Korlym as Good as Adrenal Surgery for Treating Ectopic Cushing’s Syndrome, Study Finds

Korlym (mifepristone) is effective for the treatment of ectopic Cushing’s syndrome patients, with survival rates comparable to patients who undergo bilateral adrenalectomy (removal of the adrenal glands), new research shows.

The study, “Mifepristone in the treatment of the ectopic adrenocorticotropic hormone syndrome,” was published in the journal Clinical Endocrinology.

Cushing’s syndrome is most commonly caused by a type of tumor known as a pituitary adenoma. These tumors produce too much of the adenocorticotropic hormone (ACTH), which acts on the adrenal glands to induce cortisol secretion.

In some cases, tumors located elsewhere in the body may also produce excess ACTH and cause Cushing’s syndrome. In this case, patients have a form of the disease called ectopic Cushing’s syndrome.

Ectopic disease commonly results from benign and malignant tumors located in the lungs, pancreas, and brain.

While the first-line treatment for all forms of Cushing’s syndrome is surgical removal of the tumor, this can be difficult in ectopic Cushing’s syndrome patients, as it is more challenging to determine the location of the tumor.

In difficult cases, physicians can perform a bilateral adrenalectomy to remove the source of cortisol. However, this approach makes patients dependent on glucocorticoid replacement therapies for the rest of their lives.

Because of this, physicians often turn toward pharmacological therapy to control high cortisol levels.

In fact, pharmacological therapy can preoperatively be used in patients to either achieve immediate control of hypercortisolism, for patients that are not good surgical candidates, or when the source of Cushing’s syndrome is hard to determine.

Korlym is approved in the U.S. for patients with high blood sugar caused by excess cortisol in Cushing’s syndrome patients who have failed or are not candidates for surgical cure.

But while studies have shown it improves clinical and metabolic parameters in Cushing’s disease (caused by pituitary tumors) no studies have investigated the effects of Korlym in ectopic Cushing’s syndrome patients.

So researchers examined data from all ectopic Cushing’s patients treated at the University of Michigan from 1997 to 2017. Among the 55 patients included, 16 had been treated with Korlym.

Out of these 16, eight had neuroendocrine tumors (tumors that arise from the endocrine and nervous system) and two had carcinomas (cancer that starts in cells that make up the skin or the tissue lining organs). In the remaining six patients, researchers were unable to locate their tumors.

Treatment with Korlym was most commonly administered if the patient exhibited psychosis, uncontrolled glucose, or hypertension (high blood pressure). The median maintenance dose was 600 mg/day.

Results showed that symptoms of psychosis improved within 48 hours in all three patients who exhibited psychosis.

Additionally, among the 16 patients who exhibited uncontrolled glucose levels, 14 improved with Korlym.

Of note, the overall survival at 24 months was equivalent between patients treated with Korlym and patients who received a bilateral adrenalectomy.

“Mifepristone [Korlym] is effective in treating EAS [ectopic Cushing’s syndrome] for over two years, and survival was not different from that of patients treated with bilateral adrenalectomy,” investigators wrote.

However, 31 percent of patients had worsening low potassium levels and increased blood pressure, suggesting that patients on Korlym may require concomitant treatment for those side effects.