Abs R, Bengtsson B A, Hernberg-Stâhl E, Monson J P, Tauber J P, Wilton P, Wüster C
Department of Endocrinology, University Hospital, Antwerp, Belgium.
Clin Endocrinol (Oxf). 1999 Jun;50(6):703-13. doi: 10.1046/j.1365-2265.1999.00695.x.
Long-term experience of growth hormone (GH) replacement therapy in a large population of hypopituitary adults with GH deficiency (GHD) is limited, and safety surveillance is clearly essential. KIMS, the Pharmacia & Upjohn International Metabolic Database, is a long-term, open, outcomes research programme of hypopituitary adult patients with GHD who are treated in a conventional clinical setting.
The present analysis encompasses data from 1034 hypopituitary adult GHD patients treated with GH for a total of 818 patient years.
Prior to GH therapy, the KIMS patient population exhibited an increased prevalence of obesity, diabetes mellitus (in females) and hyperlipidaemia, compared with normal populations described in published studies. Quality of life, assessed using a disease-specific questionnaire (QoL-AGHDA), was also reduced in KIMS patients. The maintenance dose of GH was significantly higher in patients who were receiving GH prior to enrolment into KIMS (non-naive patients) compared with patients who commenced GH at the time of enrolment (naive patients). In addition, dose of GH correlated significantly with body weight in the former group of patients. Analysis of serum levels of IGF-I indicated that overtreatment with GH was markedly more common in non-naive than in naive patients. The frequency of adverse events in KIMS patients was no higher than that reported in patients receiving placebo in previous clinical trials. Recurrence of pituitary or CNS tumours was reported in six patients, a rate consistent with data from control series. Three deaths were reported, none of which was obviously associated with GH treatment.
Our data, drawn from a large population of hypopituitary adults treated with GH for a total of more than 800 patient years, confirm previous reports that untreated GHD in hypopituitary adults is associated with a number of important clinical problems. In addition, the results suggest that there has been a shift in recent years from determination of GH dose on the basis of body weight to dose titration of individual patients, and indicate that the latter technique has important advantages. The data provide further evidence that GH replacement therapy is well-tolerated in adults. However, it is possible that some adverse events may not become evident over the time scale covered by the present analysis, and continued surveillance therefore remains mandatory.
在大量垂体功能减退的成年生长激素缺乏（GHD）患者中，生长激素（GH）替代疗法的长期经验有限，安全监测显然至关重要。KIMS（法玛西亚与普强国际代谢数据库）是一项针对在传统临床环境中接受治疗的垂体功能减退成年GHD患者的长期、开放的结局研究项目。
本分析涵盖了1034例垂体功能减退成年GHD患者的数据，这些患者接受GH治疗的总时长为818患者年。
与已发表研究中描述的正常人群相比，在接受GH治疗之前，KIMS患者群体中肥胖、糖尿病（女性）和高脂血症的患病率有所增加。使用特定疾病问卷（QoL-AGHDA）评估的生活质量在KIMS患者中也较低。与在入组KIMS时开始使用GH的患者（初治患者）相比，在入组KIMS之前就已接受GH治疗的患者（非初治患者）的GH维持剂量明显更高。此外，在前一组患者中，GH剂量与体重显著相关。对血清IGF-I水平的分析表明，非初治患者中GH过度治疗明显比初治患者更常见。KIMS患者不良事件的发生率不高于先前临床试验中接受安慰剂治疗患者报告的发生率。报告了6例垂体或中枢神经系统肿瘤复发，这一发生率与对照系列数据一致。报告了3例死亡，均未明显与GH治疗相关。
我们的数据来自大量接受GH治疗总时长超过800患者年的垂体功能减退成年患者，证实了先前的报告，即垂体功能减退成年患者中未经治疗的GHD与一些重要的临床问题相关。此外，结果表明近年来已从基于体重确定GH剂量转向对个体患者进行剂量滴定，并且表明后一种技术具有重要优势。数据进一步证明GH替代疗法在成年人中耐受性良好。然而，在本分析所涵盖的时间范围内，一些不良事件可能不明显，因此持续监测仍然必不可少。
