Verhelst Johan, Kendall-Taylor Pat, Erfurth Eva Marie, Price David Anthony, Geffner Mitchell, Koltowska-Häggström Maria, Jönsson Peter J, Wilton Patrick, Abs Roger
General Hospital Middleheim, Antwerp, Belgium.
J Clin Endocrinol Metab. 2005 Aug;90(8):4636-43. doi: 10.1210/jc.2005-0185. Epub 2005 May 31.
In epidemiological studies, hypopituitary adults show increased mortality compared with population controls. Patients with hypopituitarism caused by a craniopharyngioma (CP) and/or its treatment have a higher mortality than patients with other etiologies, such as a nonfunctioning pituitary adenoma (NFPA). To analyze this difference, we used the KIMS database (Pfizer International Metabolic Database) comparing CP and NFPA patients in terms of baseline characteristics and responses to GH replacement.
Baseline characteristics were studied in 351 CP patients (189 men and 162 women; mean age, 42.5 yr) and compared with 370 NFPA patients, matched for age and sex (185 men and 185 women; mean age, 42.5 yr). The effects of 2 yr of GH replacement were analyzed in a subgroup of 183 CP and 209 NFPA patients.
At baseline, both CP and NFPA patients had characteristic features of GH deficiency, with low serum IGF-I, increased body fat, dyslipidemia, and reduced quality of life. Male CP patients were significantly more obese (30.0 vs. 28.2 kg/m2; P = 0.0003) compared with NFPA patients, had a higher waist/hip ratio (P = 0.004), higher triglycerides (P = 0.003), and lower high-density lipoprotein cholesterol (P = 0.03). Similar, but much smaller, differences were seen in female CP compared with NFPA patients, only reaching significance for waist/hip ratio (P = 0.05) and triglycerides (P = 0.0004). CP patients had more often undergone surgery by the transcranial route (68.8% vs. 30.9%; P < 0.0001), and panhypopituitarism was more prevalent in CP than in NFPA patients (58.7% vs. 19.8%; P < 0.0001). The incidence of previous fractures, hypertension, coronary heart disease, claudication, and diabetes mellitus was high, but not different, between CP and NFPA patients. After 2 yr of GH replacement therapy, similar significant improvements were evident in both groups in fat-free mass, total and low-density lipoprotein cholesterol, and Quality-of-Life-Assessment in GH Deficient Adults score compared with baseline. In contrast to NFPA patients, CP patients had no significant decrease in body fat with GH therapy.
In the KIMS database, patients with CP have more often undergone surgery by the transcranial route than patients with NFPA, have a higher prevalence of pituitary deficiencies, are more obese (predominantly males), and have more dyslipidemia. This could provide an explanation, at least in part, for the higher mortality rate in CP patients observed in epidemiological studies. CP patients respond equally well to GH therapy in fat-free mass, lipids, and quality of life, but are less likely to lose body fat. We assume that this difference in response merely reflects the stronger tendency of CP patients to accumulate fat over time.
在流行病学研究中,与人群对照相比,垂体功能减退的成年人死亡率升高。由颅咽管瘤(CP)和/或其治疗引起的垂体功能减退患者的死亡率高于其他病因的患者,如无功能垂体腺瘤(NFPA)。为分析这种差异,我们使用KIMS数据库(辉瑞国际代谢数据库),比较CP和NFPA患者的基线特征及对生长激素(GH)替代治疗的反应。
研究了351例CP患者(189例男性和162例女性;平均年龄42.5岁)的基线特征,并与370例年龄和性别匹配的NFPA患者(185例男性和185例女性;平均年龄42.5岁)进行比较。在183例CP患者和209例NFPA患者的亚组中分析了2年GH替代治疗的效果。
基线时,CP和NFPA患者均有GH缺乏的特征,血清胰岛素样生长因子-I(IGF-I)水平低、体脂增加、血脂异常和生活质量下降。与NFPA患者相比,男性CP患者明显更肥胖(30.0 vs. 28.2 kg/m2;P = 0.0003),腰臀比更高(P = 0.004),甘油三酯更高(P = 0.003),高密度脂蛋白胆固醇更低(P = 0.03)。与NFPA患者相比,女性CP患者也有类似但小得多的差异,仅腰臀比(P = 0.05)和甘油三酯(P = 0.0004)达到显著水平。CP患者经颅手术的比例更高(68.8% vs. 30.9%;P < 0.0001),全垂体功能减退在CP患者中的患病率高于NFPA患者(58.7% vs. 19.8%;P < 0.0001)。CP和NFPA患者既往骨折、高血压、冠心病、跛行和糖尿病的发生率均较高,但无差异。GH替代治疗2年后,两组的去脂体重、总胆固醇和低密度脂蛋白胆固醇以及成人GH缺乏症生活质量评估评分与基线相比均有类似的显著改善。与NFPA患者不同,CP患者接受GH治疗后体脂无显著下降。
在KIMS数据库中,CP患者经颅手术的比例高于NFPA患者,垂体功能减退的患病率更高,更肥胖(主要是男性),血脂异常更严重。这至少可以部分解释在流行病学研究中观察到的CP患者较高的死亡率。CP患者在去脂体重、血脂和生活质量方面对GH治疗的反应同样良好,但体脂减少的可能性较小。我们认为这种反应差异仅仅反映了CP患者随时间积累脂肪的更强倾向。