LEVELS OF ADRENOCORTICAL AUTOANTIBODIES CORRELATE WITH THE DEGREE OF ADRENAL DYSFUNCTION IN SUBJECTS WITH PRECLINICAL ADDISONS-DISEASE

To test the hypothesis that levels of adrenal autoantibodies correlate with the degree of adrenal dysfunction, we followed up adrenal cortex autoantibody (ACA) titers and 21-hydroxylase (21OH) autoantibody (21O HAb) levels in 19 ACA-positive subjects with preclinical Addison's dis ease. On enrollment, all the 19 ACA-positive subjects were positive fo r 21OHAb. At follow-up, the concordance rate for simultaneous presence /absence of both ACA and 21OHAb was as high as 91% and a strong, posit ive correlation between 21OHAb levels and ACA titers was observed (P < 0.0001). The levels of adrenal autoantibodies were positively associa ted with the severity of adrenal dysfunction (ANOVA, P < 0.0001 for bo th 21OHAb and ACA): the 21OH index was significantly lower at stage 0 or 1 than as stage 2+3 (corrected P < 0.001 and P < 0.05) or stage 4 ( corrected P < 0.001 and < 0.01)Similarly, ACA titer at stage 4 was sig nificantly higher than stage 0(P < 0.001), stage 1(P < 0.001), and sta ge 2+3(P < 0.05); and ACA titer at stage 2+3 was higher than stage 0 ( P < 0.001) and stage 1 (P < 0.05). Iii subjects with progression of ad renal dysfunction (n = 14), levels of 21OHAb and ACA increased signifi cantly (P = 0.041 and P = 0.002) during the follow-up period. In 5 sub jects, the remission of biochemical signs of adrenal dysfunction was a ssociated with the disappearance of both ACA and 21OHAb. Our study sho ws that the levels of adrenal autoantibodies correlate with the degree of adrenal dysfunction, and this suggests that production of high-lev el 21OHAb strongly signals the destructive phase of the autoimmune dis ease process.