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Disadvantages of systemic corticosteroids are widely recognized and perhaps the most serious is suppression of the pituitary-adrenal axis. The addition of exogenous corticosteroids to the systemic circulation is detected by the pituitary gland. In response the pituitary gland reduces its own release of adrenocorticotrophic hormone. ACTH normally stimulates the adrenal glands to release their natural corticosteroids, but with reduced levels of ACTH this does not happen. With prolonged use of anti-inflammatory corticosteroids, the adrenal glands atrophy and lose their ability to synthesize their natural corticosteroids.