al-Shoumer K A, Cox K H, Hughes C L, Richmond W, Johnston D G
Unit of Metabolic Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, United Kingdom.
J Clin Endocrinol Metab. 1997 Aug;82(8):2653-9. doi: 10.1210/jcem.82.8.4129.
Hypopituitary patients, particularly women, have excess mortality, mostly due to vascular disease. We have studied circulating lipid and lipoprotein concentrations, fasting and over 24 h, in hypopituitary women and men and in matched controls. Firstly, 67 hypopituitary patients (36 women) and 87 normal controls (54 women) were studied after an overnight fast. Secondly, 12 patients (6 women) and 14 matched controls (7 women) were studied over 24 h of normal meals and activity. The patients were all GH deficient and were replaced with cortisol, T4, and sex hormones where appropriate, but not with GH. In the first study, circulating triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were measured after an overnight fast. In the second study, fasting levels of apolipoprotein B, apolipoprotein A1, and lipoprotein(a) were also measured, and then circulating triglyceride and total cholesterol concentrations were measured over 24 h. Fasting concentrations of triglyceride (mean +/- SEM, 1.73 +/- 0.22 vs. 1.11 +/- 0.09 mmol/L; P = 0.0025), total cholesterol (6.45 +/- 0.25 vs. 5.59 +/- 0.21 mmol/L; P = 0.002), LDL cholesterol (4.58 +/- 0.24 vs. 3.80 +/- 0.19 mmol/L; P = 0.007), and apolipoprotein B (135 +/- 10 vs. 111 +/- 9 mg/dL; P = 0.048) were elevated in hypopituitary compared to control women. The lipid alterations were observed in older and younger women and occurred independently of sex hormone or glucocorticoid replacement. Fasting values were not significantly different in hypopituitary and control men. Patients and controls (women and men) had similar fasting HDL cholesterol, apolipoprotein A1, and lipoprotein(a) concentrations. Although the differences that existed in fasting lipid values were most marked in women, the men were also abnormal in this respect, in that a higher proportion of hypopituitary than control men had total and LDL cholesterol above recommended values (> or = 6.2 and > or = 4.1 mmol/L, respectively). In the postprandial period (0730-2030 h), the areas under the curve (AUC) for circulating triglyceride and total cholesterol were significantly higher in hypopituitary than control women (P = 0.0089 and P = 0.0016, respectively). The AUC for triglyceride and total cholesterol over 24 h were also significantly increased (P = 0.009 and P = 0.0004, respectively). No significant differences were observed for postprandial and 24-h AUC for triglyceride and total cholesterol concentrations in men. We conclude that hypopituitarism with conventional replacement therapy is associated with unfavorable fasting and postprandial lipid and lipoprotein concentrations, particularly in women. The changes may contribute to the observed increased vascular morbidity and mortality.
垂体功能减退患者，尤其是女性，死亡率过高，主要原因是血管疾病。我们研究了垂体功能减退的女性和男性以及相匹配的对照组在空腹及24小时期间的循环脂质和脂蛋白浓度。首先，对67例垂体功能减退患者（36名女性）和87名正常对照者（54名女性）进行了空腹研究。其次，对12例患者（6名女性）和14名相匹配的对照者（7名女性）进行了24小时正常饮食及日常活动状态下的研究。所有患者均存在生长激素缺乏，并在适当情况下接受皮质醇、T4和性激素替代治疗，但未使用生长激素。在第一项研究中，空腹过夜后测量循环甘油三酯、总胆固醇、高密度脂蛋白（HDL）胆固醇和低密度脂蛋白（LDL）胆固醇。在第二项研究中，还测量了空腹时载脂蛋白B、载脂蛋白A1和脂蛋白(a)的水平，然后在24小时内测量循环甘油三酯和总胆固醇浓度。与对照女性相比，垂体功能减退女性的空腹甘油三酯浓度（平均值±标准误，1.73±0.22 vs. 1.11±0.09 mmol/L；P = 0.0025）、总胆固醇浓度（6.45±0.25 vs. 5.59±0.21 mmol/L；P = 0.002）、LDL胆固醇浓度（4.58±0.24 vs. 3.80±0.19 mmol/L；P = 0.007）和载脂蛋白B浓度（135±10 vs. 111±9 mg/dL；P = 0.048）均升高。脂质改变在老年和年轻女性中均有观察到，且与性激素或糖皮质激素替代治疗无关。垂体功能减退男性和对照男性的空腹值无显著差异。患者和对照者（女性和男性）的空腹HDL胆固醇、载脂蛋白A1和脂蛋白(a)浓度相似。尽管空腹脂质值的差异在女性中最为明显，但男性在这方面也存在异常，即垂体功能减退男性中总胆固醇和LDL胆固醇高于推荐值（分别≥6.2和≥4.1 mmol/L）的比例高于对照男性。在餐后期间（0730 - 2030时），垂体功能减退女性循环甘油三酯和总胆固醇的曲线下面积（AUC）显著高于对照女性（分别为P = 0.0089和P = 0.0016）。24小时内甘油三酯和总胆固醇的AUC也显著增加（分别为P = 0.009和P = 0.0004）。男性餐后及24小时甘油三酯和总胆固醇浓度的AUC未观察到显著差异。我们得出结论，采用传统替代疗法的垂体功能减退与不良的空腹及餐后脂质和脂蛋白浓度相关，尤其是在女性中。这些变化可能导致所观察到的血管疾病发病率和死亡率增加。
