Acquired resistance to corticotropins.

Corticotropin, which may be defined as a pituitary extract that will directly stimulate the adrenal cortex to secrete its predominantly "glucocorticoid" hormones, has been in general use for about 5 years. In spite of this, its use as a therapeutic agent has not been defined. There are two reasons for this state of affairs. The first is that most physicians have assumed that the administration of synthetic corticosteroids (i.e. cortisone, delta-l cortisone, etc.) amounts to the same thing as stimulating the adrenocortex. In consequence they have used only the more easily administered form of treatment. There is little evidence yet to prove or disprove this assumption, but on theoretical grounds it is not justified. The second reason is that much difficulty has been experienced in inducing and maintaining a therapeutic level of adrenocortical stimulation. This has discouraged physicians in their use of corticotropin and has prevented any valid trials of its use as a therapeutic agent. A study of the effects of prolonged adrenocortical stimulation upon the course of rheumatoid arthritis and ankylosing spondylitis was begun at this centre 3 years ago. After 18 months the therapeutic results were encouraging (West and Newns, 1955), but since that time the study has been brought almost to a halt because of the failure of the available "highly purified" corticotropins to maintain adrenocortical stimulation in many patients. Most of the observations made on acquired resistance to corticotropin that are reported below were incidental to this study. Forsham (1955) stated that he had not found the commercially available "highly purified" corticotropin gels to induce refractoriness or hypersensitivity, it being well known that the earlier preparations (not oxycellulose purified) did so. In this paper evidence is presented which shows that on prolonged administration the development of refractoriness to highly purified corticotropin is common. In addition to refractoriness allergic