Metyrapone Appears Effective in Cushing's Syndrome in Long Term

By Anne Harding

October 01, 2015

NEW YORK (Reuters Health) - The steroidogenesis inhibitor metyrapone appears to be an effective short- and long-term treatment for Cushing's syndrome (CS), according to a new retrospective multicenter study.

"Active dose titration is needed with careful biochemical and clinical monitoring," Dr. John Newell-Price of the University of Sheffield in the U.K. told Reuters Health by email. The findings were published online September 9 in the Journal of Clinical Endocrinology & Metabolism.

Metyrapone is widely used in the U.K. to treat hypercortisolism in CS patients, but is less widely used in the U.S., Dr. Newell-Price said. "Large prospective studies have not been done as the drug has been used since the 1950s, and known to be effective," he added.

The largest study of metyrapone for CS to date was in 91 patients, and published in 1991.

To investigate the drug in a contemporary series of patients, Dr. Newell-Price and his colleagues looked at 195 CS patients treated at 13 university hospitals. Some were on metyrapone monotherapy, while others received the drug with other cortisol-lowering medications.

More than 80% of patients overall showed a reduction in circulating cortisol when treated with metyrapone, while over half reached eucortisolemia.

Data from 38 patients receiving metyrapone for more than six months (mean, 18.6 months) showed that biochemical tests improved during treatment, with eucortisolemia achieved in 72% of patients with serum cortisol day-curves.

Hypokalemia is a potential complication of treatment with the study drug, Dr. Newell-Price and his team note.

"Our data suggest clinicians using metyrapone are well aware of the importance of monitoring and managing potassium levels since we found that these increase significantly with supportive measures during treatment," they write. "It is important to stress, however, that such active monitoring is required, as hypokalemia is also a potentially harmful feature of CS."

Adverse effects of metyrapone in the study included mild gastrointestinal symptoms and hypoadrenalism, but hirsutism was not reported.

Currently, Dr. Newell-Price and colleagues note, there is no standardized monitoring and dosing regimen for CS patients on metyrapone.

"We are planning to harmonise use in the U.K. to encourage better titration and monitoring to improve biochemical control and enhance patient benefit," Dr. Newell-Price said. "Metyrapone should be used by experts familiar with its mode of action, potential side effects and need for careful monitoring."

The study was supported by HRA Pharma.


J Clin Endocrinol Metab 2015.