11-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY AND GLUCOCORTICOID STATUS IN PATIENTS WITH ALCOHOLIC AND NONALCOHOLIC CHRONIC LIVER-DISEASE
11-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY AND GLUCOCORTICOID STATUS IN PATIENTS WITH ALCOHOLIC AND NONALCOHOLIC CHRONIC LIVER-DISEASE
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DOI：
10.1210/jc.76.3.748
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发表时间：
1993-03-01
影响因子：
5.8
通讯作者：
ELIAS, E
中科院分区：
文献类型：
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作者：
STEWART, PM;BURRA, P;ELIAS, E
11β -羟基类固醇脱氢酶（11betaHSD），主要存在于肝脏和肾脏，负责将活性皮质醇转化为可的松。这种穿梭机制的缺陷，例如在摄入甘草后，会导致尿中皮质醇[四氢皮质醇（THF）]与可的松[四氢可的松（the）]代谢物的比例增加。血浆皮质醇的半衰期延长，但浓度保持正常，因为伴随的皮质醇产量下降。酒精诱发的假性库欣综合征是一种病因不明的库欣综合征。由于许多记录的病例都有肝功能检查异常，我们研究了肝脏11β - ahsd活性异常是否可能在该疾病的发病机制中发挥作用。14例酒精性（ALD）慢性肝病患者和14例非酒精性（CLD）慢性肝病患者11β - ahsd明显缺乏[5 -THF + THF/THE: ALD， 1.94 +/- 0.38 (+/- sem)；与对照组相比，CLD为1.82 +/- 0.201 （0.94 +/- 0.04，P分别< 0.01和0.001）。在CLD组中，每日皮质醇生成率（通过主要皮质醇代谢物的总和来评估）适当降低[中位数，3,510；范围：1,101-8,940马克杯/24小时；对照组，5,492杯（范围，3,818-14,996）/24小时；P < 0.001]， 0900 h血浆皮质醇和尿游离皮质醇水平维持正常。然而，在ALD组中，皮质醇生成速率没有随之下降（皮质醇代谢物总和，5,043马克杯/24小时；范围，520-27,344）。结果，与CLD组（487 +/- 48 nmol/L, P < 0.05）和对照组（432 +/- 27 nmol/L, P < 0.001）相比，ALD组0900 h血浆皮质醇显著升高（633 +/- 52 nmol/L）。慢性ALD患者糖皮质激素过量的研究结果可能表明，酒精诱导的假性库欣综合征是在皮质醇代谢受损的情况下持续正常皮质醇分泌的结果。后者是由肝脏11betaHSD活性缺陷介导的；前者通过异常的糖皮质激素反馈或刺激下丘脑/垂体水平的皮质醇分泌。
11beta-Hydroxysteroid dehydrogenase (11betaHSD), found predominantly in liver and kidney, is responsible for the shuttling of active cortisol to cortisone. A defect in this shuttle mechanism, e.g. after liquorice ingestion, results in an increase in the ratio of urinary cortisol [tetrahydrocortisol (THF)] to cortisone [tetrahydrocortisone (THE)] metabolites. The plasma cortisol half-life is prolonged, but concentrations remain normal because of a concomitant fall in cortisol production.Alcohol-induced pseudo-Cushing's syndrome is an ill defined cause of Cushing's syndrome. Because many of the documented cases have abnormal liver function tests, we have investigated whether abnormal hepatic 11betaHSD activity may play a role in the pathogenesis of the condition.Fourteen patients with alcoholic (ALD) and 14 patients with non-alcoholic (CLD) chronic liver disease had marked deficiency of 11betaHSD [5a-THF + THF/THE: ALD, 1.94 +/- 0.38 (+/-SEM); CLD, 1.82 +/- 0.201 compared to controls (0.94 +/- 0.04; P < 0.01 and 0.001, respectively). In the CLD group, the daily cortisol production rate (as assessed by summation of principal cortisol metabolites) was reduced appropriately [median, 3,510; range, 1,101-8,940 mug/24 h; controls, 5,492 (range, 3,818-14,996) mug/24 h; P < 0.001], and normal 0900 h plasma cortisol and urinary free cortisol levels were maintained. However, in the ALD group, there was no concomitant fall in the cortisol production rate (sum of cortisol metabolites, 5,043 mug/24 h; range, 520-27,344). As a consequence, 0900 h plasma cortisol in the ALD group was significantly elevated (633 +/- 52 nmol/L) compared to values in the CLD group (487 +/- 48 nmol/L; P < 0.05) and controls (432 +/- 27 nmol/L; P < 0.001). Our findings of glucocorticoid excess in patients with chronic ALD may indicate that alcohol-induced pseudo-Cushing's syndrome develops as a result of continuing normal cortisol secretion in the face of impaired cortisol metabolism. The latter is mediated by defective hepatic 11betaHSD activity; the former by either abnormal glucocorticoid feedback or stimulation of cortisol secretion at the level of the hypothalamus/pituitary.