A New Take on Cushing’s Idea
In 1911, a middle-aged man walked into Hopkins because his GP thought that neurosurgeon Harvey Cushing might be his best hope. The patient had signs of a pituitary tumor and lost pituitary abilities: the headaches, the halved visual fields, increased thirst, urine, and a deep hunger for sleep.
Cushing—celebrated even then—offered him the most advanced treatment of the day, surgically relieving the man’s intracranial pressure and injecting him with ground whole pituitary gland. The patient rallied but couldn’t tolerate the injections. That prompted Cushing’s drastic step: he twice transplanted a fetal pituitary gland into the patient’s cortex, hoping it would take root.
Today, a century later, neurosurgeon Alfredo Quiñones-Hinojosa also carries out pituitary surgeries at Hopkins. His approach is often the endonasal and transsphenoidal one Cushing used, but “the procedure, overall, is a far cry from the old outcomes here,” he says, when 25 percent of patients died in pituitary surgery. Because pituitary tumors are so common—in perhaps 10 percent of the population—Quiñones- Hinojosa’s surgical skill and that of Hopkins colleagues is well-honed. They see some 100 patients a year in the OR. It’s that, along with MRI navigation, neuroendoscopy and other advances that has whittled the mortality figures.
Still, what Cushing tried to do with his implants has never left Quiñones- Hinojosa’s mind. “I began thinking about it when I was a resident,” he says. Having healthy implanted cells in the brain to replace its missing growth hormone, for example—especially in the setting of a patient’s own internal feedback loops and time tables—would clearly rule.
To that end, Quiñones- Hinojosa heads a team of neuroscientists and cell biologists to advance what looks increasingly possible. Their hope, unlike Cushing’s, lies in stem cells.
No one has isolated the “pituitary stem cell” that could, in theory, regenerate the whole gland or its chosen parts, though most say it probably exists. But the Hopkins team believes, meanwhile, there’s much to learn from a subgroup of “brain tumor stem cells” that they tease from the noncancerous pituitary adenomas that Quiñones-Hinojosa resects in the OR. Put in the right medium, he says, the cells differentiate to produce the various hormones.
Though “regenerative medicine” for pituitary illness is some time away, other benefits of studying the stem cell cultures may be closer. “There’s a potential to discover what lets the adenomas keep dividing,” he says. “Our immediate hope is to find a simple way to reregulate that abnormal growth.”
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