Effects of prolonged adrenocortical stimulation on patients with rheumatoid arthritis.

The only practical means of maintaining a raised output of steroids from the adrenal cortex is by the daily intramuscular or subcutaneous injection of corticotropin in a medium that delays absorption. The effects produced by such therapy depend upon -the amount by which the daily output of steroids is raised above the starting level and the length of time that the raised level is maintained. The only practical means of measuring the output of the adrenal cortex is by assaying, in 24-hr specimens of urine, the metabolites of the principal hormone cortisol (hydrocortisone). The study reported here covers 4+ years, and is a follow-up of a previous study (West and Newns, 1955). For the first 18 months the metabolites of cortisol were assayed by the "17-ketogenic steroid" (17 KGS) method (Norymberski, Stubbs, and West, 1953) and since then they have been assayed by the "total 17-hydroxycorticosteroid" (17(OH)CS) method (Appleby, Gibson, Norymberski, and Stubbs, 1955). Both assays were developed at this Centre. The results of these two assays do not differ appreciably except in the rare disorders of the adrenal cortex. Consideration of the value and limitations of these assays will be referred to under the heading "Discussion" below but it can be stated at this point that a study of some 3,000 assays in conjunction with the clinical state of the patients concerned leaves no doubt that the anti-rheumatic effects produced by stimulating the adrenal cortex vary directly with the urinary output of 17 KGS and 1 7(OH)CS. There have been many brief reports of the effects produced by corticotropin therapy and not a few describing undesirable effects, but rarely, if ever, 'have these reports included a statement of the level of adrenocortical stimulation achieved or of its duration. In view of the undesirable effects reported, this paper will take account of every