How many doctors does it take to solve a medical mystery? In this patient’s case, the answer is six

As an orthopedic oncologist, Roberts agreed with Hall that imaging didn’t show evidence of cancer. When Roberts met with Karim, Karim mentioned that a radiology tech originally from Australia had suggested that his symptoms sounded like a bone disease called osteomalacia; Karim noted that an assistant in Roberts’ office had also brought up the condition. The doctor agreed that it sounded plausible.

Roberts’ thoughts turned to a patient or two he’d seen years ago during his sarcoma surgery fellowship with a form of the disease called tumor-induced osteomalacia (TIO), an ultrarare condition that most doctors never encounter in their careers. It’s estimated that only a few thousand people in the U.S. have this endocrine disorder, which is exceptionally hard to identify because the tumor that causes bones to demineralize and break down is tiny and can be anywhere in the body. Like the patients Roberts remembered seeing during his fellowship, Karim had widespread bone deterioration, in his hips, ribs and sacrum. “Clearly something systemic is going on,” he told Thurlow.

Melting bones 

Roberts called Hall.

“It’s been a long time,” Roberts said, “but from what I remember from my fellowship, you need to order a specific blood test, serum FGF23.”

The test detects the presence of fibroblast growth factor 23, a hormone that bone produces. The hormone helps maintain bone health, but when it’s overproduced, chaos ensues. Too much FGF23 blocks the conversion of Vitamin D, which has the effect of dissolving bone like cookies in milk. 

In healthy skeletons, bones are alive, constantly disintegrating and being rebuilt. But too much of the hormone tips that balance, and bones lose their structure and integrity, breaking and causing excruciating pain.  

Hall was intrigued, especially after he ordered the blood test and the results returned overwhelmingly positive. It appeared that Karim had what’s known in medicine as a zebra — the rarest of rare occurrences, the kind that Hall can’t recall learning about in his medical school textbooks. Every medical student learns that when they hear hoofbeats, they should anticipate a horse cantering around the corner, not an exotic zebra. But Karim’s case bucked the trend. 

Now the focus shifted. If Karim did indeed have TIO, what kind of tumor was wreaking all this havoc? And where was it?

“We realized we needed a whole-body picture because these tumors can be tiny and hard to see,” Hall said. 

That's where Delphine Chen, MD, director of molecular imaging and therapy at Fred Hutch, entered the picture. Chen heard about Karim’s case during a tumor board, a regularly scheduled meeting of multiple cancer specialists to dissect unusual cases and land on a treatment plan. Chen suggested a full body PET/MRI scan, using a specialized scanner that is typically available only at academic medical centers such as Fred Hutch. Chen recommended using GA-68, a radioactive isotope, paired with dotatate, a peptide, to create a good picture of the somatostatin receptor. That receptor is present in tumors that cause TIO, so it proves helpful in locating these tumors.  

“Our team found the area really easily,” said Chen, who holds the Wil B. Nelp, MD Endowed Professorship in Nuclear Medicine at the University of Washington School of Medicine. “We could see it on the scan — a really bright spot in his right thigh, right next to the bone.” 

‘We found it’ 

Chen had found the tumor, and the scans had revealed numerous subtle fractures in many parts of Karim’s body. But Hall knew that more treatment was necessary.

“We found it, so that was a crucial first step,” Hall said. “But we still didn’t know what kind of tumor it was. And his bones were literally melting away. There was major urgency to reverse the impact this was having on his bones.”

In June 2023, Roberts operated on Karim to remove the tumor. Hall expected that the pathology would show some type of phosphaturic mesenchymal tumor, an umbrella term used to describe tumors that overproduce and secrete FGF23. Yet post-surgery, the tumor was classified as a spindle cell hemangioma, a connective tissue tumor often considered benign.

In Karim’s case, the tumor appeared to be benign — it was not metastatic kidney cancer, as had originally been feared — but it was clearly ravaging his skeleton, demolishing his body bone by bone. He felt a little better after surgery but not much, which was strange. Usually with TIO, cutting out the tumor is like magic; within days, the patient feels better. 

