Berglund Agnethe, Gravholt Claus Højbjerg, Olsen Morten Smaerup, Christiansen Jens Sandahl, Stochholm Kirstine
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.
Department of Molecular Medicine, Aarhus University Hospital, Denmark.
Clin Endocrinol (Oxf). 2015 Nov;83(5):677-83. doi: 10.1111/cen.12848. Epub 2015 Aug 3.
Long-term safety of growth hormone (GH) treatment is an area of much debate. Studies including children treated with GH not only due to GHD, but also due to non-GHD causes like idiopathic short stature or like short stature in children born small for gestational age have suggested that GH treatment is associated with increased mortality or stroke.
To study the impact of GH replacement on overall and cause-specific mortality in childhood-onset GHD (CO GHD) patients.
A nationwide population-based registry study on patients with CO GHD and general population controls matched on age and gender. Mortality hazard ratios (HRs) were computed comparing patients and controls, and comparing GH-replaced patients and non-GH-replaced patients, using Cox regression. Comparing GH- and non-GH-replaced patients HRs were adjusted for birth year, year of diagnosis, gender, irradiation, ACTH insufficiency and primary disease.
A total of 494 patients with CO GHD each matched with 100 general population controls were included.
Mortality was substantially increased comparing patients with CO GHD and general population controls, HR = 7·51 (95% CI = 6·06-9·31). Comparing GH-replaced patients with non-GH-replaced patients mortality was significantly decreased in total (HR = 0·27, CI = 0·17-0·43) and due to malignancy (HR = 0·14, CI = 0·07-0·28) in GH-replaced patients. Adjusting for relevant confounders, this decrease remained significant both in total (HR = 0·56, CI = 0·32-0·96) and due to malignancy (HR = 0·33, CI = 0·16-0·69). Overall and cause-specific mortality was increased in both GH-replaced and non-GH-replaced patients compared to general population controls, but mortality was generally highest in non-GH-replaced patients.
The present data from a national cohort of patients with CO GHD do not support the suggestion that GH replacement is associated with increased mortality.
生长激素（GH）治疗的长期安全性是一个备受争议的领域。一些研究纳入了接受GH治疗的儿童，这些儿童不仅因生长激素缺乏症（GHD）接受治疗，还因特发性矮小或小于胎龄儿出生后的矮小等非GHD原因接受治疗，这些研究表明GH治疗与死亡率增加或中风有关。
研究GH替代治疗对儿童期起病的生长激素缺乏症（CO GHD）患者全因死亡率和特定病因死亡率的影响。
一项基于全国人口登记的研究，研究对象为CO GHD患者以及按年龄和性别匹配的普通人群对照。使用Cox回归计算患者与对照之间、GH替代治疗患者与未接受GH替代治疗患者之间的死亡风险比（HR）。比较接受GH治疗和未接受GH治疗的患者时，HR针对出生年份、诊断年份、性别、放疗、促肾上腺皮质激素（ACTH）缺乏和原发疾病进行了调整。
共纳入494例CO GHD患者，每组患者均与100名普通人群对照进行匹配。
与普通人群对照相比，CO GHD患者的死亡率大幅增加，HR = 7.51（95%置信区间[CI] = 6.06 - 9.31）。比较接受GH替代治疗的患者与未接受GH替代治疗的患者，总体死亡率显著降低（HR = 0.27，CI = 0.17 - 0.43），接受GH替代治疗的患者因恶性肿瘤导致的死亡率也显著降低（HR = 0.14，CI = 0.07 - 0.28）。在对相关混杂因素进行调整后，总体死亡率（HR = 0.56，CI = 0.32 - 0.96）和因恶性肿瘤导致的死亡率（HR = 0.33，CI = 0.16 - 0.69）仍显著降低。与普通人群对照相比，接受GH替代治疗和未接受GH替代治疗的患者全因死亡率和特定病因死亡率均有所增加，但未接受GH替代治疗的患者死亡率通常最高。
来自全国CO GHD患者队列的现有数据不支持GH替代治疗与死亡率增加相关的观点。
