The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis

Clin Endocrinol (Oxf). 1994 May;40(5):603-9. doi: 10.1111/j.1365-2265.1994.tb03011.x.


Objective: The ACTH stimulation test examines adrenal responsiveness but may not examine the entire hypothalamic-pituitary-adrenal (HPA) axis and requires parenteral administration. The cortisol response to hypoglycaemia provides an index of activity of the entire HPA axis but is demanding for patients and medical staff. The aim of the present study was to examine the performance of the overnight single-dose metyrapone test as it provides a simple alternative test for HPA axis function.

Design: Audit of the overnight metyrapone test performed in one centre between 1979 and 1991.

Patients: Three hundred and ninety-eight patients underwent 576 tests. Comparisons between the responses to metyrapone and the ACTH stimulation test and of the responses to metyrapone and insulin induced hypoglycaemia test were possible in 87 and 17 patients respectively.

Measurements: Following the midnight administration of metyrapone tablets, 30 mg/kg orally, blood samples were obtained between 0800 and 0930 h for radioimmunoassay of both 11-deoxycortisol and cortisol.

Results: Five hundred and seventy-six metyrapone tests were performed on 398 patients with no serious side-effects encountered. Adrenal insufficiency was diagnosed in 105 patients. Of these, 18 had a primary adrenal disorder and 87 had a disorder of the hypothalamic-pituitary unit. One hundred per cent concordance between the metyrapone, the ACTH and the hypoglycaemia test was seen in patients with primary adrenal insufficiency. In 19 patients with secondary adrenal insufficiency, who underwent both the metyrapone and the ACTH tests, discord between these two tests was observed in 10 patients (53%). Nine of these patients demonstrated a normal response to ACTH and a subnormal response to metyrapone. In only one patient was an abnormal cortisol response to ACTH associated with a normal response to metyrapone. In contrast, in 17 patients discord between the metyrapone and the hypoglycaemia test was seen in only 1 patient who demonstrated a normal response to the metyrapone test and a subnormal response to hypoglycaemia.

Conclusion: Since the metyrapone test gives similar information about hypothalamic-pituitary axis function as does the hypoglycaemia test, we recommend the use of the overnight metyrapone test as a safe, simple and reliable index of the hypothalamic-pituitary axis integrity. The ACTH stimulation test should not be used for patients suspected of having secondary adrenal insufficiency.

Publication types

  • Comparative Study

MeSH terms

  • Adrenal Insufficiency / physiopathology
  • Adrenocorticotropic Hormone
  • Cortodoxone / blood
  • Humans
  • Hydrocortisone / blood
  • Hypoglycemia / physiopathology
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Medical Audit*
  • Metyrapone*
  • Pituitary-Adrenal System / physiopathology*


  • Adrenocorticotropic Hormone
  • Cortodoxone
  • Hydrocortisone
  • Metyrapone