Clinical Effectiveness of Metyrapone Monotherapy 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Research output: Contribution to conference (unpublished)Abstractpeer-review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. The few published reports on metyrapone use pertain to limited patient numbers. Method:A retrospective survey was conducted across 13 tertiary centres in England and Wales. 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. Eucortisolemia was defined according to the monitoring test used as a mean cortisol ‘day curve’ value ≤300nmol/l, a urinary free cortisol bellow the upper limit of normal (ULN) or a 9am serum cortisol <ULN (but <600nmol/l). Results: 195 patients received metyrapone (160 as monotherapy). Average age was 49.6 +/-15.7 years: 87.2% had metyrapone in conjunction with other interventions (surgery, radiotherapy or chemotherapy) while 12.8% had cortisol-lowering treatment alone. Dose-titration was used in 81% of patients, whereas 19% had a block-and-replace regimen. A total of 138 patients received metyrapone monotherapy for a mean duration of 162 days before any other intervention took place. The etiology of Cushing’s syndrome in this subgroup was: pituitary-dependent disease [CD, 59% (macroadenoma 32% of CD)], ectopic ACTH syndrome (EAS, 17%), adrenocortical carcinoma (ACC, 4%), adrenal adenoma (AA, 17%) and other benign adrenal disease (3%). Hypokalemia was actively managed with potassium levels increasing during metyrapone therapy (3.90mmol/L Vs 3.68mmol/L, p=0.0026). In this subgroup, 74% achieved eucortisolemia on varying doses: CD 1370mg, EAS 2080mg, AA 1170mg, ACC 750mg daily in divided doses. The preferred monitoring method was by cortisol ‘day-curves’, followed by 9am cortisol and urinary free cortisol. Overall, 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 eucortisolemia in over 70% of patients without any other cortisol-lowering intervention, 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
EventInternational Congress of Endocrinolgy / ENDO 2014 - Chicago, United States
Duration: 21 Jun 201424 Jun 2014

Conference

ConferenceInternational Congress of Endocrinolgy / ENDO 2014
CountryUnited States
CityChicago
Period21/06/1424/06/14