History of the development of corticosteroid therapy.

The first clinical evidence that an extract of animal adrenocortical tissue could counteract human adrenal failure was demonstrated in 1930. As chemical analyses of cortical extracts proceeded, mainly in the laboratories of Kendall at the Mayo Clinic and Reichstein in Zurich, it became evident that there is not one cortical hormone, but that all are steroids. By 1940 it was understood that there are two categories: those that cause sodium and fluid retention and those that counteract shock and inflammation. Structurally the presence or lack of oxygenation at C11 on the steroid skeleton was critical. In 1948 the first patient with rheumatoid arthritis was treated with cortisone and soon thereafter other rheumatologic patients received cortisone or, to stimulate native cortisone production, ACTH. Oral and intra-articular administration of cortisone and hydrocortisone began in 1950-51. Several lines of research to produce cortisone semi-synthetically showed some success by 1952. Between 1954 and 1958 six synthetic steroids were introduced for systemic anti-imflammatory therapy. By 1960 all of the toxic effects of chronic corticosteroid administration had been described, as well as protocols to withdraw such drugs while minimising symptoms of cortical insufficiency. To enable use of lower corticosteroid dosages, companion use of non-steroidal anti-inflammatory drugs began in the late 1950s, with phenylbutazone the first. In the 1970s the introduction of methotrexate and other anti-metabolites further circumscribed the dosages and indications for corticosteroids in the rheumatic diseases.