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Chapter: Medical Immunology: Organ-Specific Autoimmune Diseases

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Addison’s Disease (Chronic Primary Hypoadrenalism)

Addison’s disease can either be caused by exogenous agents (e.g., infection of the adrenals by Mycobacterium tuberculosis) or be idiopathic.

ADDISON’S DISEASE (CHRONIC PRIMARY HYPOADRENALISM)

Addison’s disease can either be caused by exogenous agents (e.g., infection of the adrenals by Mycobacterium tuberculosis) or be idiopathic. The idiopathic form is believed to have an immune basis, since 50% of patients have been found to have antibodies to the micro-somes of adrenal cells (as compared to 5% in the general population) by immunofluores-cence. The autoantibodies directed against the adrenal react mainly in the zona glomeru-losa, zona fasciculata, and zona reticularis and are believed to play the main pathogenic role in this disease, causing atrophy and loss of function of the adrenal cortex. Biopsy of the adrenal glands shows marked cortical atrophy with an unaltered medulla. Abundant in-flammatory mononuclear cells are seen between the residual islands of epithelial cells.

The autoimmune form of Addison’s disease is found frequently in association with other autoimmune diseases, such as thyroiditis, pernicious anemia, and diabetes mellitus; autoantibodies to adrenal cortex are not found in Addison’s disease caused by tuberculosis of the adrenal glands.

Symptoms of Addison’s disease or adrenal insufficiency include weakness, fatigabil-ity, anorexia, nausea, vomiting, weight loss, and diarrhea. Signs include increased skin pig-mentation and vascular collapse and hypotension. Addison’s disease is most commonly found in the fourth and fifth decades of life and is two to three times more frequent in females.

The diagnosis is confirmed by demonstration of antiadrenal antibodies by indirect immunofluorescence. Low plasma cortisol levels and low levels of urine 17-ketosteroids and 17-hydroxycorticoids are characteristic of the disease. Frequent metabolic abnormali- ties include acidosis, hyperkalemia, hyponatremia, low levels of chloride and bicarbonate, and hypoglycemia. Lymphocytosis with eosinophilia may be present.

The treatment of Addison’s disease consists of replacement of both glucocorticoids and mineralocorticoids.


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