Hypothalamo-pituitary-adrenal function in patients on long-term adrenocorticotrophin therapy.

Adrenocorticotrophic hormone (ACTH) is of value in the treatment of a number of diseases which respond to corticosteroid therapy, and has been preferred to corticosteroids themselves by several clinicians on the grounds that side-effects are fewer and withdrawal easier (Savage, Copeman, Chapman, Wells, and Treadwell, 1962), that there is a better clinical response in rheumatoid arthritis (West, 1957), and that there is no growth retardation in children (Friedman and Strang, 1966). The suppressive effect of prolonged corticosteroid therapy on the hypothalamopituitary-adrenal (HPA) axis has been well-documented, and the danger that patients so treated may have an inadequate response to stress is universally recognized. Whether a similar risk of suppression exists after ACTH therapy is less clear. Severe operative shock has been reported (Hayes and Kushlan, 1956) but there are far fewer reports of such shock following ACTH than following corticosteroid therapy. This may be because ACTH is a less common form of treatment or it may indicate that ACTH is inherently less likely to cause suppression. ACTH is used frequently in this department for the treatment of rheumatoid arthritis with good clinical results (Savage, Davis, Chapman, Wickings, Robertson, and Copeman, 1959). Pituitary-adrenal function in twelve ACTH-treated patients has been assessed by the metyrapone test, with only one abnormal result (Savage and others, 1962). Holub, Wallace, and Jailer (1960) also found a normal response in all of six patients tested but acute suppression of the metyrapone response has been reported in normal subjects given short-term highdosage ACTH therapy (Solem and Brinck-Johnsen, 1961; Plager and Cushman, 1962). Several different tests of pituitary-adrenal function have been developed in addition to the metyrapone test, and it is now recognized that no single test can adequately assess the functional integrity of the entire HPA axis. These tests have been used to assess corticosteroid-treated patients and patients on intermittent ACTH therapy (Nelson, Mackay, Sheridan, and Weaver, 1966), but their use has not been reported in patients on long-term daily ACTH therapy. It was therefore decided to investigate a group of such patients using a variety of test procedures in each subject, as it is important to elucidate the effect of long-term ACTH therapy on the HPA axis.