Metopirone effective treatment for hypercortisolemia in Cushing’s syndrome

Hypercortisolemia in Cushing’s syndrome can be controlled with Metopirone therapy, according to recent study findings published in The Journal of Clinical Endocrinology & Metabolism.

John Newell-Price, PhD, FRCP, of the University of Sheffield in the United Kingdom, and colleagues evaluated 195 patients with Cushing’s syndrome to determine the effect of Metopirone (metyrapone, HRA Pharma) on the control of excess cortisol. Cushing’s syndrome was most commonly Cushing’s disease (n = 115), followed by ectopic adrenocorticotropic hormone (ACTH; n = 37), benign adrenal disease (n = 30), adrenocortical carcinoma (n = 10), ACTH-independent macronodular adrenal hyperplasia (n = 2) and primary pigmented nodular adrenal hyperplasia (n = 1).

The biochemical parameters of activity of Cushing’s syndrome were measured by mean serum cortisol day-curve (target, 150-300 nmol/L), early morning serum cortisol and 24-hour urinary free cortisol.

Most participants received monotherapy (n = 164) and had significant improvements in excess cortisol during treatment. Significant improvements were revealed from first to last review for cortisol day-curve, early morning cortisol and 24-hour urinary free cortisol.

At last review, 55% of participants who had cortisol day-curve, 43% who had urinary free cortisol, 46% who had early morning cortisol less than 331 nmol/L and 76% who had early morning cortisol less than the upper limit of normal/600 nmol/L achieved control.

The median final dose of metyrapone was 1,375 mg among those with Cushing’s disease, 1,500 mg among those with ectopic ACTH, 750 mg among those with benign adrenal disease and 1,250 among those with adrenocortical carcinoma.

Twenty-five percent of participants experienced adverse events, with the most common being mild gastrointestinal upset and dizziness. Most of the adverse events occurred within 2 weeks of initiation or dose increase and were reversible.

“Overall more than 80% of patients showed an improvement in levels of circulating cortisol with over 50% achieving biochemical eucortisolemia when on monotherapy when assessed by the stringent criterion of control on a [cortisol day-curve],” the researchers wrote. “It is likely that additional therapies were added because of the severity of disease and clinician preference, but the retrospective and multicenter nature of our study precludes a formal assessment of this. Furthermore, our data support that metyrapone monotherapy is an effective treatment for hypercortisolemia either before or after surgical intervention to the primary cause of [Cushing’s syndrome].” – by Amber Cox

Disclosure: Newell-Price reports various financial ties with HRA Pharma and Novartis. Please see the full study for a list of all other authors’ relevant financial disclosures.


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