Effectiveness of metyrapone in 195 patients with Cushing's syndrome

Research output: Contribution to conference (unpublished)Abstractpeer-review

Colleges, School and Institutes

Abstract

Background: Metyrapone is widely used in the UK for the control of cortisol excess in Cushing’s syndrome, but its use is not standardised. There are a few reports published on metyrapone use, mostly containing small patient numbers. Method: A retrospective survey was conducted across 13 tertiary centres. Using a standardised proforma, extensive data including monitoring and safety information were collected for patients with Cushing’s syndrome on metyrapone therapy between 1997 and 2013. Results: 195 patients received metyrapone (160 on monotherapy). Average age was 49.6±15.7 years. Aetiology of Cushing’s syndrome: pituitary-dependent disease (CD, 59% (macroadenoma 32% of CD)), ectopic ACTH syndrome (EAS, 18.9%), adrenocortical carcinoma (ACC, 14.9%) and adrenal adenoma (AA, 7.1%): 73.3% received metyrapone prior to surgery and 12.8% had cortisol-lowering therapy alone. Dose-titration was used in 81% of patients, whereas 19% had block-and-replace. The average starting dose was 1055 mg; median doses were 750 mg for CD and AA, 1000 mg for EAS, and 1500 mg for ACC. The preferred monitoring method was by cortisol day-curves, followed by 0900 h cortisol and urinary free cortisol. Hypokalaemia on therapy was actively managed, with potassium levels increasing during treatment (3.95 vs 3.66 mmol/l, P<0.0001). The mean treatment duration was 8 months, 81.4% achieving eucortisolaemia on varying doses: CD 1390 mg, EAS 1900 mg, AA 1080 mg, and ACC 1500 mg. 25.3% of patients developed side effects; most commonly gastrointestinal upset and hypoadrenalism. 88% of adverse events were managed as outpatients; 36% of patients treated for more than one month had ≤2 monitoring assessments and insufficient dose titration. Conclusion: This is the largest report of metyrapone use. Metyrapone was effective in achieving eucortisolaemia in over 80% of patients, with a satisfactory safety profile. A variety of monitoring regimens were used, but greater standardisation of practice and more active dose titration is needed.

Details

Original languageEnglish
Publication statusPublished - 2014
EventSociety for Endocrinology (BES 2014) - Liverpool, United Kingdom
Duration: 24 Mar 201427 Mar 2014

Conference

ConferenceSociety for Endocrinology (BES 2014)
CountryUnited Kingdom
CityLiverpool
Period24/03/1427/03/14