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

Clin Endocrinol (Oxf). 2017 Jul;87(1):35-43. doi: 10.1111/cen.13334. Epub 2017 Apr 19.

Abstract

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.

Keywords: cortisol; glucocorticoid replacement; metyrapone; pituitary surgery.

MeSH terms

  • Adrenal Insufficiency / surgery
  • Adult
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Metyrapone / administration & dosage
  • Metyrapone / pharmacology*
  • Middle Aged
  • Pituitary Gland / surgery*
  • Pituitary-Adrenal System / physiology*
  • Postoperative Period
  • Predictive Value of Tests
  • Prospective Studies
  • Recovery of Function / physiology*
  • Steroid 11-beta-Hydroxylase / antagonists & inhibitors
  • Time Factors

Substances

  • Glucocorticoids
  • Steroid 11-beta-Hydroxylase
  • Hydrocortisone
  • Metyrapone