The causes of primary hypoadrenalism are listed in TabieJ,. Tuberculosis, once a major cause of primary hypoadrenalism, has been largely replaced by autoimmune (Addison's) disease (either isolated or as part of a polyglandular autoimmune syndrome) as the leading cause of hypoadrenalism in the industrialized countries. Addison's disease has a marked female predilection and usually occurs in the third to fifth decades of life. Recently, AIDS has increasingly been recognized as a cause of primary adrenal dysfunction due to necrotizing adrenalitis.

Table 1 Causes of primary hypoadrenalism

Disseminated fungal infections, particularly histoplasmosis, can cause adrenal insufficiency in endemic areas. Metastatic infiltration of the adrenal glands is common, particularly in lung and breast cancer, but clinically recognized adrenal insufficiency is uncommon. Some drugs (e.g. ketoconazole, etomidate, suramin) inhibit cortisol biosynthesis, whereas others (e.g. rifampin (rifampicin), phenytoin) accelerate the metabolism of cortisol and these can induce adrenal insufficiency in patients with a limited hypothalamic-pituitary-adrenal axis reserve.

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