1 Aetiology and pathogenesis of hormonal and metabolic disorders in HIV infection

Many hormonal and metabolic disturbances are documented in HIV infection, the most important of which is the wasting syndrome associated with progressive HIV infection. We are only now beginning to understand the pathogenesis of these disturbances. In rare cases, infiltration of endocrine tissue by secondary infectious or malignant processes is the underlying cause of hormonal insufficiency. In most instances, however, hypofunction is secondary to the well-known effects of severe illness. Similarly, hyperfunction of the adrenal axis along with many of the derangements in substrate metabolism are also likely to be secondary to severe illness, perhaps through activation of cytokines and other molecules. Specific disturbances in asymptomatic patients are more difficult to document and may represent unique and as yet unexplained manifestations of HIV disease. Hypermetabolism and depletion of lean body mass are most profound in the acutely ill patient with active secondary infection. At this stage, the HIV-infected patient is in a catabolic state and adaptive mechanisms which normally decrease energy expenditure and preserve lean body mass are either overridden or not operative. Strategies to reverse the catabolic state and diminish wasting are only now being developed.