Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 mcg) ACTH test in subjects with preclinical adrenal autoimmunity

OBJECTIVE: The appearance of 21-hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb-positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low-dose (1 μg) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency. DESIGN AND PATIENTS: We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510.4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B,n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Δ) between peak and basal levels. RESULTS: DΔF was significantly higher in group A (314.5 ± 115.8 nmol/l) than in group B (151.7 ± 88.2 nmol/l) (P = 0.041). ΔDDHEA and Δ17OHP were also significantly higher in group A (17.0 ± 13.5 nmol/l and 6.1 ± 4.4 nmol/l, respectively) than in group B (0.69 ± 2.25 nmol/l and 1.9 ± 1.7 nmol/l, respectively) (P = 0.002 and P = 0.041). The difference in ΔA between the two groups did not reach statistical significance (group A 321.8 ± 272.0 pmol/l vs. group B 157.0 ± 154.0 pmol/l). ΔDHEA, Δ17OHP and ΔA tended to correlate positively with ΔF (P = 0.039, P = 0.039 and P = 0.044, respectively), but the correlations did not reach significance after correction of the P-value. CONCLUSIONS: Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal auto-immunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.