Rohayem Julia, Drechsel Hendrik, Tittel Bettina, Hahn Gabriele, Pfaeffle Roland, Huebner Angela
Division of Paediatric Endocrinology and Diabetology, Children's Hospital, Technische Universität Dresden, Dresden, Germany.
Horm Res Paediatr. 2016;86(2):106-116. doi: 10.1159/000448098. Epub 2016 Aug 3.
Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966.
Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes.
The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients.
GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients.
GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology.
自1966年以来，生长激素（GH）一直用于治疗生长激素缺乏症（GHD）儿童。
采用回顾性和横断面相结合的方法，我们探讨了GHD患者的长期结局，分析了影响治疗反应的因素，确定了成年后的持续性，研究了垂体形态，并筛查了致病基因的突变。
回顾了96例GH缺乏儿童的病历。在50例患者的子集中，进行了成年后的重新评估，包括GHRH-精氨酸试验、垂体磁共振成像（MRI），以及对孤立性生长激素缺乏症（IGHD）患者的生长激素-1基因（GH1）和GHRH受体基因（GHRHR），以及多垂体激素缺乏症（MPHD）患者的HESX1、PROP1、POU1F1、LHX3、LHX4和GLI2进行突变筛查。
IGHD患者开始使用GH时的身高标准差分数（SDS）为-3.2±1.4，MPHD患者为-4.1±2.1。相对身高增长为0.3 SDS/年，绝对增长为1.6 SDS，IGHD/MPHD患者分别为1.2/2.6 SDS。77%的患者达到了父母平均靶身高。初始身高SDS、骨龄延迟和GH替代治疗时间与身高SDS增加相关。IGHD和MPHD患者分别有19%和89%的GHD持续至成年。在42例IGHD患者中有1例检测到GH1突变；在7例MPHD患者中有3例发现PROP1突变。垂体前叶发育不全，合并垂体后叶异位和MRI上垂体柄不可见，是MPHD患者的独特表现。
GH替代治疗成功纠正了GHD儿童的生长缺陷。虽然在大多数IGHD病例中遗传病因仍不明确，但PROP1突变是MPHD的主要原因。GHD持续至成年与垂体形态异常有关。
