抗炎症性ステロイドの下垂体・副腎皮質機能抑制作用に関する研究

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  • Study of the Inhibitory Effect of Anti-inflammatory Corticosteroids upon Pituitary-Adrenocortical Function
  • コウエンショウセイ ステロイド ノ カスイタイ フクジン ヒシツ キノウ ヨクセイ サヨウ ニ カンスル ケンキュウ

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It is well known that anti-inflammatory steroids have an inhibitory effect upon the pituitary-adrenocortical function (P-A function). This fact is clinically important, because the patients who have been given these steroids for a long-term period have chronic and subclinical adrenocortical hypofunction. We often observe that they have acute adrenocortical insufficiency when they are exposed to stress.<BR>Furthermore, this inhibitory effect has been widely used in the diagnostic procedure in differentiating adrenal hyperplasia from adrenal tumor (so-called suppression test) or the treatment for adrenogenital syndrome.<BR>Recently, some reports suggest that anabolic steroids may prevent this inhibitory effect upon the P-A function.<BR>The present study describes : (I) the minimal suppressive dese of dexamethasone and the suppression test in the patients with pituitary and/or adrenocortical dysfunction, (2) the adrenocortical reserve in the patients with long-term steroid therapy, and (3) the influence of anabolic steroids on the inhibitory effect of anti-inflammatory steroids.<BR>Exp. 1 Suppression test <BR>Dexamethasone was given by mouth every 6 hours for 4 days. Collections of 24-hour urine were made and total 17-OH-CS was determined by a modification of the method of Reddy, Jenkins and Thorn (1952) or Glenn and Nelson (1953).<BR>The results were as follows : <BR>1. The subjects with normal P-A function (8 cases) underwent no cnange in their P-A function by the administration of 0.25 mg. of dexamethasone per day, but complete suppression occured with a dosage of more than 0.5 mg. per day. It was obvious that in spite of the administration of the same dosage, the day of maximal suppression and escape phenomenon after steroid medication, showed individual variations. In some cases, after the withdrawal of dexamethasone, so-called rebound phenomenon was observed.<BR>2. Two cases of Cushing's syndrome due to adrenal hyperplasia showed no adrenal suppression by the administration 0.5 mg. of dexamethasone per day. When these patients received 6.0 mg. or 2.0 mg. per day, they were showed a complete suppression. In 2 cases of Cushing's syndrome due to adrenal tumors, it was clear that no adrenal suppression was observed by the administration of 6.0 mg. of dexamethasone per day.<BR>3. In hyperthyroidism (16 cases) slight or moderate suppression was observed even by the dosage of 0.25 mg. per day.<BR>4. Two cases of acromegaly (one with diabetes mellitus) showed no suppression by the dosage of 0.5 mg. per day. In one case, after radiation therapy with 60Co of 6000 r in total dose, no adrenal suppression was observed by the dosage of 0.5 mg. per day.<BR>Exp. 2. Arenocortical reserves in the steroid-treated patients.<BR>So-called adrenocortical reserves were estimated by use of ACTH stimulation. 40 I.U. of ACTH-Z was given intramuscularly at 6.00 a.m. for 3 days.<BR>The results were as follows : <BR>1. In 15 cases ACTH stimulation was performed within 5 days after the cessation of steroid therapy. Urinary output of total 17-OH-CS following ACTH stimulation in the patients treated with anti-inflammatory steroids were significantly smaller than control subjects with normal P-A function. A significant negative correlation was found between their adrenocortical reserves and the logarithm of duration of steroid treatment or the logaritnm of total doses of administered steroids. There was no significant correlation between their adrenocortical reserves and mean values of daily dosage or ba se line 17-OH-CS before ACTH stimulation.<BR>2. Adrenocortical reserves of 5 patients who had been treated with anti-inflammatory steroids were determined a few months aftes the cessation of steroid theraphy.Three patients who had been treated for 10 days to 30 days showed normal reserves. However, 2 patients who had been treated for 210 or 448 days showed subnormal or decreased reserves.

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