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Cortisol is the major adrenal glucocorticoid steroid hormone, normally under feedback control by pituitary ACTH and the hypothalamus. Causes of low cortisol include pituitary destruction or failure, with resultant loss of ACTH to stimulate the adrenal, and metabolic errors or destruction of the adrenal gland itself (tuberculosis, histoplasmosis, adrenogenital syndromes). The diagnosis of hypoadrenalism normally requires confirmation with ACTH stimulation, due to the circadian rhythms of cortisol and other factors. Causes of increased cortisol, which initially may present as loss of normal diurnal variation, include pituitary overproduction of ACTH, production of ACTH by a tumor (notably oat cell cancers), and adrenal adenomas.