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普拉德-威利综合征:谁可以使用生长激素?

Prader-Willi syndrome: who can have growth hormone?

作者信息

Stafler P, Wallis C

机构信息

Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK.

出版信息

Arch Dis Child. 2008 Apr;93(4):341-5. doi: 10.1136/adc.2007.126334. Epub 2007 Dec 18.

Abstract

Growth hormone (GH) is licensed for treatment for Prader-Willi syndrome (PWS) for improvement of body composition,1(-)3 height velocity, mobility, behaviour and quality of life.4 Recent case reports, however, have pointed out the occurrence of sudden death during initiation of GH, mainly during sleep and possibly related to severe obesity and sleep-disordered breathing (SDB).5(-)15 Concerns for an increased mortality in PWS children starting GH therapy led to a call for cessation of its use. Children with PWS are at risk of developing SDB secondary to both deficient autonomic sleep control and upper airway obstruction (UAO). It has been suggested that GH exacerbates pre-existing gas-exchange deficiencies in three ways: (a) by stimulation of adenotonsillar hypertrophy;16 17 (b) by a rise in basal metabolic rate with a resultant rise in oxygen demand;18 and (c) by normalisation of previously decreased hydration with augmentation of volume load.19 Are we withholding GH therapy, a treatment known to be of benefit in PWS, without adequate evidence to justify our actions? We consider it safe to treat severely obese children with GH once SDB is addressed using respiratory support such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). In this paper, we evaluate the current evidence for the use of GH in PWS from a respiratory bias and propose a pathway for the identification and monitoring of these "at risk" patients.

摘要

生长激素(GH)已被批准用于治疗普拉德-威利综合征(PWS),以改善身体成分、身高增长速度、活动能力、行为和生活质量。然而,最近的病例报告指出,在开始使用GH期间会发生猝死,主要发生在睡眠期间,可能与严重肥胖和睡眠呼吸障碍(SDB)有关。对开始接受GH治疗的PWS儿童死亡率增加的担忧导致人们呼吁停止使用GH。PWS儿童由于自主睡眠控制不足和上气道阻塞(UAO)而有发生SDB的风险。有人提出,GH通过以下三种方式加剧先前存在的气体交换不足:(a)刺激腺样体扁桃体肥大;(b)基础代谢率升高,导致氧气需求增加;(c)使先前减少的水合作用正常化,同时增加容量负荷。我们是否在没有充分证据证明我们的行动合理的情况下,就停止使用已知对PWS有益的GH治疗呢?我们认为,一旦使用持续气道正压通气(CPAP)或双水平气道正压通气(BiPAP)等呼吸支持措施解决了SDB问题,就可以安全地用GH治疗重度肥胖儿童。在本文中,我们从呼吸角度评估目前在PWS中使用GH的证据,并提出一条识别和监测这些“高危”患者的途径。

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