ACTHの臨床的研究:第1編 ACTHのCortisol代謝におよぼす副腎外作用について
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It has been reported that besides adrenal stimulating activity ACTH has some biological effects. These extra-adrenal effects of the ACTH include alterations in cortisol metabolism. In patients with essential hypertension and in those with neurosis, a discrepancy was observed between plasma and urinary 17-OHCS. That is, in these patients the plasma 17-OHCS concentration was significantly elevated, while the urinary 17-OHCS was normal or low. In addition, the urinary excretion of ACTH was increased. It was suggested that the discrepancy between the plasma and the urine 17-OHCS could be attributed to the effect of ACTH on cortisol metabolism.<BR>In order to avoid the influence of endogenous cortisol, the extra-adrenal effects of ACTH on cortisol metabolism were investigated in 11 patients with adrenal insufficiency. All of them were free of demonstrable renal and hepatic diseases and showed no increase in plasma free 17-OHCS concentration and urinary 17-OHCS excretion after administration of ACTH.<BR>Cortisol was given orally to the patients in doses of 20 mg twice a day for four days. On the fifth day, a cortisol disappearance test was performed. During the next four days, 40 mg of cortisol was given orally and at the same time 40 units of ACTH-Z (Organon) were injected intramuscularly once daily. On the tenth day, the cortisol disappearance test was performed during the intravenous infusion of 1 mg/Kg of cortisol for 30 minutes with a simultanous intravenous infusion of 50 units of ACTH in 500 ml of 5% glucose for 6 hours. In every case the infusion was started at 10 : 00 a.m. Blood samples were drawn, one, two, four and six hours after infusion, and a concentration of the plasma free 17-OHCS was determined by a modified method of Silber and Porter. The half-life in plasma, the apparent distribution volume (A.D.V.) of administered cortisol and the concentration of plasma free 17-OHCS at zero time (C<SUB>0</SUB>) were calculated.<BR>The urinary free and the total 17-OHCS and 17-ketogenic steroids (17-KGS) were measured in specimens collected for 24 hours during the cortisol administration (40 mg) and also in those collected during and after the cortisol infusion. After extracting 50 ml of urine twice with 50 ml of chloroform, free 17-OHCS was measured by the same procedure as used in the determination of total 17-OHCS. Total 17-OHCS was estimated by utilizing the Porter-Silber reaction after bacterial β-glucuronidase hydrolysis followed by acid hydrolysis. The 17-KGS was measured by a modified method of Few.<BR>In the absence of exogenous ACTH, the concentration of plasma free 17-OHCS, one, two, four and six hours after cortisol infusion were 100.2, 79.9, 32.2 and 16.6μg/dl, respectively on an average of seven cases with adrenal insufficiency. The C<SUB>0</SUB> of plasma free 17-OHCS, the half-life of plasma free 17-OHCS and the ADV of 17-OHCS were 158.0 μg/dl, 68 body weight % and 115 minutes, respectively. In the administration of ACTH, the concentrations of plasma free 17-OHCS, one, two, four and six hours after cortisol infusion were 82.2, 63.2, 38.3 and 23.5 μg/dl, respectriely, on an average of seven cases with adrenal insufficiency. The C<SUB>0</SUB> of plasma free 17-OHCS, the half-life of plasma free 17-OHCS and the ADV of 17-OHCS were 110.0 μg/dl, 100 body weight % and 185 minutes, respectively. Urinary total 17-OHCS, conjugated 17-OHCS, free 17-OHCS and 17-KGS excretion were 27.5, 20.0, 7.2 and 49.4% of administered cortisol, respectively, on an average of six cases with the intravenous infusion of 1 mg/Kg of cortisol only. In the oral administration of 40 mg of cortisol only, urinary total 17-OHCS, conjugated 17-OHCS, free 17-OHCS and 17-KGS excretion averaged 9.6, 8.8, 0.8 and 24.2 mg/day, respectively, in 9 cases. In the simultaneous intravenous infusion of 1 mg/Kg of cortisol and 50 units of ACTH, urinary total 17-OHCS, conjugated 17-OHCS,
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