title: Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies.
abstract: BACKGROUND
  Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality.
  
  
  OBJECTIVE
  To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals.
  
  
  METHODS
  Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors.
  
  
  METHODS
  Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up.
  
  
  RESULTS
  Compared with nonprogressors, in the time period 2 months-2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11-22 pM, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3).
  
  
  CONCLUSIONS
  Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months-2 years preceding the onset of AD.
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors: Peter R
authors: PR
authors: Baker
authors: Priyaanka
authors: P
authors: Nanduri
authors: Peter A
authors: PA
authors: Gottlieb
authors: Liping
authors: L
authors: Yu
authors: Georgeanna J
authors: GJ
authors: Klingensmith
authors: George S
authors: GS
authors: Eisenbarth
authors: Jennifer M
authors: JM
authors: Barker
mesh_terms: D000224:Addison Disease / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012083:Renin / Q000097:blood; D013255:Steroid 21-Hydroxylase / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D012083:Renin; D006854:Hydrocortisone