Stewart P M, Walker B R, Holder G, O'Halloran D, Shackleton C H
Department of Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom.
J Clin Endocrinol Metab. 1995 Dec;80(12):3617-20. doi: 10.1210/jcem.80.12.8530609.
A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.
异位促肾上腺皮质激素（ACTH）综合征的一个特征性表现是盐皮质激素过多状态，尽管其病因仍不清楚。某些形式的内分泌性高血压，如摄入甘草，已被解释为在11β-羟类固醇脱氢酶（11βHSD）抑制或缺乏的情况下，皮质醇发挥了盐皮质激素的作用。该酶负责将皮质醇（F）转化为无激素活性的可的松，其体内活性可通过四氢皮质醇（THF）及其异构体（5αTHF）与四氢可的松的尿排泄率之比来推断。对22例库欣综合征患者（11例垂体依赖性、9例异位性和2例肾上腺腺瘤）和13名对照者进行了研究。与对照者相比，库欣综合征患者F的所有主要代谢产物排泄量显著增加（P<0.001），这是由于皮质醇分泌率增加了5至6倍所致[库欣综合征患者中位数为34.0（范围13.3 - 327）mg/天，对照者为6.1（范围2.5 - 10.3）mg/天]。无论病因如何，库欣综合征患者的THF加5αTHF/四氢可的松比值均显著升高[库欣综合征患者平均值为1.81（范围1.09 - 9.99），对照者为0.81（范围0.51 - 1.47）；P<0.001]，表明11βHSD活性存在缺陷。此外，与垂体依赖性库欣综合征患者相比，异位ACTH综合征患者的该比值显著更高（4.12对1.49；P<0.01），且与血清钾水平呈负相关（r = -0.57；P = 0.01；n = 22）。异位ACTH综合征盐皮质激素过多状态的一种解释似乎是，皮质醇因1于1βHSD正常代谢失败而不恰当地作用于盐皮质激素受体。11βHSD活性缺陷的原因尚不清楚，但可能是由于底物饱和、其他肾上腺类固醇的抑制或产物抑制所致。
