Endocrine Abstracts

Autoimmune Addison’s disease (AAD) occurs in approximately 1:8000 individuals. Its autoimmune pathogenesis is made evident by the presence of circulating 21-hydroxylase autoantibodies. A recent international program aimed at standardizing adrenal autoantibody measure to optimize both the etiological classification of the disease and the identification of at-risk subjects. Approximately 1% of subjects with autoimmune endocrine diseases and 5% of women with primary ovarian insufficiency are positive for 21OHAb, not necessarily in association with clinical symptoms of adrenal insufficiency. Detection of adrenal autoantibodies in subjects with no clinical signs of adrenal insufficiency defines the so-called subclinical AAD. The overall risk for future development of AAD in 21OHAb-positive individuals is as high as 40% at 10 years. The risk can be stratified on the basis of hormonal parameters, such as basal aldosterone, plasmatic renin activity, basal and ACTH-stimulated serum cortisol and basal plasma ACTH. A subnormal response to the Synacthen test and an increased plasma ACTH mark the irreversible phase of the disease, that evolves towards clinical AAD in over 90% of cases. On the other hand, only a minorityy of cases with normal ACTH levels and normal cortisol increase after the ACTH test progresses towards clinical AAD. Additional risk factors are male gender and high autoantibody titer, while available genetic markers are poor predictors of progression towards the clinical form of the disease. During the last years, studies have addressed the problem of the optimization of the Synacthen test, as the classical stimulation with 250 μg co-syntropin is largely supraphysiological. The low-dose test, performed with 1 μg of synthetic ACTH, is able to accurately discriminate subjects with subnormal cortisol response. An ongoing European study is testing the predictive value of a very low-dose test, performed using 0.5 μg of synthetic ACTH.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.