ADRENAL AUTOANTIBODIES AND ORGAN-SPECIFIC AUTOIMMUNITY IN PATIENTS WITH ADDISONS-DISEASE

OBJECTIVE Autoimmune destruction of the adrenal gland is the major cau se of idiopathic Addison's disease, but the significance of 21-hydroxy lase autoantibodies and their correlation with the presence of other a utoantibodies have not so far been investigated in a larger population of patients with Addison's disease. We have now characterized a cohor t of patients with idiopathic Addison's disease (n = 97) regarding the specificity of autoantibodies against the adrenal cortex and, as Addi son's disease can be either an isolated condition or part of a polyend ocrine disorder, we investigated the presence of organ-specific polyen docrine autoimmunity in this patient population. DESIGN Cross-sectiona l study. MEASUREMENTS Autoantibodies were analysed with indirect immun ofluoresence (IF) on tissue preparations, ELISA and in Western blots u sing bacterially expressed proteins. RESULTS Eighty-four per cent (81/ 97) of the patient sera recognized the steroid-producing cells of the adrenal cortex in indirect IF. The antigen was identified sis 21-hydro xylase by 72% (70/97) of the patient sera in Western blots. Seven sera that were negative on adrenocortical IF identified 21-hydroxylase on Western blot, while eight IF-positive sera were 21-hydroxylase-negativ e. Five sera weakly recognized 17 alpha-hydroxylase in Western blots, but all of these were also positive for 21-hydroxylase. In 13 cases (1 2 women), the sera also reacted with testicular Leydig cells, and nine of these identified the side-chain cleavage (SCC) enzyme. Other clini cally evident organ-specific autoimmune disorders were present in 40% of the 97 patients and abnormal titres of organ-specific antibodies we re found in 60% of the patients. CONCLUSIONS In idiopathic Addison's d isease, autoantibodies against 21-hydroxylase are found in a majority of cases and this represents an important diagnostic tool. The enzyme 17 alpha-hydroxylase does not seem to constitute a major autoantigen i n Addison's disease. In a subgroup of patients with autoantibodies to gonads, antibodies to SCC are produced, often in parallel with antibod ies to 21-hydroxylase. In yet another subgroup the specificity of auto antibodies giving positive immunofluorescence is still unknown. Three patients revealed a polyendocrine syndrome which clinically resembles autoimmune polyendocrine syndrome (APS) type I, but serologically corr esponds to APS type II. Polyendocrine disorders are often associated w ith Addison's disease, and screening, including quantification of auto antibodies, may help to identify those at risk of developing associate d autoimmune disorders.