The Changing Clinical Spectrum of Adrenal Insufficiency

The clinical spectrum of primary adrenal insufficiency has changed substantially over the past decade as a result of the emergence of new disease patterns, improved understanding of clinical presentations, and the impact of molecular genetics. I comment here on five clinical entities that have emerged as new diagnostic or therapeutic challenges in the 1990s.

Adrenal insufficiency is increasingly recognized in patients with AIDS [1-3], and it correlates with stage of progression of HIV infection. More than 50% of patients with AIDS have pathologic evidence of necrotizing adrenalitis, but the degree of adrenal destruction is usually less than 50%. Clinical adrenal insufficiency occurs in less than 5% of patients with AIDS because its production requires that more than 90% of the adrenal cortex be destroyed. In adrenal insufficiency due to AIDS, a shift from mineralocorticoid and androgen production to glucocorticoid production occurs, possibly as a response to the stress of severe illness. However, hyponatremia in patients with AIDS is usually related to the syndrome of inappropriate vasopressin secretion and not to adrenal insufficiency [4].

The pathogenesis of adrenal insufficiency in AIDS can be related to three independent factors [1, 2]. First, cytomegalovirus infection accounts for more than 50% of cases of adrenal insufficiency in AIDS. Other pathogens that can cause this condition include Mycobacterium avium-intracellulare, M. tuberculosis, fungi, Toxoplasma species, and Pneumocystis species. Second, medications can alter steroid secretion or cause changes that mimic adrenal insufficiency. For example, the antifungal agent ketoconazole decreases adrenal steroidogenesis; rifampin, phenytoin, and opiates increase steroid …