Johnston D G, Alberti K G, Nattrass M, Barnes A J, Bloom S R, Joplin G F
Metabolism. 1980 Oct;29(11):1046-52. doi: 10.1016/0026-0495(80)90215-2.
Hormone and metabolite profiles were investigated over a 12-hr period in six patients with Cushing's syndrome, ten age- and sex-matched normal controls, and six moderately obese subjects matched for weight with the patient group. Mean diurnal plasma cortisol levels were 563 +/- 74 nmole/liter in the patients, 275 +/- 22 nmole/liter in normal controls and 241 +/- 32 nmole/liter in obese subjects, with total loss of diurnal changes in Cushing's syndrome. Fasting blood glucose concentration was similar in all groups although mild hyperglycemia occurred after meals in the Cushing's patients compared with normal and obese subjects (mean 12-hr blood glucose: Cushing's 6.31 +/- 0.39 mmole/liter; normal controls, 5.32 +/- 0.14 mmole/liter, p < 0.01; obese subjects, 5.41 +/- 0.18 mmole/liter, p < 0.05) despite marked hyperinsulinemia (mean 12-hr serum insulin: Cushing's 57.3 +/- 18.2 mU/liter; normal controls, 19.7 +/- 2.5 mU/liter, p < 0.02; obese subjects, 18.1 +/- 4.0 mU/liter, p < 0.05). Concentrations of the gluconeogenic precursors lactate, pyruvate, and alanine were raised in Cushing's syndrome, particularly postprandially. Plasma nonesterified fatty acids (NEFA), blood glycerol, and blood ketone body concentrations were comparable in all three groups although the normal diurnal variation in circulating NEFA and ketone body levels was lost in Cushing's syndrome. Serum triglyceride (TG) concentrations were grossly elevated in the Cushing's patients (mean 12-hr serum TG: Cushing's 3.51 +/- 1.23 mmole/liter; normal controls 0.89 +/- 0.19 mmole/liter, p < 0.02; obese subjects, 0.93 +/- 0.23 mmole/liter, p < 0.05) and correlated positively with serum insulin levels. Plasma glucagon concentrations were raised in Cushing's syndrome (mean 12-hr plasma glucagon: Cushing's 23.2 +/- 3.7 pmole/liter; normal controls 12.3 +/- 1.5 pmole/liter p < 0.01; obese subjects 12.2 +/0 2.0 pmole/liter, p < 0.02) and correlated positively with the serum cortisol but not with blood alanine, suggesting that some stimulatory factor other than alanine was responsible. The metabolic effects of chronic glucocorticoid excess thus may not be explained on the basis of obesity alone. Compensatory hyperinsulinemia limits the disturbance of carbohydrate and lipid metabolism in Cushing's syndrome but may be important in production of the hypertriglyceridemia observed.
在12小时期间，对6例库欣综合征患者、10例年龄和性别匹配的正常对照者以及6例体重与患者组匹配的中度肥胖受试者的激素和代谢物谱进行了研究。患者的日间血浆皮质醇平均水平为563±74纳摩尔/升，正常对照者为275±22纳摩尔/升，肥胖受试者为241±32纳摩尔/升，库欣综合征患者的日间变化完全消失。所有组的空腹血糖浓度相似，尽管与正常和肥胖受试者相比，库欣综合征患者餐后出现轻度高血糖（平均12小时血糖：库欣综合征患者6.31±0.39毫摩尔/升；正常对照者5.32±0.14毫摩尔/升，p<0.01；肥胖受试者5.41±0.18毫摩尔/升，p<0.05），尽管存在明显的高胰岛素血症（平均12小时血清胰岛素：库欣综合征患者57.3±18.2毫国际单位/升；正常对照者19.7±2.5毫国际单位/升，p<0.02；肥胖受试者18.1±4.0毫国际单位/升，p<0.05）。糖异生前体乳酸、丙酮酸和丙氨酸的浓度在库欣综合征中升高，尤其是餐后。所有三组的血浆非酯化脂肪酸（NEFA）、血甘油和血酮体浓度相当，尽管库欣综合征患者循环中NEFA和酮体水平的正常日间变化消失。库欣综合征患者的血清甘油三酯（TG）浓度显著升高（平均12小时血清TG：库欣综合征患者3.51±1.23毫摩尔/升；正常对照者0.89±0.19毫摩尔/升，p<0.02；肥胖受试者0.93±0.23毫摩尔/升，p<0.05），且与血清胰岛素水平呈正相关。库欣综合征患者的血浆胰高血糖素浓度升高（平均12小时血浆胰高血糖素：库欣综合征患者23.2±3.7皮摩尔/升；正常对照者12.3±1.5皮摩尔/升，p<0.01；肥胖受试者12.2±2.0皮摩尔/升，p<0.02），且与血清皮质醇呈正相关，但与血丙氨酸无关, 这表明除丙氨酸外还有其他刺激因素起作用。因此，慢性糖皮质激素过量的代谢作用可能不能仅基于肥胖来解释。代偿性高胰岛素血症限制了库欣综合征中碳水化合物和脂质代谢的紊乱，但可能在观察到的高甘油三酯血症的产生中起重要作用。
