Metyrapone Reduced Urinary-Free Cortisol Levels in Cushing Syndrome

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The most frequently reported adverse events were nausea and upper abdominal pain, dizziness, and myalgia.
The most frequently reported adverse events were nausea and upper abdominal pain, dizziness, and myalgia.

Metyrapone treatments helped patients with Cushing syndrome reach normal, urinary-free cortisol levels in the short-term and also had long-term benefits, according to a study published in Endocrine.

This observational, longitudinal study evaluated the effects of the 11β -hydroxylase inhibitor metyrapone on adult patients with Cushing syndrome. Urinary-free cortisol and late-night salivary cortisol levels were evaluated in 31 patients who were already treated with metyrapone to monitor cortisol normalization and rhythm.

The average length of metyrapone treatment was 9 months, and 6 patients had 24 months of treatment. After 1 month of treatment, the mean urinary-free cortisol was reduced from baseline by 67% and mean late-night salivary cortisol level decreased by 57%. 

Analyzing only patients with severe hypercortisolism, after 1 month of treatment, the mean urinary-free cortisol decreased by 86% and the mean late-night salivary cortisol level decreased 80%. After 3 months, normalization of the mean urinary-free cortisol was established in 68% of patients. Mean late-night salivary cortisol levels took longer to decrease, especially in severe and very severe hypercortisolism, which could take 6 months to drop. Treatment was more successful at normalizing cortisol excretion (70%) than cortisol rhythm (37%). Nausea, abdominal pain, and dizziness were the most common adverse events, but no severe adverse event was reported.

Future research is needed to evaluate a larger cohort with randomized dosages and stricter inclusion criteria to evaluate metyrapone's effects on cortisol further.

Study researchers conclude that metyrapone was successful and safe in lowering urinary-free cortisol after just 1 month of treatment and controlling long-term levels in patients with Cushing syndrome.

This study was supported by Novartis.

Reference

Ceccato F, Zilio M, Barbot M, et al. Metyrapone treatment in Cushing's syndrome: a real-life study [published online July 16, 2018]. Endocrine. doi: 10.1007/s12020-018-1675-4

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