SFEBES2014 Oral Communications Clinical (6 abstracts)
Effectiveness of metyrapone in 195 patients with Cushing's syndrome
Eleni Daniel 1 , Simon Aylwin 2 , Omar Mustafa 2 , Steve Ball 3,4 , Atif Munir 4 , Kristien Boelaert 5 , Vasileios Chortis 5 , Daniel J Cuthbertson 6 , Christina Daousi 6 , Surya Rajeev 7 , Julian Davis 8 , Kelly Cheer 9 , William Drake 10 , Kirun Gunganah 10 , Ashley Grossman 11,13 , Mark Gurnell 12 , Andrew Powlson 12 , Niki Karavitaki 11,13 , Isabel Huquet 13 , Tara Kearney 14 , Kumar Mohit 14 , Karim Meeran 15 , Neil Hill 15 , Aled Rees 16 , Peter J Trainer 17 , Andrew J Lansdown 16 , Anna-Elisabeth H Minder 17 & John Newell-Price 1
1The Medical School, University of Sheffield, Sheffield, UK; 2King’s College Hospital NHS Foundation Trust, London, UK; 3The Medical School, Newcastle University, Newcastle, UK; 4Royal Victoria Infirmary, Newcastle, UK; 5College of Medical and Dental Sciences, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK; 6Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK; 7Aintree University Hospital, Liverpool, UK; 8Centre for Endocrinology and Diabetes, University of Manchester, Manchester, UK; 9Manchester Royal Infirmary, Manchester, UK; 10Department of Endocrinology, St Bartholomew’s Hospital, London, UK; 11University of Oxford, Oxford, UK; 12School of Clinical Medicine, University of Cambridge, Cambridge, UK; 13Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK; 14Salford Royal NHS Foundation Trust, Salford, UK; 15Imperial College, London, UK; 16School of Medicine, Cardiff University, Cardiff, UK; 17The Christie NHS Foundation Trust, Manchester, UK.
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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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