A Clinical Study on the Effect of Extrinsic Corticotropin on the Pituitary-Adrenocortical Function

Abstract

The effects of ACTH preparations on the pituitary-adrenocortical function remain to be clarified in more respects than those of steroid drugs. In the present study, the author investigated the effect of synthetic ACTH-Z on the pituitary-adrenocortical function in a series of 76 patients under synthetic ACTH-Z therapy using the daily urinary excretion of 17-KGS as an index. The results are summarized as follows :
1) The administration of synthetic ACTH-Z in a dose of 0.25 mg or 0.5 mg q.d. was followed by a gradually declining tendency of the daily urinary excretion of 17-KGS. More particularly, after 1.5 months of synthetic ACTH-Z medication at either of these dosage levels, the response of urinary 17-KGS was found to have decreased to about 1/2 of its level at the beginning of medication.
2) The responsiveness of urinary 17-KGS was well maintained even after 3 months of intermittent doses of 0.25 mg of synthetic ACTH-Z (3 times a week, or every other day).
3) Synthetic ACTH-Z, when used in a smaller dose of 0.125 mg daily, produced a minimal stimulating effect on the adrenal cortex. When administered in a less frequent (twice weekly) dose of 0.25 mg, synthetic ACTH-Z failed to prevent or counterbalance atrophy of the adrenal cortex induced by small doses of steroid drugs (average total dose equivalent to 12.2 mg of prednisolone).
4) With the purpose of activating the steroid-atrophied adrenal cortex, synthetic ACTH-Z was administered in a daily or intermittent (every other day, or 3 times a week) dose of 0.25 mg. With the daily dosage regimen, the atrophied adrenal cortex temporarily exhibited a good response, but its responsiveness soon decreased again, and in the end, synthetic ACTH-Z administered in this mode failed to activate the adrenal cortex. With the intermittent dosage regimen, on the other hand, a tendency toward recovery of adrenocortical responsiveness was observed in half the cases studied. In the remaining half receiving steroids over a prolonged period of time, recovery of adrenocortical responsiveness was not attained to any appreciable extent.
These results might be interpreted as suggesting that the administration of synthetic ACTH-Z in an intermittent dose of 0.25 mg or 0.5 mg is advisable for the activation of the atrophied adrenal cortex. If this therapeutic regimen fails to initiate a tendency to recovery of adrenocortical responsiveness in a matter of a month or two, this implies that there is atrophy of the adrenal cortex severe enough to invalidate the therapeutic use of synthetic ACTH-Z.
5) The response of the adrenal cortex to 0.25 mg doses of synthetic ACTH-Z was distinctly suppressed by the concomitant use of steroids in 10 mg doses (as calculated on a prednisolone basis). Likewise, the response of the adrenal cortex to 0.5 mg doses of synthetic ACTH-Z was suppressed to 78%, 46% and 16%, respectively, by the conjoined use of steroids in doses of 20 mg, 30 mg and 40 mg or above.
6) The urinary 17-KGS level returned to the normal range in no more than 6 to 10 days after treatment with synthetic ACTH-Z given at 0.25 mg daily for 9 to 62 consecutive days.
From these findings it is inferable that recovery of the hypothalamo-pituitary-adrenocortical function following the discontinuation of synthetic ACTH-Z is far faster than that after the withdrawal of steroids.