a huge explosion at the Port of Beirut killed and injured thousands.

Unfortunately, Daoud’s second surgical procedure — also conducted in Beirut — had the same outcome as his first, except that this time, the symptoms returned more quickly.

Leveraging every contact she had, Daoud’s mother began sending letters to friends and friends of friends overseas, asking for help. Eventually, she learned about Fernandez-Miranda. Daoud wrote the doctor a long letter with a detailed account of his medical history. The surgeon was impressed by the young man’s evident intelligence and his determination to get treatment, and he agreed to review Daoud’s images and files. When he did, he immediately ascertained why Daoud’s first two surgeries had failed. He also knew that he was singularly well equipped to help. If ZN could get Daoud to Stanford, Fernandez-Miranda told her, he would find a way to remove the remains of his tumor.

‘No man’s land’

The pituitary gland sits in a small bone cave, called the sella turcica, just behind the sinuses. Parts of Daoud’s tumor had penetrated the cavernous sinus, directly adjacent to the sella turcica. Only a thin membrane, the medial wall, separates the pituitary from the carotid artery, and Daoud’s tumor was growing in a corner of his sella turcica next to the medial wall. If the tumor was clinging to or penetrating this membrane, it would explain why Daoud’s other surgeons had left traces of it behind — or perhaps had not even dared look for it there.

A month after Juan Fernandez-Miranda removed Ali Daoud's tumor, the teenager's Cushing's symptoms were gone. Fernandez-Miranda said there was a 99% chance Daoud was cured.
Courtesy of the Daoud family

In his more than a decade dissecting brains in his Stanford micro-neuro-anatomy lab to discover and practice safe approaches to this half-a-cubic-inch area, Fernandez-Miranda had learned how to find the medial membrane’s anchoring points (like “tent stakes,” he said) and tease them apart from the carotid artery without harming the vital structure. He has approached the area from every possible angle and internalized every aspect of each successful approach, rehearsing, he said, until operating there is second nature.

Back in Lebanon, after contacting Fernandez-Miranda, ZN and Daoud pored over two of his papers, the first describing his extensive studies on the anatomy of the cavernous sinus, the other describing his remarkable success with 50 patients who had tumors much like Daoud’s. While other surgeons to whom ZN wrote in the United States and France estimated their success rates between 0% and 40%, Fernandez-Miranda’s paper showed his to be greater than 90%.

“We could see that he had found a way to get these tumors safely but completely out of patients by his intensive training in the anatomy lab,” Daoud said. “You don’t see many other surgeons practicing like that.”

Daoud and ZN were determined to get Daoud to Stanford and put him under Fernandez-Miranda’s practiced hand. The U.S. embassy in Lebanon was closed, the pandemic was raging and Lebanon was teetering on the brink of civil war. But they managed to secure an emergency medical visa and, on May 20, Daoud and ZN flew to the United States. Less than a month later, on June 14, Fernandez-Miranda performed Daoud’s third surgery at Stanford Hospital.

Fernandez-Miranda inserted an endoscope and surgical tools of his own design into Daoud’s nostrils, navigating his way through the teen’s sinuses to his skull base, the area just behind his nose. From there, it is only a short distance to the sella turcica and the pituitary gland. He found no tumor there. “I knew it must be hiding on the ‘dark side’ of the medial wall of the cavernous sinus,” he said.

At that point, his decade-plus of experience, dissections and immersive study paid off. He made another approach, this time from the cavernous sinus side.

“When I opened the membrane into the cavernous sinus and saw the remains of Ali’s tumor, I said, ‘Voila!’ I knew immediately that when I removed it, I would improve the life of this extraordinary young man forever,” he said.

The entire operation took about four hours. Unlike Daoud’s first two surgeries, on the day following the procedure, his cortisol levels plummeted. “If the patient’s cortisol levels drop like Ali’s did, the chances of being in long-term remission — meaning cured forever — are 99%,” Fernandez-Miranda said. “Immediately knowing the outcome of an operation is just amazingly gratifying.”

Daoud was in the hospital for three days. He is still recovering, as his cortisol levels are low — to be expected, Fernandez-Miranda said — which causes some fatigue. But that will pass, the surgeon said; Daoud’s pituitary gland will regain the normal productions of cortisol now that the tumor is gone.

The Cushing’s symptoms are no more, and that makes all the difference. “I’m sleeping better, am no longer constipated, no longer have heart palpitations, no more high blood pressure,” Daoud said. “I look forward to going back to school, making new friends, enjoying life to the maximum. I can’t wait to do the things my muscle weakness prevented me from doing before. Especially swimming!”

While Daoud’s prospects are much better now, his country is still in crisis. He and his mother are awaiting return to Lebanon, where they know life will be difficult. “In Lebanon right now, the situation is catastrophic. We have shortages of medication, of gas, of electricity. You can’t even find Tylenol,” Daoud said. But he is now in much better shape for whatever he’ll have to face back home.

“We are expecting great things from Ali; he has a bright mind and a brilliant future,” Fernandez-Miranda said.

Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

2021 ISSUE 2

Unlocking the secrets of the brain

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