Walker B R, Campbell J C, Fraser R, Stewart P M, Edwards C R
University of Edinburgh, Department of Medicine, Western General Hospital, Scotland, UK.
Clin Endocrinol (Oxf). 1992 Dec;37(6):483-92. doi: 10.1111/j.1365-2265.1992.tb01478.x.
11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. We hypothesize that 11 beta-dehydrogenase is inhibited by ACTH, providing a mechanism whereby cortisol induces hypokalaemic alkalosis in ectopic ACTH syndrome.
DESIGN/MEASUREMENTS: The principal sources of plasma cortisone were assessed by selective venous catheterization with measurement of cortisol and cortisone by radioimmunoassays. The effect of ACTH on peripheral plasma cortisol/cortisone ratio was assessed in healthy volunteers during circadian rhythm, insulin induced hypoglycaemia, and infusions with exogenous ACTH or cortisol. In patients with Cushing's syndrome plasma cortisol/cortisone ratios were related to plasma potassium, corticosterone, and 11-deoxycorticosterone concentrations.
Catheterization was performed in 24 patients with valvular or ischaemic heart disease. Cushing's syndrome patients included: 15 with pituitary adenoma; two with adrenal adenoma; and nine with ectopic ACTH secretion.
Plasma cortisol/cortisone ratios were low in renal vein and high in hepatic vein. In healthy volunteers plasma cortisone increased during cortisol infusion but did not change with increases in endogenous or exogenous ACTH. Plasma cortisol/cortisone ratios were higher in ectopic ACTH syndrome than in other forms of Cushing's syndrome. However, the cortisol/cortisone ratio was no better a predictor of hypokalaemia than the levels of 11-deoxycorticosterone or corticosterone.
Peripheral conversion of cortisol to cortisone occurs mainly in the kidney and is inhibited by ACTH. In ectopic ACTH syndrome the characteristic mineralocorticoid excess can be accounted for by a combination of increased secretion of cortisol, corticosterone and of 11-deoxycorticosterone and decreased inactivation of cortisol and corticosterone by 11 beta-dehydrogenase.
11β-羟类固醇脱氢酶通过将皮质醇转化为无活性的可的松，保护肾脏盐皮质激素受体免受皮质醇影响。我们推测促肾上腺皮质激素（ACTH）可抑制11β-脱氢酶，这为皮质醇在异位ACTH综合征中诱导低钾性碱中毒提供了一种机制。
设计/测量：通过选择性静脉插管并采用放射免疫分析法测定皮质醇和可的松，评估血浆可的松的主要来源。在健康志愿者的昼夜节律、胰岛素诱导的低血糖以及外源性ACTH或皮质醇输注期间，评估ACTH对外周血浆皮质醇/可的松比值的影响。在库欣综合征患者中，血浆皮质醇/可的松比值与血浆钾、皮质酮和11-脱氧皮质酮浓度相关。
对24例瓣膜性或缺血性心脏病患者进行了插管。库欣综合征患者包括：15例垂体腺瘤患者；2例肾上腺腺瘤患者；9例异位ACTH分泌患者。
肾静脉中血浆皮质醇/可的松比值较低，肝静脉中较高。在健康志愿者中，输注皮质醇期间血浆可的松增加，但内源性或外源性ACTH增加时其无变化。异位ACTH综合征患者的血浆皮质醇/可的松比值高于其他形式的库欣综合征。然而，皮质醇/可的松比值在预测低钾血症方面并不比11-脱氧皮质酮或皮质酮水平更好。
皮质醇在外周转化为可的松主要发生在肾脏，且受ACTH抑制。在异位ACTH综合征中，特征性的盐皮质激素过多可由皮质醇、皮质酮和11-脱氧皮质酮分泌增加以及11β-脱氢酶对皮质醇和皮质酮的失活作用降低共同导致。
