Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies

Clin Endocrinol (Oxf). 2012 May;76(5):617-24. doi: 10.1111/j.1365-2265.2011.04276.x.


Context: 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.

Design, setting and participants: 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.

Main outcome measured: 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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / blood*
  • Addison Disease / diagnosis*
  • Addison Disease / immunology
  • Adolescent
  • Adrenocorticotropic Hormone / blood
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Biomarkers / blood*
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / blood
  • Predictive Value of Tests
  • Prognosis
  • Renin / blood
  • Steroid 21-Hydroxylase / immunology
  • Time Factors
  • Young Adult


  • Autoantibodies
  • Biomarkers
  • Adrenocorticotropic Hormone
  • Steroid 21-Hydroxylase
  • Renin
  • Hydrocortisone