title: ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test.
abstract: OBJECTIVE
  The aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome.
  
  
  METHODS
  We retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B) after 8 mg of dexamethasone was evaluated as a supplementary criterion.
  
  
  RESULTS
  An increase in ACTH of ≥ 43%B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases.
  
  
  CONCLUSIONS
  The present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive.
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ritzel
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Berr
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Osswald
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Reisch
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schneider
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Honegger
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Geyer
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schopohl
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der Universität München, Ziemssenstraße 1, D-80336 Munich, GermanyDepartment of NeurosurgeryUniversity of Tuebingen, Tuebingen, GermanyInstitut für klinische RadiologieKlinikum der Ludwig-Maximilians-Universität München, Munich, Germany Martin.Reincke@med.uni-muenchen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D003480:Cushing Syndrome / Q000097:blood* / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000175:diagnosis*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone