Studies on the Pituitary Adrenocortical Function with Synthetic

Glucocorticoids Therapy, Especially on the Results in the Cases of Alternative Day Treatment

Abstract

This report presents the results on the study of the suppressive effects on the pituitary adrenocortical system by the administration of synthetic glucocorticoids concerning the period, doses and the method of administration, and the results of the clinical significance of the steroid alternative treatment.
Plasma cortisol was measured by the following methods : extraction with chloroform, washing with alkaline solution and the fluorometry with H₂O-CCl₄ partition. Urinary 17-OHCS was measured by Silber-porter's method after hydrolyzing with β-glucuronidase.
ACTH-test was performed by injecting 250 ug of β I-24 synthetic ACTH intramuscularyly, and another test by injecting 25 units of NE-ACTH by drip for 6 hours was adopted.
On the SU-4885 test, the method of administration was 250 mg of metopirone every 2 hours for 24 hours.
The results were summarized as follows :
(1) The diurnal variation of plasma cortisol level in normal human adults was measured. The means and standard deviations were 11.0±3.9 ug/dl at 8.00 a.m., 9.0±3.2 ug/dl at 10.00 a.m., 5.6±2.6 ug/dl at 4 p.m, 4.7±1.7 ug/dl at 10.00 p.m., and 2.8±1.4, ug/dl at midnight, respectively. And they showed regular rhythm and reproducibility.
(2) When 5 mg of hydrocortisone was administered to the normal adult at 0.00 a.m., the plasma cortisol level showed 5 to 10 ug/dl at 2.00 a.m., and a case with 10 mg of hydrocortisone showed 10 to 20 ug/dl, and at 8.00 a.m. the plasma cortisol level showed normal value in the former case, and decreased in the latter case. There was no suppression of cortisol secretion in the case with 2 mg × 4 of hydrocortisone. Therefore, it was observed that the plasma cortisol level was rather low at about 2.00 a.m., and this low level cortisol appeared in diurnal variation of human adult.
(3) The suppression of cortisol secretion at the time of administration of 0.5 mg dexamethasone showed the least in the case administered at 8.00 a.m., and next in the case at 4.00 p.m., and the most in the case at 0.00 a.m. And there was a close corelation between the plasma cortisol level at 8.00 a.m., and the hours after administration of 1.5 mg of dexamethasone.
The greater the doses of dexamethasone were, the more suppressed became the adrenal cortical function, and it took much time to return it to the normal level.
(4) The steroids were administered at 8.00 a.m., every other day for a period of two weeks to two months, and then the plasma cortisol levels were measured at the time just before administering the steroids. There was observed a normal value in all cases in which 30 mg of prednisolone were administerd, in three out of five cases in which 40 mg of prednisolone were administered and decreased in both cases in which 60 mg of prednisolone were administered.
On the rapid ACTH test, there were found normal changes in seven out of eleven cases in the group in which 30 to 40 mg of prednisolone were administered by the alternative day treatment.
The standard ACTH test and the metopiron test were performed in the cases administered with 40 mg of prednisolone every other day for 45 days, and then no fluctuation was found in ACTH test, but significant suppressions were found in three out of four of metopiron tests.
On comparing the alternative day treatment with every day treatment on the basis of the same doses, a decrease of about 50 % of suppression of adrenal gland function was found in the cases receiving the alternative day treatment.
Less countenance change like Cushing's syndrome was found in the cases of alternative treatment, and that change was decreased markedly in the cases administered by the alternative day treatment changed from the every day treatment.
As for the alternative treatment, it was found to be a useful treatment for following diseases : nephrotic syndrome, hepatitis, allergic disease,