1968 Volume 44 Issue 9 Pages 1025-1036,970
The purpose of the present study is to clarify the patho-physiology of the pituitary-adrenocortical insufficiency induced by glucocorticoid treatment, and to find out preventive means against this pituitary-adrenocortical insufficiency. Pituitary adrenocortical function in patients with various non-endocrine disorders who had been treated with glucocorticoid for long terms, was studied by measuring daily urinary 17-OHCS excretion. Urine samples were collected daily for a period of 12 days beginning from the 1st day after glucocorticoid treatment was stopped. Oral SU-4885 test (3.0 gm./day in 6 divided doses) and intramuscular ACTH stimulation test (20 I.U. of ACTH-Z for 3 successive days) were performed on the 3rd test day and 9-11th test days, respectively. Urinary 17-0HCS excretion was measured by means of a modification of the method of Reddy, Jenkins and Thorn.
1) Eighteen subjects after long-term glucocorticoid treatment were studied.
a) Seven patients treated with less than 2000 mg. (prednisolone equivalent) of glucocorticoid in a total dose and for less than 12 months, gave variable results, but many of them showed reduced response to SU-4885 and delayed response to ACTH. These results suggest that glucocorticoid treatment brings about secondary adrenocortical insufficiency by its suppressing effect on pituitary ACTH secretion.
b) Eight out of 11 patients treated with more than 3000 mg. of glucocorticoid in a total dose and for more than 12 months, showed reduced response to SU-4885 and delayed or reduced response to ACTH. Four of these 8 patients treated with glucocorticoid for more than 20 months, showed reduced responses to SU-4885 and to ACTH.
c) The remaining 3 patients who were maintained with a daily dose of less than 5 mg. of prednisolone for more than one year before the cessation of the treatment showed normal response to SU-4885. There seemed to be a reverse relationship between final daily dose of glucocorticoid and response to SU-4885.
d) A patient treated with glucocorticoid for 3 years showed reduced pituitary adrenocortical function even on the 53rd day after the cessation of the treatment. It seems to take a long time to recover from the pituitary-adrenocortical insufficiency after longterm glucocorticoid treatment.
2) In comparison with the administration of glucocorticoid alone, a combined administration of 20 mg. of H.M.D. daily with glucocorticoid in 4 patients caused no significant change in response to SU-4885 but gave a better response to ACTH after the cessation of the treatment. Daily urinary excretion of 17-OHCS was measured in subjects treated with gradually reducing doses of betamethasone alone or in combination with 20 mg. of H.M.D. daily for 4 weeks. Although the decrease of urinary 17-OHCS during the treatment seemed to be more marked in the betamethasone-H.M.D. group than in the betamethasone group, the increase of urinary 17-OHCS after the cessation of the treatment appeared sooner in the betamethasone-H.M.D. group. These results lead to a conclusion that the combined administration of anabolic steroids with glucocorticoid may partially improve the pituitary adrenocortical hypofunction after glucocorticoid treatment.
3) Treatment with a daily dose of 20 I.U. of ACTH-Z for 5 successive days immediately before the cessation of glucocorticoid treatment in 4 patients improved the response to ACTH-Z, especially to the first dose of ACTH-Z, but showed the reduced response to SU-4885. This may be due to the fact that ACTH administration suppresses pituitary ACTH secretion in spite of the improvement of adrenocortical reserve.
