Murray Philip G., Clayton Peter E.
Division of Developmental Biology and Medicine, School of Medical Sciences University of Manchester and Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, UK, M13 9WL.
Division of Developmental Biology and Medicine, School of Medical Sciences, University of Manchester and Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, UK, M13 9WL.
Growth is a fundamental process of childhood and growth disorders remain one of the commonest reasons for referral to a pediatric endocrinologist. Growth can be divided into four phases – fetal, infancy, childhood and the pubertal phase with different hormonal components influencing growth at each stage. The GH-IGF1 axis plays a major role in the childhood phase of growth with a significant role alongside sex steroids during puberty while in infancy thyroid hormone and nutrition are vital. Although an uncommon cause of short stature disorders of the GH-IGF1 axis are extremely important due to the effectiveness of recombinant human growth hormone therapy for the child with GH deficiency (GHD). Here we review the diagnosis of growth hormone deficiency through a combination of auxology, biochemistry, imaging, and genetic testing. Particular focus is given to the accuracy of IGF-1/BP3 for diagnosis as well as the known problems with GH stimulation tests and GH assays. Isolated GHD is caused by mutations in GH1, BTK, and RNPC3 while GHD seen as part of multiple pituitary hormone deficiency is known to be caused by mutations in a wide variety of genes. A variety of structural malformations of the brain can be associated with congenital GHD with the commonest being the presence of an ectopic posterior pituitary or Septo-optic dysplasia. Acquired GHD is rarer and caused by tumors, radiotherapy, hypophysitis, and traumatic brain injury. Treatment with recombinant human GH is highly efficacious in improving height in children with GH deficiency and extremely safe. Short stature disorders are, rarely, also caused by a variety of other disorders of the GH-IGF1 axis. Resistance to growth hormone is seen in Laron syndrome and in mutations in and while decreased bioavailability of IGF1 is seen in ALS deficiency and PAPPA2 deficiency. Treatment with recombinant human IGF1 (rhIGF1) is available for those with IGF-I deficiency caused by either Laron syndrome or mutations. rhIGF1 is effective in improving height but treatment is less effective than the use of GH to treat GH deficiency. The role of IGF1 in pre-natal growth is highlighted by the phenotype of patients with IGF1R or IGF1 mutations where pre-natal growth is commonly impaired and children born small for gestational age. GH excess is much rarer than GH deficiency in childhood and can be caused by pituitary adenomas, optic nerve gliomas (seen predominantly with NF1), McCune Albright syndrome, or Carney complex. Treatment is with surgery, somatostatin analogs, or GH receptor antagonists. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
生长是儿童期的一个基本过程，生长障碍仍然是转诊至儿科内分泌专家处最常见的原因之一。生长可分为四个阶段——胎儿期、婴儿期、儿童期和青春期，每个阶段有不同的激素成分影响生长。生长激素-胰岛素样生长因子1（GH-IGF1）轴在儿童期生长中起主要作用，在青春期与性类固醇一起发挥重要作用，而在婴儿期甲状腺激素和营养至关重要。尽管生长激素-胰岛素样生长因子1轴紊乱是身材矮小的罕见原因，但由于重组人生长激素疗法对生长激素缺乏（GHD）儿童有效，所以极其重要。在此，我们通过结合体格检查、生物化学、影像学和基因检测来综述生长激素缺乏症的诊断。特别关注IGF-1/BP3用于诊断的准确性以及生长激素刺激试验和生长激素测定中已知的问题。孤立性生长激素缺乏症由GH1、BTK和RNPC3基因突变引起，而作为多种垂体激素缺乏症一部分的生长激素缺乏症已知由多种基因突变引起。多种脑结构畸形可与先天性生长激素缺乏症相关，最常见的是存在异位垂体后叶或视隔发育不良。获得性生长激素缺乏症较为罕见，由肿瘤、放疗、垂体炎和创伤性脑损伤引起。用重组人生长激素治疗对改善生长激素缺乏症儿童的身高非常有效且极其安全。身材矮小障碍也很少由生长激素-胰岛素样生长因子1轴的多种其他紊乱引起。在拉伦综合征以及特定基因突变时可见生长激素抵抗，而在酸性不稳定亚基（ALS）缺乏症和妊娠相关血浆蛋白A2（PAPPA2）缺乏症中可见胰岛素样生长因子1（IGF1）的生物利用度降低。对于由拉伦综合征或特定基因突变引起的IGF-I缺乏症患者，可使用重组人IGF1（rhIGF1）进行治疗。rhIGF1在改善身高方面有效，但治疗效果不如使用生长激素治疗生长激素缺乏症。IGF1在产前生长中的作用通过IGF1受体（IGF1R）或IGF1基因突变患者的表型得到凸显，这些患者的产前生长通常受损，出生时为小于胎龄儿。儿童期生长激素过多比生长激素缺乏少见得多，可由垂体腺瘤、视神经胶质瘤（主要见于1型神经纤维瘤病（NF1））、McCune-Albright综合征或卡尼综合征引起。治疗方法为手术、生长抑素类似物或生长激素受体拮抗剂。欲全面涵盖内分泌学的所有相关领域，请访问我们的在线免费网络文本，网址为WWW.ENDOTEXT.ORG。
