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


Jennifer M. Barker, Division of Pediatric Endocrinology, The Children’s Hospital, 13123 E. 16th Ave., B-265 Aurora, CO 80045, USA. Tel.: 720 777 8242; Fax: 720 777 7301; E-mail:


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.