ADRENAL-CORTEX AND STEROID 21-HYDROXYLASE AUTOANTIBODIES IN ADULT PATIENTS WITH ORGAN-SPECIFIC AUTOIMMUNE-DISEASES - MARKERS OF LOW PROGRESSION TO CLINICAL ADDISONS-DISEASE .1.

Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without o vert hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, wi th the highest prevalence in those with premature ovarian failure (8.9 %). Forty-eight ACA-positive and 20 ACA-negative individuals were enro lled into a prospective study. Antibodies to steroid 21-hydroxylase (2 1-OH), steroid 17 alpha-hydroxylase (17 alpha-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitat ion assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enroll ment, 75% of ACA-positive patients had a normal adrenal function, whil e 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were pos itive in 91% of ACA-positive sera. Eleven patients were positive for s teroid-cell antibodies by immunofluorescence, and 9 revealed a positiv ity for antibodies to 17 alpha-OH and/or P450scc. During the prospecti ve study, overt Addison's disease developed in 21% and subclinical hyp oadrenalism in 29% of ACA-positive patients, while 50% maintained norm al adrenal function. Progression to Addison's disease was more frequen t in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 s tatus. All 20 persistently ACA-negative patients were also negative fo r antibodies to 21-OH, 17 alpha-OH, and P450scc, and all maintained no rmal adrenal function during follow-up. In conclusion, the detection o f ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison's disease.