Metyrapone Rapidly Reduces Cortisol Levels in Cushing’s Syndrome Patients, Real-Life Study Shows

Treatment with metyrapone rapidly reduces cortisol levels in Cushing’s syndrome patients and keeps them low over the long term, a real-life study shows.

The study, “Metyrapone treatment in Cushing’s syndrome: a real-life study,” was published in the journal Endocrine.

Cushing’s syndrome is a condition where patients have too much cortisol in their blood, either because of a tumor or due to medication.

Controlling high cortisol levels is of great importance in these patients, even in those who may receive other therapeutic interventions — such as tumor removal.

Metyrapone, sold under the brand name Metopirone, is a potent inhibitor of the 11-beta-hydroxylase enzyme, which plays a key role in cortisol synthesis. This therapy is fast-acting, leading to a reduction in cortisol levels just 30 minutes after a single dose.

However, few retrospective studies have looked at how effective this medicine is in reducing the cortisol levels in Cushing’s syndrome patients.

To answer this question, as well as to investigate how metyrapone impacts late-night salivary cortisol production — a measure of cortisol daily variations — researchers conducted an observational study in 31 patients with a median age of 49 years.

Among the participants, 20 had Cushing’s disease — a form of Cushing’s syndrome caused by a tumor in the pituitary gland — five had a tumor in the adrenal glands — called adrenal Cushing’s syndrome — and six had a tumor elsewhere in the body — a Cushing’s syndrome subtype called ectopic ACTH syndrome.

Patients received treatment with metyrapone, either before or after surgery, for a median period of nine months. The dose was adjusted according to a patient’s cortisol levels.

Participants provided samples of urine and late-night saliva to measure their cortisol levels at the beginning of the study, and thereafter at regular time periods — one, three, six, 12, and 24 months.

The medicine led to a rapid decrease in cortisol levels, with patients experiencing a 67% median decrease in urinary cortisol levels and a 57% reduction in late-night salivary cortisol just one month after starting the therapy.

After three months, 68% of patients had their levels normalized and continued to have normal cortisol at 24 months.

For patients with very high cortisol levels, three to six months of treatment were needed to control hormone levels.  Nonetheless, these patients already showed an 86% reduction in urinary cortisol levels after the first month.

Two years after starting metyrapone treatment, 70% of the patients had normal cortisol levels in urine. But only 37% had the same outcome for salivary cortisol.

After normalizing cortisol levels, the patients dropped a median of 4 kg in body weight, and most of the diabetic patients were able to reduce the dose or number of anti-diabetic medications. No severe side effects were reported.

Based on these results, the researchers concluded that metyrapone is a “rapid-onset, long-term effective, and safe medical treatment” for Cushing’s syndrome patients.