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Unexplained weight loss may be a sign of malignancy, and weight loss is common in advanced cancer. Decreased appetite and food intake contribute to but do not entirely account for the weight loss. The weight loss is largely from skeletal muscle and adipose tissue, with relative sparing of c (i.e., liver, kidney, and heart). Although tumors commonly exhibit high rates of glycolysis and release lactate, the energy requirement of the tumor probably does not explain weight loss because weight loss can occur with even small tumors. In addition, the presence of another energy-requiring growth, the fetus in a pregnant woman, does not normally lead to weight loss. Several endocrine abnormalities have been recognized in cancer patients. They tend to be insulin-resistant, have higher cortisol levels, and have a higher basal metabolic rate compared with controls matched for weight loss. Two other phenomena may contribute to the metabolic disturbances.

Some tumors synthesize and secrete biologically active peptides such as ACTH, nerve growth factor, and insulin like growth factors, which could modify the endocrine regulation of energy metabolism. It is also possible that the host response to a tumor, by analogy to chronic infection, includes release of interleukin-1, interleukin 6, and tumor necrosis factor alpha by cells of the immune system. TNF alpha is also called cachexin because it produces wasting. TNF alpha and IL-1 may act in a paracrine fashion, as plasma levels are not elevated. They do induce the synthesis of IL-6, which has been detected in cachectic patient’s blood at increased levels. These cytokines stimulate fever, proteolysis, lipolysis, and the synthesis of acute phase reactants by the liver. It seems likely that additional, as yet uncharacterized, cytokines play a role in cancer Cachexia, and that the mechanism for this phenomenon may vary with different tumor types.