A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome

J Clin Endocrinol Metab. 1993 Nov;77(5):1308-12. doi: 10.1210/jcem.77.5.8077325.


The objective of this study was to develop criteria for the interpretation of a morning ovine CRH stimulation test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Its design was retrospective review, and its setting was the in-patient unit of a tertiary care center. One hundred and eighteen patients with proven Cushing's disease or ectopic ACTH secretion were studied. The percent change in plasma ACTH and cortisol levels after CRH administration (1 microgram/kg BW) was calculated for each patient using 3 combinations of pre-CRH values (-15, -10, -5, and -1 min) and 6 combinations of post-CRH values (15, 30, 45, and 60 min). The diagnostic performance of these 36 sets of response measures was compared. The mean ACTH concentrations 15 and 30 min after CRH increased by at least 35% above the mean basal value at -5 and -1 min in 93 of 100 patients with Cushing's disease, but in none of the 16 patients with ectopic ACTH secretion. This measure gave the best sensitivity (93%) and specificity (100%). The best cortisol criterion was a mean increase at 30 and 45 min of 20% or more above mean basal values at -5 and -1 min, which gave a sensitivity of 91% and a specificity of 88%. We developed a simplified diagnostic test with 100% specificity using ACTH measurements 5 and 1 min before and 15 and 30 min after CRH administration. Although all patients with ectopic ACTH secretion had less than a 35% increase in ACTH, the probability of Cushing's disease was high at all levels of response, indicating that other tests should be performed to confirm the diagnosis.

MeSH terms

  • ACTH Syndrome, Ectopic / diagnosis
  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / physiology*
  • Animals
  • Circadian Rhythm
  • Corticotropin-Releasing Hormone*
  • Cushing Syndrome / diagnosis*
  • Diagnosis, Differential
  • Diagnostic Errors
  • Humans
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sheep
  • Time Factors


  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone