title: Potential role for retinoic acid in patients with Cushing's disease.
abstract: BACKGROUND
  Cushing's disease, i.e. cortisol excess due to an ACTH-secreting pituitary adenoma, is a rare disorder with considerable morbidity and mortality but no satisfactory medical treatment as yet. Experimental data have recently shown that retinoic acid restrains ACTH secretion by tumoral corticotropes.
  
  
  OBJECTIVE
  Our objective was to evaluate the efficacy and safety profile of retinoic acid treatment in patients with Cushing's disease.
  
  
  METHODS
  This is a prospective, multicenter study. Seven patients with Cushing's disease (three men, four postmenopausal women) were started on 10 mg retinoic acid daily and dosage increased up to 80 mg daily for 6-12 months. ACTH, urinary free cortisol (UFC), and serum cortisol as well as clinical features of hypercortisolism and possible side effects of retinoic acid were evaluated at baseline, during retinoic acid administration, and after drug withdrawal.
  
  
  RESULTS
  A marked decrease in UFC levels was observed in five patients; mean UFC levels on retinoic acid were 22-73% of baseline values and normalization in UFC was achieved in three patients. Plasma ACTH decreased in the first month of treatment and then returned to pretreatment levels in responsive patients whereas no clear-cut pattern could be detected for serum cortisol. Blood pressure, glycemia, and signs of hypercortisolism, e.g. body weight and facial plethora, were ameliorated to a variable extent on treatment. Patients reported only mild adverse effects, e.g. xerophthalmia and arthralgias.
  
  
  CONCLUSIONS
  Long-term treatment with retinoic acid proved beneficial and well tolerated in five of seven patients with Cushing's disease. This represents a novel, promising approach to medical treatment in Cushing's disease.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Istituto Auxologico Italiano, Piazzale Brescia 40, 20149 Milan, Italy. fpg@auxologico.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Pecori Giraldi
authors.forename: Alberto Giacinto
authors.initials: AG
authors.lastname: Ambrogio
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Andrioli
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguin
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karamouzis
authors.forename: Iannis
authors.initials: I
authors.lastname: Karamouzis
authors.forename: Salvatore Maria
authors.initials: SM
authors.lastname: Corsello
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontercorvi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone