title: Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value.
abstract: BACKGROUND
  Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented.
  
  
  OBJECTIVE
  To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS.
  
  
  METHODS
  Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, 0400 and 0800 h) before treatment (Day 0) and 10 days, and 30 days and 1-2 years after the onset of trilostane therapy. The temporal pattern of insulin was analysed using a linear mixed model approach, and the prognostic value of measurements on Day 0 assessed using receiver-operating characteristic analysis.
  
  
  RESULTS
  Horses with ECS showed a diurnal pattern of serum insulin concentration, highest value at 1200 h, and this pattern was not altered by treatment with trilostane. Furthermore, despite a mild increase of serum insulin concentrations after 10 days of trilostane therapy, insulin concentration was unaffected in the long-term. Low serum insulin concentrations at the beginning of the trial were significantly associated with improved survival to 1-2 years. The 1200 h sampling before treatment had the highest prognostic value for prediction of survival with a sensitivity and specificity of at least 90% for serum insulin at < 62 and > 188 microu/ml to predict survival and nonsurvival, respectively.
  
  
  CONCLUSIONS
  Insulin is a useful prognostic indicator for ECS, but potentially large variations can occur throughout a 24 h period, indicating a single sample may not be representative. Serum insulin concentration did not increase over 1-2 years in horses receiving trilostane therapy.
authors.affiliation: Department of Veterinary Clinical Sciences, The Royal Veterinary College, Hawkshead Lane, Hatfield, Hertfordshire AL9 7TA, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: McGowan
authors.forename: R
authors.initials: R
authors.lastname: Frost
authors.forename: D U
authors.initials: DU
authors.lastname: Pfeiffer
authors.forename: R
authors.initials: R
authors.lastname: Neiger
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006734:Horse Diseases / Q000097:blood / Q000188:drug therapy*; D006736:Horses; D006854:Hydrocortisone / Q000037:antagonists & inhibitors* / Q000097:blood; D007328:Insulin / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D007328:Insulin; D013196:Dihydrotestosterone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane; D006854:Hydrocortisone