SYNDROME OF APPARENT MINERALOCORTICOID EXCESS - A DEFECT IN THE CORTISOL CORTISONE SHUTTLE
SYNDROME OF APPARENT MINERALOCORTICOID EXCESS - A DEFECT IN THE CORTISOL CORTISONE SHUTTLE
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DOI：
10.1172/jci113592
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发表时间：
1988-07-01
影响因子：
15.9
通讯作者：
EDWARDS, CRW
中科院分区：
文献类型：
--
作者：
STEWART, PM;CORRIE, JET;EDWARDS, CRW
本文报告首例成人11β-羟基类固醇脱氢酶缺乏症。皮质醇转化为皮质醇的障碍(由皮质醇和皮质醇代谢产物指示，不能将11α-[~H]皮质醇代谢为[~3H]H_2O)与高血压、低钾血症和肾素-血管紧张素-醛固酮系统抑制有关。当地塞米松建立在固定的Na+/K+摄入量的基础上时，口服地塞米松会产生钠尿和钾保留。血浆肾素活性变得可检测到。加入氢化可的松(S每日10 mg，连续4d)后，出现明显的Na+滞留、尿钾排泄(尿Na+/K+由1.2降至0.15)，血浆肾素活性受到抑制，血压升高。这些变化在没有接受治疗的受试者中也可以看到。皮质醇向皮质醇的转化不受影响。这些结果表明，在11β-OHSD缺乏症中，皮质醇是一种有效的矿质皮质激素。皮质醇氧化成皮质醇的主要部位是肾脏。在该患者中，11β-OHSD先天缺陷导致肾内皮质醇水平升高，继而作用于肾脏I型盐皮质激素受体。这种情况可以用地塞米松治疗，地塞米松会抑制皮质醇的分泌，并与II型糖皮质激素受体结合。我们认为11β-OHSD在决定I型受体的特异性中发挥着关键的旁分泌作用。在正常状态下，皮质醇被11β-OHSD转化为可的松，从而使醛固酮优先与肾脏和肠道中的I型受体结合。在这位患者中，缺乏11β-OHSD导致肾内皮质醇浓度升高，然后与I型受体结合。
The first adult case of 11.beta.-hydroxysteroid dehydrogenase (11.beta.-OHSD) deficiency is described. The impaired conversion of cortisol to cortisone (indicated by cortisol and cortisone metabolites and failure to metabolize 11.alpha.-[3H]cortisol to [3H]H2O), was associated with hypertension, hypokalemia, and suppression of the renin-angiotensin-aldosterone system. When established on a fixed Na+/K+ intake, dexamethasone, given orally, produced a natriuresis and potassium retention. Plasma renin activity became detectable. When hydrocortisone (10 mg daily s. c. for 4 d) was added, there was marked Na+ retention, a kaliuresis (urinary Na+/K+ falling from 1.2 to 0.15), with suppression of plasma renin activity and an increase in blood pressure. These changes were also seen with the subject on no treatment. Conversion of cortisone to cortisol was not affected. These results suggest that cortisol acts as a potent mineralocorticoid in 11.beta.-OHSD deficiency. The major site for the oxidation of cortisol to cortisone is the kidney. In this patient congenital deficiency of 11.beta.-OHSD results in high intrarenal cortisol levels which then act on renal type I mineralocorticoid receptors. This condition can be treated with dexamethsone, which suppresses cortisol secretion and binds to the type II glucocorticoid receptor. We suggest that 11.beta.-OHSD exerts a critical paracrine role in determining the specificity of the type I receptor. In the normal state cortisol is converted by 11.beta.-OHSD to cortisone which thus allows aldosterone to bind preferentially to the type I receptors in the kidney and gut. In this patient deficiency of 11.beta.-OHSD results in high intrarenal cortisol concentrations that then bind to the type I receptor.