Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency

Neth J Med. 2005 Dec;63(11):435-43.


Background: The short Synacthen test, the overnight metyrapone test and the insulin tolerance test are frequently used in the evaluation of patients suspected of adrenal insufficiency. in the present study, we established reference values for these diagnostic tests, as well as for baseline morning plasma cortisol and adrenocorticotrophic hormone (ACTH).

Methods: We studied 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. A short ACTH stimulation test (250 microg Synacthen iv), an overnight metyrapone test (2.0, 2.5, or 3.0 g given orally depending on body weight at 23.30 hours) and an insulin tolerance test (0.15 U/kg actrapid iv) were performed. Reference intervals are given as the means +/- 2SD of observed hormone concentrations after logarithmic transformation.

Results: The following reference values were established: 09.00 hr plasma cortisol 150 to 802 nmol/l, 09.00 hr plasma ACTH 8 to 93 ng/l, peak plasma cortisol after Synacthen 591 to 1,113 nmol/l, peak plasma cortisol after insulin-induced hypoglycaemia 557 to 1,015 nmol/l, and plasma 11-deoxycortisol after metyrapone 197 to 759 nmol/l.

Conclusion: We established reference values for diagnostic tests that are useful in the evaluation of patients suspected of primary or secondary/tertiary adrenal insufficiency.

MeSH terms

  • Adrenal Cortex Function Tests / methods*
  • Adrenal Cortex Function Tests / standards
  • Adrenal Insufficiency / blood*
  • Adrenal Insufficiency / diagnosis
  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / blood*
  • Biomarkers / blood
  • Cortodoxone / blood
  • Enzyme Inhibitors
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Hypoglycemic Agents
  • Insulin
  • Male
  • Metyrapone
  • Middle Aged


  • Anti-Inflammatory Agents
  • Biomarkers
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Adrenocorticotropic Hormone
  • Cortodoxone
  • Hydrocortisone
  • Metyrapone