But Karim's pain persisted. In fact, it intensified.

“Months went by and it kept getting worse, not better,” Karim said.

As he waited for the pain to resolve, Karim read hundreds of case studies and grew increasingly convinced that something remained seriously wrong. An endocrinologist urged patience, but after a year, bloodwork confirmed that Karim’s FGF23 levels had jumped. A second PET/MRI scan found another tiny bright spot next to Karim’s spine. Removing it surgically would have been tricky because it had lodged near the junction of rib and spine. Once again, the specialists at Fred Hutch conferred.  

Thurlow suggested ablation, a process of destroying tissue using heat or cold. He thought the location of the remaining tumor lent itself to this procedure, but he knew this was a highly technical case that required support. Thurlow is trained to go through bone to reach tumors. But Thurlow thought a modified approach might be better. He consulted colleagues around the country and decided the best strategy was to “go through the lung, stab it and freeze it.” He also had an idea of just the person to handle such delicate maneuvering. He reached out to Grace Laidlaw, MD, MS, an interventional radiologist at Fred Hutch. 

Laidlaw specializes in treating tumors in a minimally invasive way, guided by imaging. In early 2025, working alongside Thurlow and under live CT scan guidance, Laidlaw inserted a long needle through Karim’s chest wall and into his lung until the tip reached the tumor. Only then did she begin freezing the tumor by piping argon gas through the hollow needle, freezing the surrounding cells in a process called cryoablation. When argon expands quickly, it reaches a teeth-chattering -100 degrees Celsius. Once the gas stops flowing, the affected area thaws; ice crystals that have poked holes in the surrounding cell membranes cause the dead tumor cells to rush out into the adjacent tissue. The tumor is a goner. 

“I do a lot of ablations, freezing tumors inside the lung,” said Laidlaw. “The unique part was going through the lung to get to something outside the lung. I hadn’t done that before.”

Solving the puzzle  

A few days after the procedure when Thurlow saw Karim in clinic, Karim had turned the corner.

“He said, ‘I don’t want to say it because it can’t be real, but I feel better than I have in years and years,’” Thurlow recalled. “We shared hugs and tears. 

“This is why I love my job — putting a puzzle together and helping someone who is miserable is why I do what I do,” Thurlow said. “That’s why we all do this work. For patients with this problem, no one is going to put these pieces together just on their own. It’s a very rare diagnosis, but once everyone comes together and you compare all the information, it fits perfectly.”

The diagnosis and treatment required collaboration from teams that don’t often work together: endocrine, medical oncology, orthopedics, nuclear medicine, radiology and rehabilitation. “Fundamentally, people wanted to help,” said Hall. “With each question asked, we learned more.”

Since his second procedure, Karim has gone from a wheelchair to walking three miles per day, although chronic fatigue and brain fog still limit his activity. 

Hanna Hunter, MD, medical director of cancer rehabilitation, has supervised Karim’s recovery. When she first saw Karim in June 2023, he was able to walk only a few feet around his home. Hunter recommended body weight exercises like heel slides while lying in bed and seated marches that required Karim to lift his leg an inch or two off the ground. She got him connected with a physical therapist at Fred Hutch to work on getting in and out of chairs and bed safely. 

Since his ablation, Karim has made huge progress, walking multiple miles and doing squats and jumps to build back muscle. 

“We see patients with bone metastasis or fractures but not with his condition or severity. There is no perfect set of exercises for his condition, but he has not given up,” Hunter said. “He looks like a new person.”

Karim is grateful for the degree of collaboration among specialists and wonders if it might inspire the establishment of a dedicated rare disease team that unites a broad spectrum of providers to review unusual cases and “see what bubbles up.” 

“It’s an invaluable lesson not just for patients but also for providers in terms of how important it is to have multidisciplinary care,” he said. “We never would have landed on the diagnosis without that. After all, just because you’ve never seen a zebra before doesn’t mean that someone else hasn’t.”