Kornel L, Patel S K, Ezzeraimi E, Shackleton C H
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Steroids. 1995 Dec;60(12):817-23. doi: 10.1016/0039-128x(95)00141-c.
A method was developed for the estimation of levels of cortisol-21-sulfate (F KS), cortisone-21-sulfate (ES), and 20(alpha + beta)-reduced cortisol-21-sulfates in blood plasma. Levels of these conjugates were determined in peripheral vein plasma of 42 normal subjects, 21 men, and 21 women (age range 20-64 years) and in adrenal vein plasma of patients with various adrenocortical disorders, six patients with primary hyperaldosteronism, five patients with Cushing's syndrome, and in two obese patients, suspected to have Cushing's syndrome, but with inconclusive laboratory findings. Adrenal vein blood was obtained by percutaneous, trans-femoral adrenal vein catheterization. Levels of non-conjugated (free) cortisol were determined in all plasma samples along with those of the sulfated steroids. F kappa S was found in all plasma samples, both in men and women. The variation in F kappa S levels paralleled that in the free cortisol levels, thus the ratio of F kappa/F kappa S was the same in the blood samples drawn at 8 AM as in those drawn at 4 PM or 5 PM (ranges: 17.5-36.3 in men, 23.6-45.8 in women). The levels of F kappa S were relatively lower in women than in men (women 610-880 ng/100 mL at AM, 300-510 ng/100 mL at PM; men: 760-1,220 ng/100 mL at AM, 380-760 ng/100 mL at PM). Plasma levels of total sulfate-conjugated delta 4-3-keto-C-21 steroids (F kappa S + E kappa S + 20(alpha+beta)-dihydrocortisol-21-sulfates) were 30-40% higher than those of the levels of cortisol-21-sulfate alone (separated by thin-layer chromatography). In the adrenal vein plasma, levels of delta 4-3-keto-C-21-steroid-21-yl sulfates were 20 to 40 times higher than levels of these steroids in the peripheral blood. The bulk of the steroid sulfate measured in the adrenal vein plasma consisted of cortisol-21-sulfate. The ratio of F kappa/F kappa S in the adrenal vein plasma was markedly smaller than in the peripheral vein plasma; it was 6.9-12.3 in males and 4.9-6.7 in females, whereas in the peripheral vein of the same subjects it was 19.2-43.7 in males and 21.4-48.3 in females. Cortisol-21-sulfate isolated from adrenal vein plasma was identified by mass spectrometry. The data presented provide evidence for the secretion of this conjugate by the adrenal cortex. Its secretion appears to be markedly elevated in patients with Cushing's syndrome, both due to hyperplasia and due to adrenal adenoma, as compared with normal subjects and patients with primary aldosteronism, both males and females. However, the F kappa/F kappa S ratio was markedly lower in Cushing's patients due to adrenal adenoma than due to adrenal hyperplasia, this suggesting that ACTH is stimulating intra-adrenal hydrolysis of cortisol sulfate.
已开发出一种用于估算血浆中皮质醇 - 21 - 硫酸盐（F KS）、可的松 - 21 - 硫酸盐（ES）以及20（α + β）- 还原皮质醇 - 21 - 硫酸盐水平的方法。在42名正常受试者（21名男性和21名女性，年龄范围20 - 64岁）的外周静脉血浆以及患有各种肾上腺皮质疾病的患者的肾上腺静脉血浆中测定了这些共轭物的水平，其中包括6名原发性醛固酮增多症患者、5名库欣综合征患者，以及2名疑似患有库欣综合征但实验室检查结果不明确的肥胖患者。肾上腺静脉血通过经皮股静脉肾上腺静脉插管获取。在所有血浆样本中同时测定了非共轭（游离）皮质醇以及硫酸化类固醇的水平。在所有血浆样本中，无论男性还是女性，均检测到了F kappa S。F kappa S水平的变化与游离皮质醇水平的变化平行，因此上午8点采集的血样中F kappa/F kappa S的比值与下午4点或5点采集的血样中的比值相同（范围：男性为17.5 - 36.3，女性为23.6 - 45.8）。女性的F kappa S水平相对低于男性（上午女性为610 - 880 ng/100 mL，下午为300 - 510 ng/100 mL；男性上午为760 - 1220 ng/100 mL，下午为380 - 760 ng/100 mL）。通过薄层色谱法分离后，总硫酸化共轭δ4 - 3 - 酮 - C - 21类固醇（F kappa S + E kappa S + 20（α + β）- 二氢皮质醇 - 21 - 硫酸盐）的血浆水平比单独的皮质醇 - 21 - 硫酸盐水平高30 - 40%。在肾上腺静脉血浆中，δ4 - 3 - 酮 - C - 21 - 类固醇 - 21 - 基硫酸盐的水平比外周血中这些类固醇的水平高20至40倍。肾上腺静脉血浆中测得的类固醇硫酸盐大部分由皮质醇 - 21 - 硫酸盐组成。肾上腺静脉血浆中F kappa/F kappa S的比值明显小于外周静脉血浆中的比值；男性为6.9 - 12.3，女性为4.9 - 6.7，而在同一受试者的外周静脉中，男性为19.2 - 43.7，女性为21.4 - 48.3。通过质谱法鉴定了从肾上腺静脉血浆中分离出的皮质醇 - 21 - 硫酸盐。所呈现的数据为肾上腺皮质分泌这种共轭物提供了证据。与正常受试者以及原发性醛固酮增多症患者（无论男性还是女性）相比，在因增生和肾上腺腺瘤导致的库欣综合征患者中，其分泌似乎明显升高。然而，因肾上腺腺瘤导致的库欣综合征患者的F kappa/F kappa S比值明显低于因肾上腺增生导致的患者，这表明促肾上腺皮质激素正在刺激肾上腺内皮质醇硫酸盐的水解。
