Ayuk J, Clayton R N, Holder G, Sheppard M C, Stewart P M, Bates A S
Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, United Kingdom.
J Clin Endocrinol Metab. 2004 Apr;89(4):1613-7. doi: 10.1210/jc.2003-031584.
Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF-I remain uncertain. The West Midlands Pituitary database contains details of 419 patients (241 female) with acromegaly. Serum IGF-I data from the Regional Endocrine Laboratory were available for 360 patients (86%). At diagnosis, mean age was 47 yr (range, 12-84) and mean duration of follow-up was 13 yr (0.5-48). Sixty-one percent were treated by surgery and 39% by nonsurgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths. At the date of analysis (31 December 2001), 95 of the 419 patients had died (43 males), giving a standardized mortality ratio of 1.26 [confidence interval (CI), 1.03-1.54; P = 0.046]. After controlling for age and sex, data indicated that mortality was increased in subjects with posttreatment GH levels more than 2 micro g/liter, compared with those with levels less than 2 micro g/liter [ratio of mortality rates (RR), 1.55 (range, 0.97-2.50); P = 0.068]. By contrast, a much smaller increase was observed for subjects with elevated posttreatment IGF-I levels compared with those with normal levels [RR, 1.20 (range, 0.71-2.03); P = 0.50]. Treatment with radiotherapy was associated with increased mortality [RR, 1.67 (range, 1.09-2.56); P = 0.018], with cerebrovascular disease the predominant cause of death [standardized mortality ratio, 4.42 (range, 2.71-7.22); P = 0.005]. These results confirm the increased mortality in acromegaly and suggest that reduction of GH levels to less than 2 micro g/liter is beneficial in terms of improving long-term outcome. The sole use of IGF-I as a marker for effective treatment of acromegaly is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy.
多项回顾性研究已证实肢端肥大症患者死亡率增加，但致病因素以及与血清胰岛素样生长因子-I（IGF-I）的关系仍不明确。西米德兰兹郡垂体数据库包含419例肢端肥大症患者（241例女性）的详细信息。区域内分泌实验室提供了360例患者（86%）的血清IGF-I数据。诊断时，平均年龄为47岁（范围12 - 84岁），平均随访时间为13年（0.5 - 48年）。61%的患者接受手术治疗，39%接受非手术治疗。50%的患者单独使用放疗或作为辅助治疗。所有患者均在国家统计局登记以获取死亡信息。在分析日期（2001年12月31日），419例患者中有95例死亡（43例男性），标准化死亡率为1.26 [置信区间（CI），1.03 - 1.54；P = 0.046]。在控制年龄和性别后，数据表明，治疗后生长激素（GH）水平高于2μg/升的患者死亡率高于水平低于2μg/升的患者[死亡率比值（RR），1.55（范围0.97 - 2.50）；P = 0.068]。相比之下，治疗后IGF-I水平升高的患者与正常水平患者相比，死亡率升高幅度小得多[RR，1.20（范围0.71 - 2.03）；P = 0.50]。放疗与死亡率增加相关[RR，1.67（范围1.09 - 2.56）；P = 0.018]，脑血管疾病是主要死因[标准化死亡率，4.42（范围2.71 - 7.22）；P = 0.005]。这些结果证实了肢端肥大症患者死亡率增加，并表明将GH水平降至低于2μg/升对改善长期预后有益。该数据表明仅将IGF-I用作肢端肥大症有效治疗的标志物是不合理的。本研究还强调了放疗的潜在有害影响。
