title: Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests.
abstract: OBJECTIVE
  To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS).
  
  
  METHODS
  In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone-CRH (Dex-CRH) test was performed in 54 patients.
  
  
  RESULTS
  FIFTY-THREE PATIENTS WERE DIAGNOSED WITH CD AND SUBSEQUENTLY TREATED. TWENTY PATIENTS WERE CLASSIFIED AS HAVING PSC. SERUM CORTISOL CIRCADIAN RHYTHM: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of >0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration >243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level >9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex-CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level >87 nmol/l (T=15 min) resulted in a PPV of 100% and an NPV of 90%.
  
  
  CONCLUSIONS
  The Dex-CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.
authors.affiliation: Division of Endocrinology, Room H555, Department of Internal Medicine, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Alwani
authors.forename: L W
authors.initials: LW
authors.lastname: Schmit Jongbloed
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000150:complications / Q000175:diagnosis*; D000236:Adenoma / Q000150:complications / Q000175:diagnosis*; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000378:metabolism; D003907:Dexamethasone; D003937:Diagnosis, Differential; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D011446:Prospective Studies; D012463:Saliva / Q000737:chemistry; D012680:Sensitivity and Specificity
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone