コルチコイド大量療法と視床下部下垂体副腎皮質機能

急性白血病を中心に

抄録

The effect of massive doses of synthetic corticoids, with an initial dose equivalent to 200 mg/day prednisolone, on the hypothalamo-pituitary adrenocortical function and its reserve in the acute leukemic patients was studied. On the basis of results obtained, the adequacy of massive administration of corticoids was discussed.
The cases employed in the study were a total of 26 patients (31 therapeutic courses). They were determined for the daily urinary excretion of Porter-Silber chromogens, Zimmermann chromogens and 17-KGS and then for their consequent response to i. m. injection of 25 unit ACTH-Z or to oral administration of 3 gm SU 4885, before and after treatment. In postmedication follow-ups the 7th day of discontinuance of treatment was taken as Day 1.
i) Both the daily urinary excretion of corticosteroids and the response to ACTH-Z & SU 4885 of the patients with acute leukemia before treatment showed no significant difference from those of the control group, though varied considerably. This means that there generally is no demonstrable dysfunction of the hypothalamo-pituitary adrenocortical system in acute leukemia.
ii) Since, however, there was evidence of dysfunction of the hypothalamo-pituitary adrenocortical system and of reduction in its reserve in some cases, the possible influences of clinical factors on them were studied. The clinical factors examined included age, sex, bleeding tendency, high fever, hepatic enlargement, hepatic insufficiency, A/G ratio, hematocrit, platelet count, WBC & NCC. On each of these factors, the patients were divided into 2 groups as in Fig. 5 to determine whether there is statistically any significant difference in urinary excretion of corticosteroids and response to ACTH-Z between both groups. None of these factors were found to have any conspicuous effect on them.
iii) The 24 hours' urinary excretion of corticosteroids following treatment with massive doses of corticoids in the acute leukemic patients showed no significant difference from that before treatment or of the control group. This is presumably due to our careful reduction of dosage with subsequent tapering at 5 mg daily for two weeks.
iv) The response to ACTH-Z after treatment, as compared to that before treatment or of the control group, was reduced with a significant difference (P<0.05), indicating a reduced adrenocortical reserve following treatment with massive doses of corticoids. Similarly, the response to SU 4885 was found significantly reduced (P<0.05) after treatment as compared to that before treatment or of the control group. But it is impossible to determine whether this change is of hypothalamo-pituitary or of adrenocortical origin.
v) Throughout the therapeutic courses, no clinical and laboratory findings suggestive of hypothalamo-pituitary adrenocortical insufficiency were obtained in any instance.
vi) There was no inverse correlation between the 24 hours' excretion as well as response to ACTH-Z or SU-4885 of urinary corticosteroids after treatment and the sum of administered doses of corticoids as prednisolone or duration (days) of corticoid therapy. It is unlikely, therefore, that the hypothalamo-pituitary adrenocortical function and its reserve reduce with increasing doses and with a longer duration of administration, which is given within the dosage range employed in the present study.
vii) The recovery of the adrenocortical reserve appears to be somewhat retarded after treatment with “massive” doses than with “ordinary” ones. However, the reduction in the adrenocortical reserve produced by treatment with massive doses is by no means irreversible, the reserve being found normalized after 8 months in all instances.
It has been generally accepted that corticoids, when used not as a replacement therapy but for their pharmacologic effects, produce the suppression of the hypothalamo-pituitary adrenocortical system. These results, however,