Targeted radiation therapy offers hope for tough Cushing’s cases
Study finds technique controls tumors, normalizes cortisol
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Stereotactic radiosurgery (SRS), a targeted form of radiation that precisely delivers high doses to tumors while sparing surrounding tissue, may be a safe and effective treatment to control hard-to-treat Cushing’s disease, according to a meta-analysis of published studies.
SRS induced biochemical remission in about two-thirds of cases and controlled tumor growth in more than 95% of patients whose disease had returned or failed to respond to prior treatments, the study found. Hypopituitarism (decreased function of the pituitary gland) was the most common side effect, occurring in nearly 30% of patients over time.
“Based on the available literature, SRS emerges as a safe and effective treatment, and its implementation in common clinical practice may play a relevant role in the management of [Cushing’s disease],” the researchers wrote.
The study, “Radiosurgery in recurrent and persistent Cushing’s Disease: a Systematic Review and Meta-Analysis,” was published in Neurosurgical Review.
Cushing’s disease is caused by pituitary gland tumors that trigger excess production of adrenocorticotropic hormone (ACTH). ACTH signals the adrenal glands, which sit atop the kidneys, to release cortisol, leading to the wide range of Cushing’s symptoms. Endoscopic transsphenoidal surgery, a minimally invasive procedure to remove the tumor through the nose, is considered the first-line treatment. However, 10% to 35% of patients do not achieve remission after their initial surgery.
Adapting pituitary tumor treatment to Cushing’s
Managing disease that persists or returns after surgery remains challenging. Medications often provide only partial control of cortisol levels, repeat surgery carries a higher risk of complications, and questions remain about the long-term safety of conventional radiation therapy. These challenges are especially concerning because many patients already face serious health complications from prolonged exposure to high cortisol levels.
SRS has been used for decades to treat pituitary tumors. But evidence specifically in people with recurrent or persistent Cushing’s disease has been limited.
To address this gap, researchers in Italy conducted a systematic review of studies published through May 2025 across three databases.
Persistent Cushing’s disease was defined as continued high cortisol levels six months after surgery, while recurrent disease referred to the return of high cortisol levels after an initial period of normalization following surgical treatment.
Of nearly 700 screened reports, nine studies met the inclusion criteria, covering 341 patients treated with SRS.
Nearly all patients (98.8%) had Cushing’s disease that persisted or returned after pituitary surgery. SRS was typically performed about 25.6 months (a little over two years) after a patient’s most recent surgery, and patients had a mean age of 40.6 at the time of treatment. In most cases, they received SRS in a single, high-dose session.
Patients were followed for a mean of 61.5 months (about five years) after treatment. Across the studies, SRS was highly effective at controlling tumor growth.
Scans showed that tumors remained stable or shrank in 97.4% of patients, indicating excellent long-term tumor control.
Cortisol normalization was achieved in 67.1% of patients, typically within about 26 months (a little over two years) after treatment.
Among 135 patients with available follow-up data, 21% experienced a later recurrence of high cortisol levels after initially achieving remission. Recurrence occurred on average 39 months (just over three years) after radiosurgery.
The most common long-term complication was new-onset hypopituitarism, which developed in about 28% of patients over time.
More serious complications were rare. Vision problems and cranial nerve damage each occurred in fewer than 2% of patients. No cases of brain tissue damage or injury to the carotid arteries (the major blood vessels that supply blood to the brain) were reported.
While hormone deficiencies remain a concern, “SRS is a potentially safer, yet more aggressive, treatment that allows for higher rates of control of recurrent [Cushing’s disease],” the researchers wrote.
Future studies are, however, needed to “properly assess SRS efficacy and safety in treating persistent and recurrent CD,” they concluded.
