Adrenal autoantibodies and organ-specific autoimmunity in patients with Addison's disease

Autoimmune destruction of the adrenal gland is the major cause of Idiopathic Addison's disease, but the significance of 21-hydroxylase autoantibodies and their correlation with the presence of other autoantibodies have not so far been investigated in a larger population of patients with Addison's disease. We have now characterized a cohort of patients with idiopathic Addison's disease (n = 97) regarding the specificity of autoantibodies against the adrenal cortex and, as Addison's disease can be either an isolated condition or part of a polyendocrine disorder, we investigated the presence of organ-specific polyendocrine autoimmunity in this patient population.

Cross-sectional study.

Autoantibodies were analysed with indirect immunofluorescence (IF) on tissue preparations, ELISA and in Western blots using bacterially expressed proteins.

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 as 21-hydroxylase 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-negative. Five sera weakly recognized 17 alpha-hydroxylase in Western blots, but all of these were also positive for 21-hydroxylase. In 13 cases (12 women), the sera also reacted with testicular Leydig cells, and nine of these identified the side-chain cleavage (SCC) enzyme. Other clinically evident organ-specific autoimmune disorders were present in 40% of the 97 patients and abnormal titres of organ-specific antibodies were found in 60% of the patients.

In idiopathic Addison's disease, auto-antibodies 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 in Addison's disease. In a subgroup of patients with autoantibodies to gonads, antibodies to SCC are produced, often in parallel with antibodies to 21-hydroxylase. In yet another subgroup the specificity of autoantibodies giving positive immunofluorescence is still unknown. Three patients revealed a polyendocrine syndrome which clinically resembles autoimmune polyendocrine syndrome (APS) type I, but serologically corresponds to APS type II. Polyendocrine disorders are often associated with Addison's disease, and screening, including quantification of autoantibodies, may help to identify those at risk of developing associated autoimmune disorders.