Effect of alternate-day, single-dose, corticosteroid therapy on pituitary-adrenal function.

Therapeutic doses of ACTH given daily and maintained for more than 2 years in patients with poly-arthritis do not normally suppress hypothalamic-pituitary-adrenal (HPA) responsiveness to the stresses of insulin hypoglycaemia or surgery (Carter and James, 1970a, b). By contrast, corticosteroids in daily doses equivalent to 7 5 mg. or more of predni-solone will impair pituitary-adrenal function in most patients, but our attempts to mitigate their suppres-sive effect by combining steroid treatment with intermittent ACTH in reasonable therapeutic dosage were unsuccessful (Carter and James, 1970c). In fact, pituitary-adrenal suppression as judged by response to insulin-induced hypoglycaemia appeared to be increased rather than offset. Thus it seemed that the administration of therapeutic daily doses of steroids inevitably causes suppression. Using a daily administration schedule, this suppression can be diminished by single as opposed to divided daily doses of steroid (Myles, Bacon, and Daly, 1971). In recent years, too, physicians treating patients with other chronic diseases, such as the nephrotic syndrome, ulcerative colitis, asthma, and sarcoidosis, in which much larger maintenance doses ofcorticosteroids tend to be used, have been exploring intermittent regimes with a view to diminishing some of the side-effects, including Cushingoid features, growth inhibition in children, osteoporosis, and impairment of HPA function, without loss of therapeutic effect 1969). The most promising administration schedule appeared to be by a single dose once every 48 hours, and it seemed important to us to try to establish whether this method of steroid administration, especially as applied to the relatively small maintenance doses employed in the management of rheuma-toid disease, would be therapeutically practicable, and would preserve the integrity of the HPA axis; this report relates our experience with such a regime in patients with active chronic polyarthritis. Material and methods Of fourteen patients studied, twelve women and two men, ten were suffering from active classical rheumatoid arthritis, according to the A.R.A. criteria (Ropes, Bennett, Cobb, Jacox, and Jessar, 1958), two from probable rheumatoid arthritis, and two from psoriatic arthropathy. Their mean age is 48 years (range 15 to 73) and the mean duration from onset of disease is 8 years (range 1 to 18). Only patients who were considered to require 10 mg. or more of prednisolone daily were included, and they were given the sum of their 48 hour four-times-a-day steroid requirement as a single dose after breakfast every other day. Seven patients (Group 1) who had not received steroids previously were started …