Stewart P M, Burra P, Shackleton C H, Sheppard M C, Elias E
Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
J Clin Endocrinol Metab. 1993 Mar;76(3):748-51. doi: 10.1210/jcem.76.3.8445034.
11 beta-Hydroxysteroid dehydrogenase (11 beta HSD), 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 11 beta HSD 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 11 beta HSD [5 alpha-THF + THF/THE: ALD, 1.94 +/- 0.38 (+/- SEM); CLD, 1.82 +/- 0.20] 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 micrograms/24 h; controls, 5,492 (range, 3,818-14,996) micrograms/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 micrograms/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 11 beta HSD activity; the former by either abnormal glucocorticoid feedback or stimulation of cortisol secretion at the level of the hypothalamus/pituitary.
11β-羟类固醇脱氢酶（11βHSD）主要存在于肝脏和肾脏中，负责将活性皮质醇转化为可的松。这种转化机制的缺陷，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）]代谢产物的比例增加。血浆皮质醇半衰期延长，但由于皮质醇生成同时减少，其浓度仍保持正常。酒精性假性库欣综合征是库欣综合征的一个病因不明的情况。由于许多已记录的病例肝功能检查异常，我们研究了肝脏11βHSD活性异常是否可能在该病症的发病机制中起作用。与对照组（0.94±0.04；P分别<0.01和0.001）相比,14例酒精性肝病（ALD）患者和14例非酒精性肝病（CLD）患者的11βHSD明显缺乏[5α-THF+THF/THE：ALD，1.94±0.38（±标准误）；CLD，1.82±0.20]。在CLD组中，每日皮质醇生成率（通过主要皮质醇代谢产物总和评估）适当降低[中位数，3510；范围，1101 - 8940微克/24小时；对照组，5492（范围，3818 - 14996）微克/24小时；P<0.001]，并维持09:00时正常的血浆皮质醇和尿游离皮质醇水平。然而，在ALD组中，皮质醇生成率没有相应下降（皮质醇代谢产物总和，5043微克/24小时；范围，520 - 27344）。因此，ALD组09:00时的血浆皮质醇显著升高（633±52纳摩尔/升），与CLD组（487±48纳摩尔/升；P<0.05）和对照组（432±27纳摩尔/升；P<0.001）的值相比。我们在慢性ALD患者中发现糖皮质激素过多，这可能表明酒精性假性库欣综合征的发生是由于在皮质醇代谢受损的情况下，皮质醇持续正常分泌所致。后者由肝脏11βHSD活性缺陷介导；前者由异常的糖皮质激素反馈或下丘脑/垂体水平的皮质醇分泌刺激介导。
