title: Hypothalamus-pituitary dysfunction is common in patients with stable cirrhosis and abnormal low dose synacthen test.
abstract: BACKGROUND
  Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics.
  
  
  METHODS
  Prospective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal.
  
  
  RESULTS
  46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198 nmol/L; p=0.02). Using ROC curve basal cortisol <254 nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p=0.001) with good accuracy (sensitivity 67%, specificity 81%).
  
  
  CONCLUSIONS
  A delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and Institute of Liver and Digestive Health, University College London and Royal Free Hospital, London, UK; Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy. Electronic address: g_fede@tiscali.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fede
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Spadaro
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Privitera
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Tomaselli
authors.affiliation: Academic Department of Endocrinology, Royal Free Hospital, London, UK.
authors.forename: Pierre-Marc
authors.initials: PM
authors.lastname: Bouloux
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Purrello
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and Institute of Liver and Digestive Health, University College London and Royal Free Hospital, London, UK.
authors.forename: Andrew Kenneth
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003366:Cosyntropin / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D003366:Cosyntropin; D006854:Hydrocortisone
keywords: Adrenal insufficiency; Cirrhosis; Long synacthen test; Low dose short synacthen test