title: Combined Administration of Ghrelin and Corticotropin-Releasing Hormone in the Diagnosis of Cushing's Disease.
abstract: OBJECTIVE
  Exaggerated adrenocorticotropic hormone (ACTH) and cortisol responses to ghrelin in Cushing's disease (CD) have previously been reported, similarly to responses to corticotropin-releasing hormone (CRH). We assessed the ability of ghrelin to enhance ACTH and cortisol responses when added to CRH stimulation in CD patients.
  
  
  METHODS
  In 21 CD patients (18 females, 3 males; age 49.8 ± 10.2 years; BMI 29.8 ± 0.8) and 8 healthy subjects (7 females, 1 male; age 40.6 ± 5.3 years; BMI 29.9 ± 1.2), we administered (1) ghrelin 100 µg i.v. bolus, (2) CRH 100 µg i.v. bolus, and (3) ghrelin + CRH combination. ACTH and cortisol were analyzed by commercially available kits from samples taken at 0, 15, 30, 45, 60, 90 and 120 min. ACTH and cortisol responses were calculated as peak and area under the curve (AUC0-120 min).
  
  
  RESULTS
  ACTH and cortisol at baseline and stimulated with ghrelin and/or CRH (peak and AUC0-120 min) were significantly higher in CD patients compared to controls (p < 0.01). ACTH and cortisol responses to ghrelin or CRH were similar in CD patients. Combined ghrelin + CRH administration in CD patients produced the highest ACTH response (peak and AUC0-120 min) compared to ghrelin or CRH alone (p < 0.01). Cortisol responses after ghrelin + CRH were uncoupled with ACTH responses and similar to the response to ghrelin or CRH alone in both groups. ACTH and cortisol responses, during all three tests, were similar in CD patients with micro- or macroadenomas.
  
  
  CONCLUSIONS
  Ghrelin administration causes exaggerated ACTH and cortisol responses in CD patients compared to healthy controls. In combination with CRH, it additionally enhances ACTH secretion without further additive effect on cortisol output.
authors.affiliation: Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Miljić
authors.forename: Snežana
authors.initials: S
authors.lastname: Polovina
authors.forename: Mirjana
authors.initials: M
authors.lastname: Doknić
authors.forename: Sandra
authors.initials: S
authors.lastname: Pekić
authors.forename: Marko
authors.initials: M
authors.lastname: Stojanović
authors.forename: Milan
authors.initials: M
authors.lastname: Petakov
authors.forename: Dragan
authors.initials: D
authors.lastname: Micić
authors.forename: Vera
authors.initials: V
authors.lastname: Popović
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D019540:Area Under Curve; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D054439:Ghrelin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone