副腎皮質ホルモン使用時の下垂体副腎皮質系機能の抑制と回復に関する研究

抄録

The present study was undertaken to investigate suppression of the pituitary-adrenocortical function by long-term corticosteroid therapy and spontaneous recovery from such a suppressant drug effect. Sixty patients who were on corticosteroids (hereinafter their dosage is expressed as the equivalent of prednisolone) given at 10 to 40 mg initially and then on a gradually decreasing basis down to below 10 mg currently or who had already been withdrawn from such a drug regimen were involved in the study and analysed for baseline values for plasma cortisol. These patients were evaluated for the functional status of the pituitary-adrenocortical system in relation to varying combinations of such factors as the total dose of corticosteroids, the duration in days of medication, the duration in days of medication at reduced dosage levels, and time in days elapsed from cessation of medication. The results led to the following conclusions :
(1) In patients receiving corticosteroids at such daily dosage levels as are reduced gradually to 7.5 mg or below within the duration in days as defined by the inequality Y≥8.4X + 222 (where Y stands for total dose given and X stands for the duration in days of administration), the pituitary-adrenocortical function is assumed to be in a state of being suppressed.
When corticosteroids have been given at daily dosages reduced gradually to 7.5 mg or below within the duration in days as determined by the inequality Y≤6.8X + 140 (where Y and X, respectively, stand as mentioned above), the pituitary-adrenocortical function of the recipient patient is considered to be in a state either of being not suppressed or of being recovered from suppressant drug effect.
(2) In cases where corticosteroid therapy is started with a moderate dosage, then reduced to a low dosage level or stopped within a relatively short period of time, the recipient patient can be safely withdrawn from the drug therapy without suppression of the pituitary-adrenocortical function if the dosage schedule is in line with the inequality Y≥5.9X + 331 (where X denotes the duration in days of medication and Y, total dose).
These results led the author to formulate a model of a corticosteroid dosage schedule which is reasonably free from the risk of causing pituitary-adrenocortical insufficiency. More particularly, the dosage of corticosteroids is reduced by a 5 mg decrement at regular intervals of 5, 8, 13, 27 and 103 days, respectively, when the initial daily dose is 30, 25, 20, 15 and 10 mg. By following this dosage regimen one might expect safe withdrawal from corticosteroid therapy without risking suppression of the pituitary-adrenocortical function.
(3) Corticosteroid therapy, when given at a dosage of 7.5 mg or less daily, is considered to have little suppressant effect on the pituitary-adrenocortical function. In cases where the pituitary-adrenocortical function has been suppressed as a result of corticosteroid therapy, the use of the drugs at a maintenance dose of 7.5 mg or less per day may be reasonably anticipated to result in spontaneous recovery of the suppressed function with avoidance of withdrawal syndromes.
(4) In cases in which the pituitary-adrenocortical function has been suppressed by the prolonged use of corticosteroids and daily dosage levels average less than 5 mg for the last one month, the same function is very likely to have already been recovered unless the total dose exceeds 1.6 g. Likewise, where an average daily dose of less than 5 mg has been given for the last 3 and 6-12 months, and if the total dose does not exceed 2.4 g and 4.9g, respectively, the pituitary-adrenocortical function in all probability has already been restored.