The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery

Clin Endocrinol (Oxf). 2000 Sep;53(3):309-12. doi: 10.1046/j.1365-2265.2000.01093.x.


Objective: To compare the insulin hypoglycaemia test with the short overnight metyrapone test in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis posthypophysectomy.

Design: Prospective comparative study of the insulin hypoglycaemia test and the overnight metyrapone test in 32 patients 4-6 weeks after pituitary surgery.

Subjects: Thirty-two patients with known pituitary disease. None with present or previous Cushing's syndrome.

Outcome measurements: Maximum serum cortisol achieved during insulin induced hypoglycaemia compared with 0900 hours serum 11-deoxycortisol level following a weight related oral dose of metyrapone at 0000 h.

Results: One of the 32 patients required further surgery and was studied twice after each operation. Thirty-three results are therefore compared. Twenty-six of these had a normal cortisol response of 550 nmol/l or above leading to the cessation of replacement hydrocortisone. Six of these 26 patients however, failed the metyrapone test (11-deoxycortisol level less than 200 nmol/l). After 3-40 months (median 20 months) of follow-up off steroid therapy, no patient to date has displayed any clinical evidence of steroid deficiency. Of the seven patients who failed the insulin hypoglycaemia test, six also failed the metyrapone test.

Conclusions: The overnight metyrapone test identified more patients with possible ACTH deficiency than the insulin hypoglycaemia test. Further follow-up of these patients is required before a final judgement can be made as to whether more subtle but clinically relevant ACTH deficiency can be detected by the metyrapone test. Our clinical follow-up to date would not support this.

Publication types

  • Comparative Study

MeSH terms

  • Adenoma / physiopathology
  • Adenoma / surgery
  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Aged
  • Cortodoxone / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / blood*
  • Hypoglycemic Agents*
  • Hypophysectomy*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Insulin*
  • Male
  • Metyrapone*
  • Middle Aged
  • Pituitary Neoplasms / physiopathology
  • Pituitary Neoplasms / surgery
  • Pituitary-Adrenal System / physiopathology
  • Postoperative Period
  • Predictive Value of Tests
  • Prospective Studies


  • Hypoglycemic Agents
  • Insulin
  • Adrenocorticotropic Hormone
  • Cortodoxone
  • Hydrocortisone
  • Metyrapone