Human Corticotropin-Releasing Hormone Tests: 10 Years of Real-Life Experience in Pituitary and Adrenal Disease

J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa564. doi: 10.1210/clinem/dgaa564.


Context: The human corticotropin-releasing hormone (CRH) test (hCRHtest) is used to differentiate Cushing disease (CD) from ectopic adrenocorticotropin (ACTH) secretion (EAS), to assess autonomous cortisol secretion by the adrenal glands, and to characterize pseudo-Cushing syndrome (CS) or adrenal insufficiency (AI).

Main outcome measure: The main outcome measure of this study was to assess the diagnostic accuracy of the hCRHtest.

Methods: We measured ACTH and cortisol levels; collected the peak values (peakACTH and peakcortisol), and calculated the percentage increases (∆%ACTH and ∆%cortisol) after an intravenous bolus of 100 μg hCRH.

Design and setting: This cross-sectional study of hCRH tests from 2010 to 2019 took place in a referral university hospital center.

Patients: We enrolled 200 patients: 86 CD, 15 EAS, 18 adrenal CS, 25 mild adrenal autonomous cortisol secretion, 31 pseudo-CS, and 25 suspected AI.

Results: The hCRHtest was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions (P = .048). PeakACTH and peakcortisol were higher in CD, and ∆%ACTH and ∆%cortisol were able to differentiate CD from EAS with a sensitivity and specificity greater than 80%. In patients with low (< 10 pg/mL) or indeterminate (10-20 pg/mL) basalACTH levels, an absent or reduced peakACTH response was able to differentiate adrenal from ACTH-dependent forms. PeakACTH and peakcortisol after hCRHtest were lower in pseudo-CS than in CD, but ∆%ACTH and ∆%cortisol were similar. The role of hCRHtest in patients with AI was limited.

Conclusions: The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH.

Keywords: ACTH; Cushing disease; Cushing syndrome; adrenal adenoma; ectopic ACTH secretion.

MeSH terms

  • ACTH Syndrome, Ectopic / blood
  • ACTH Syndrome, Ectopic / diagnosis*
  • Adrenal Insufficiency / blood
  • Adrenal Insufficiency / diagnosis*
  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Corticotropin-Releasing Hormone*
  • Cross-Sectional Studies
  • Diagnosis, Differential
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / blood
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary Function Tests
  • Pituitary-Adrenal Function Tests
  • Sensitivity and Specificity


  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone