Höybye Charlotte
Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm SE-171 76, Sweden.
Growth Horm IGF Res. 2004 Feb;14(1):1-15. doi: 10.1016/j.ghir.2003.09.003.
Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental retardation, short stature, abnormal body composition, muscular hypotonia and distinctive behavioural features. Excessive eating causes progressive obesity with increased cardiovascular morbidity and mortality. In the PWS genotype loss of one or more normally active paternal genes in region q11-13 on chromosome 15 is seen. It is supposed that the genetic alteration leads to dysfunction of several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common. PWS is well described in children, in whom GH treatment improves body composition, linear growth, physical strength and agility. Few studies have focused on adults. We examined a cohort of 19 young adults with clinical PWS (13 with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and nine patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and 8 women), subsequently completed a 12 months GH treatment trial, and GH had beneficial effects on body composition without significant adverse effects. The effects were more pronounced in the patients with the PWS genotype. Analysis of peptides involved in appetite regulation showed that leptin levels were high reflecting obesity and as a consequence NPY levels were low. In relation to the patients obesity circulating oxytocin levels were abnormally low and ghrelin levels abnormally high. Thus, oxytocin and ghrelin might be involved in the hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In conclusion this pilot study showed that adults with PWS have a partial GH deficiency, and GH treatment has beneficial effects on body composition in adult PWS without significant side-effects. Larger and longer term studies on the effect of GH replacement in adult PWS are encouraged.
普拉德-威利综合征（PWS）是一种遗传性疾病，其特征为轻度智力障碍、身材矮小、身体成分异常、肌张力低下以及独特的行为特征。过度进食会导致进行性肥胖，增加心血管疾病的发病率和死亡率。在PWS基因型中，可观察到15号染色体q11-13区域一个或多个正常活跃的父系基因缺失。据推测，这种基因改变会导致几个下丘脑中心功能障碍，生长激素（GH）缺乏（GHD）很常见。PWS在儿童中已有充分描述，对儿童进行GH治疗可改善身体成分、线性生长、体力和敏捷性。很少有研究关注成年人。我们研究了一组19名患有临床PWS的年轻成年人（13名基因型为阳性），平均体重指数为35kg/m²。基线时，GH-胰岛素样生长因子-I（IGF-I）系统的活性受损，GH值低，总IGF-I低，且由于肥胖，游离IGF-I和未被抑制的IGF结合蛋白-1（IGFBP-1）水平低。三分之二的患者性腺功能减退。骨密度（BMD）低。4名患者糖耐量受损，9名患者稳态模型评估（HOMA）指数高，表明存在胰岛素抵抗。7名患者有中度血脂异常。13名具有PWS基因型的患者身材较矮，IGF-I显著较低。17名患者（9名男性和8名女性）随后完成了为期12个月的GH治疗试验，GH对身体成分有有益影响，且无明显不良反应。这些影响在具有PWS基因型的患者中更为明显。对参与食欲调节的肽的分析表明，瘦素水平高反映了肥胖，因此神经肽Y（NPY）水平低。与患者的肥胖相关，循环催产素水平异常低，胃饥饿素水平异常高。因此，催产素和胃饥饿素可能与贪食有关。在GH治疗期间，NPY、瘦素和胃饥饿素没有变化。总之，这项初步研究表明，患有PWS的成年人存在部分GH缺乏，GH治疗对成年PWS患者的身体成分有有益影响，且无明显副作用。鼓励对成年PWS患者进行更大规模、更长期的GH替代治疗效果研究。
