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

Abstract

Objective

To determine if an overnight metyrapone test (OMT) within the first week post pituitary 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 day 3 and 4 post-operatively, OMT day 5-7 and week 6, 250μg short Synacthen test (SST) week 6 and insulin tolerance test (ITT) week 7.

Patients and Measurements

Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) and 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

OMT 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.

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