Assessment of ACTH-sufficiency after pituitary surgery is complicated, with a profusion of tests and disagreement about which is ‘best’.  We performed a prospective study to compare the overnight metyrapone test performed at day 5 and week 6 post pituitary surgery, the short synacthen test (SST) at week 6 and the insulin tolerance test (ITT) at week 7 in the evaluation of post hypophysectomy ACTH sufficiency.  23 patients were enrolled between 2009 and 2011. Patients with Cushings Disease were excluded.  Standardised glucocorticoid replacement was given peri operatively. Glucocorticoid replacement was ceased if day 3 and 4 cortisol were >400nmol/L and the metyrapone test was normal (serum 11-deoxycortisol >200nmol/L by HPLC) at day 6, otherwise 20mg hydrocortisone/day was continued.   Short synacthen, overnight metyrapone and insulin tolerance tests  were performed in all patients at 6-7 weeks unless contraindicated.

No adverse events were experienced.  17 patients had ITT performed.  1 patient had insufficient stimulus on day 5 metyrapone test and 1 failed to attend for week 6 metyrapone test. Overall 7 patients had sufficient ACTH and 4 had insufficient ACTH on all tests and 5 had discordant data.  Mean stimulated ACTH (87.6ng/L and 134ng/L) and 11-deoxycortisol (284nmol/Land 460nmol/L) appeared lower at day 5 compared to week 6 data.  There were fewer false positives in the day 5 than 6 week test, when compared with the ITT peak cortisol 500nmol/L as gold standard.  The average 9hr post metyrapone cortisol values were similar (82nmol/L and 90.6nmol/L for day 5 and week 6 test respectively).  Overall the sensitivity and specificity (for ACTH sufficiency) were 87.5% and 86% respectively for the day 5 metyrapone test and 100% and 43% respectively for the week 6 metyrapone test compared with ITT as gold standard . The sensitivity and specificity for the SST were 100% and 71% respectively compared with the ITT as gold standard and 86% and 100% respectively compared with the 6 week metyrapone test as gold standard.  Day 3 or 4 cortisol >400nmol/L had a positive predictive value of 70% and 100% compared with ITT and 6 week metyrapone test respectively.

We conclude that: a) the Metyrapone test appears safe, b) peri operative HPA suppression may influence early but not late Metyrapone tests, and c) further data are required to establish which test provides the best combination of ease of administration, safety, cost and performance.