Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery

Katherine English, Warrick J. Inder, Zara Weedon, Goce Dimeski, Jane Sorbello, Anthony W. Russell, Emma L. Duncan, Ross Cuneo

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Objective: To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months. Design: Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250 μg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). Patients and Measurements: Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6 months. 46% had pre-operative adrenal insufficiency. Primary outcome: week 1 OMT compared to glucocorticoid requirement at 6 months. Secondary outcomes: the performance of ITT as a “definitive” test and all tests compared to glucocorticoid requirement at 6 months. Results: Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80%-85%. Conclusions: Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6 weeks post-operatively.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalClinical Endocrinology
Issue number1
Publication statusPublished - Jul 2017
Externally publishedYes


  • cortisol
  • glucocorticoid replacement
  • metyrapone
  • pituitary surgery

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