Benefits of Medication Before Surgery for Cushing’s Syndrome Still Unclear, Research Finds

In Europe, nearly 20 percent of patients with Cushing’s syndrome receive some sort of medication for the disease before undergoing surgery, a new study shows.

Six months after surgery, these patients had remission and mortality rates similar to those who received surgery as a first-line treatment, despite having worse disease manifestations when the study began. However, preoperative medication may limit doctors’ ability to determine the immediate success of surgery, researchers said.

A randomized clinical trial is needed to conclusively address if preoperative medication is a good option for Cushing’s patients waiting for surgery, they stated.

The study, “Preoperative medical treatment in Cushing’s syndrome. Frequency of use and its impact on postoperative assessment. Data from ERCUSYN,” was published in the European Journal of Endocrinology. 

Surgery usually is the first-line treatment in patients with Cushing’s syndrome. But patients also may receive preoperative medication to improve cortisol excess and correct severe diseases occurring simultaneously with Cushing’s.

Multiple studies have hypothesized that preoperative medication can have a beneficial effect on patients who undergo surgery. However, data on the beneficial impact of medication on morbidity, and the immediate surgical and long-term outcomes in patients with Cushng’s syndrome, are limited and inconclusive.

So, researchers made use of the European Registry on Cushing’s Syndrome (ERCUSYN), the largest database that collects information on diagnosis, management, and long-term follow-up in Cushing’s patients.

The team set out to collect information of the prevalence of preoperative medication in Cushing’s patients throughout Europe, and whether it influences patients’ outcomes after surgery. It also aimed to determine the differences between patients who receive preoperative medication versus those who undergo surgery directly.

Researchers analyzed 1,143 patients in the ERCUSYN database from 57 centers in 26 countries. Depending on what was causing the disease, patients were included in four major groups: pituitary-dependent Cushing’s syndrome (68%), adrenal-dependent Cushing’s syndrome (25%), Cushing’s syndrome from an ectopic source (5%), and Cushing’s syndrome from other causes (1%).

Overall, 20 percent of patients received medication – ketoconazole, metyrapone, or a combination of both – before surgery. Patients with ectopic and pituitary disease were more likely to receive medication compared to patients whose disease stemmed from the adrenal glands. Preoperative treatment lasted for a median of 109 days.

Patients in the pituitary group who were prescribed preoperative medication had more severe clinical features at diagnosis and poorer quality of life compared to those who received surgery as first-line treatment. No differences were found in the other groups.

But patients with pituitary-dependent disease receiving medication were more likely to have normal cortisol within seven days of surgery, or the immediate postoperative period, compared to patients who had surgery without prior medication. These patients also had a lower remission rate.

Within six months of surgery, however, there were no differences in morbidity or remission rates observed between each group. Also, no differences were seen in perioperative mortality rates – within one month of surgery.

Interestingly, researchers noted that patients who took medication prior to surgery were less likely to be in remission immediately after surgery. The reason, they suggest, might be because the medication already had begun to improve the clinical and biochemical signs of the disease, “so changes that take place in the first week after surgery may be less dramatic.”

“A randomized trial assessing simple endpoints, such as length of hospital stay, surgical impression and adverse effects of surgery, is needed to conclusively demonstrate that [preoperative medication] is a valid option in patients waiting for surgical correction of hypercortisolism,” the team concluded.