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  • Title: A clinical and immunological study of adrenocortical insufficiency (Addison's disease).
    Author: Irvine WJ, Stewart AG, Scarth L.
    Journal: Clin Exp Immunol; 1967 Jan; 2(1):31-70. PubMed ID: 5340030.
    Abstract:
    Fifty-one patients with adrenocortical insufficiency were subdivided into three groups according to the nature of their adrenal disease; twelve patients with idiopathic, twenty-three patients with probable idiopathic and sixteen patients with tuberculous adrenal insufficiency. The importance of objective confirmation of a clinical diagnosis of adrenal insufficiency is stressed and the difficulties of classification of many patients with adult onset adrenal insufficiency are discussed. Idiopathic and probable idiopathic adrenal insufficiency had a sex ratio that was predominantly female (2·5:1) with a mean age of onset of 33 years. Antibodies to adrenal cortex were detected by the methods of immunofluorescence and complement fixation. They were detected in the serum of 80% (20:25) of the females with idiopathic or probable idiopathic adrenal insufficiency and in only 10% (1:10) of the males. The titre of the adrenal antibody was low (≤32) as tested either by immunofluorescence or complement fixation. The serum of only one patient with tuberculous adrenal insufficiency reacted with adrenal tissue in the complement fixation test but the immunofluorescence method showed that this serum reacted with the vascular endothelium and not the secretory cells. No correlation was observed between the duration of the clinical illness and the presence, or absence, or titre of the adrenal antibody. Adrenal antibody was not detected in the sera of fifty-one control subjects matched for age and sex. Four of sixty-nine patients with lymphadenoid goitre, one out of ninety-three patients with diabetes mellitus and none of 230 patients with thyrotoxicosis, primary hypothyroidism or pernicious anaemia had antibody in the serum specific for adrenocortical secretory cells. There is a clinical and immunological overlap between idiopathic adrenal insufficiency and other diseases associated with autoimmune phenomena— thyroid disease, atrophic gastritis and hypoparathyroidism. It is concluded that idiopathic adrenal insufficiency belongs to a group of diseases that are characterized clinically by onset predominantly in females, by aggregation in the same group of patients, by familial tendency, by the presence of organ-specific antibodies in the serum and histologically by lymphocytic infiltration and atrophy. While only one tissue of the group may be predominantly affected, the other tissues are frequently the site of subclinical disease. There is no set order in which the different tissues are affected. Serological evidence of adrenalitis is rare in patients with thyroid disease or pernicious anaemia, but thyroiditis and gastritis are common in patients with adrenalitis. Two autopsies on patients with idiopathic adrenal insufficiency are described. One case had the classical features of adrenal atrophy with gross reduction in size of the glands, islets of secretory epithelial cells and a moderate degree of lymphocytic infiltration. In the other case, the adrenal glands were only slightly less than normal in size, there were few adrenal epithelial cells and a dense lymphocytic infiltration and some fibrosis. The histology resembled that of the thyroid in Hashimoto goitre. If the term `autoimmune' adrenalitis is to be substituted for idiopathic adrenal insufficiency, it should be on the understanding that while autoimmune mechanisms may be of primary importance in the pathogenesis of adrenal disease this has yet to be proven.
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