Precise Radiation Therapy May Also Help Cushing’s Patients Control Cortisol Levels

A type of precision radiation therapy, called stereotactic radiosurgery (SRS), helped patients with Cushing’s disease (CD) control hypercortisolism. It may be a treatment alternative for those unable to undergo surgery or whose disease recurs after surgery, a retrospective analysis reported.

The study, “Stereotactic Radiosurgery for Cushing’s Disease: Results of an International, Multicenter Study,” appeared in The Journal of Clinical Endocrinology & Metabolism.

Currently, the first-line therapy for CD is surgery to the pituitary gland — located at the base of the brain, just behind the eyes —  that is considered the master regulator of the body’s hormones. Cushing’s is often caused by a pituitary gland tumor.

“However, approximately 10-35% of patients do not achieve endocrine remission after surgery and an additional proportion … recur over time,” Gautam Mehta, with the Department of Neurological Surgery at the University of Virginia Health System wrote.

Recent studies have suggested that stereotactic radiosurgery (SRS), a form of radiation therapy that delivers high dose radiation precisely to a tumor, especially those in the brain, is a potential alternative for CD to conventional radiotherapy and, possibly, traditional surgery. SRS is often referred to as “surgery” because one session of this radiation therapy produces a result similar to that of actual surgery.

To judge endocrine outcomes and SRS risks in CD patients, the researchers retrospectively analyzed results obtained at 10 medical centers participating in the International Gamma Knife Research Foundation (IGKRF).

A total of 327 patients received a single-session of SRS using gamma knife radiosurgery, of which 278  were available for follow-up analysis. Follow-up typically included biochemical tests and magnetic resonance imaging (MRI) performed at six-month intervals for the first two years and annually thereafter. Mean follow-up was 5.6 years.

The study’s primary goal was to assess how well SRS controlled hypercortisolism, as detected with a cortisol urine test. Cortisol is a hormone produced by the adrenal glands, and patients with CD usually have high cortisol levels in their urine.

Patients’ radiologic response and side effects of the radiation treatment were also recorded.

The analysis showed that 95 percent of patients achieved tumor control. After 10 years, 80 percent had an initial control of hypercortisolism. But the problem eventually recurred in 18 percent of these patients.

Using SRS, patients took a median of 14.5 months for their cortisol levels to return to normal. In contrast, studies showed that conventional radiotherapy for CD normalized cortisol levels after 18 to 42 months.

These findings suggest that SRS may result in shorter response times than conventional radiotherapy. Overall, after 10 years of follow-up, durable control of hypercortisolism was experienced by 64 percent of patients, and 68 percent of those who received SRS as first-line therapy.

New endocrine gland dysfunction after SRS was experienced by 25% of patients, and new nerve disorder (cranial neuropathy) occurred in 3% of them, and anyone undergoing SRS “should be carefully counselled as to this particular risk,” the researchers said.

Still, “SRS for CD is well-tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS,” they concluded.