The damage associated with corticosteroid therapy may not become apparent until the consequences are catastrophic.Why Getting Incontinence Treated is Important Consequently, chronic use of these powerful drugs is limited by their slow, cumulative side-effect profile. However, despite continual effort, successful separation of clinical efficacy from deleterious side effects has not been achieved. In the intervening years, synthetic corticosteroid analogs that separate antiinflammatory and electrolyte balance effects were developed. During this period, the field of corticosteroid therapy rapidly advanced as the majority of synthetic corticosteroid analogs available today were developed and practical methods of plasma cortisol determination were identified.
Intense investigation of these compounds was spurred by this widespread clinical interest, and in the subsequent decade, most of the biochemistry involved in the synthesis and metabolism of adrenocortical steroids was elucidated. In 1949, Hench 8 first reported the efficacy of cortisol and ACTH in the treatment of rheumatoid arthritis, an observation that was quickly extended to therapeutic applications in a wide variety of diseases. 6, 7 During this time, several bioactive steroids, including cortisol and aldosterone (the principal active corticosteroids in humans) were isolated from the adrenal cortex and characterized. 3, 4 Hypercortical syndrome was described by Cushing in 1932, 5 and in the 1940s and 1950s, adrenocorticotropic hormone (ACTH) was identified in the anterior pituitary and described as a stimulator of the adrenal cortex. 1, 2 Subsequent research categorized the effects of adrenal insufficiency into two distinct groups: those due to electrolyte imbalance and those due to altered carbohydrate metabolism.
This chapter reviews corticosteroid pharmacology and physiology, discusses the use of these hormonal agents in the treatment of neoplasms, and presents the currently understood mechanism of action of corticosteroids in the context of their therapeutic efficacy.Īs early as the mid-nineteenth century, it was observed that a lack of functional adrenal glands is incompatible with life. Since their first clinical application, intensive research has expanded our understanding of the physiology, biochemistry, and pharmacology of steroids and has led to a large body of literature addressing the therapeutic use and harmful side effects of corticosteroids. Cortisol and its synthetic analogs have been in widespread clinical use for the treatment of a variety of disorders for more than 50 years.
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