Binder Gerhard, Schnabel Dirk, Reinehr Thomas, Pfäffle Roland, Dörr Helmuth-Günther, Bettendorf Markus, Hauffa Berthold, Woelfle Joachim
University Children's Hospital, Pediatric Endocrinology, Hoppe-Seyler-Str. 1, 72076, Tübingen, Germany.
Center for Chronic Sick Children, Pediatric Endocrinology, Charité, University Medicine Berlin, Berlin, Germany.
Mol Cell Pediatr. 2020 Nov 3;7(1):16. doi: 10.1186/s40348-020-00108-2.
Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained.There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.
孤立性生长激素缺乏症（GHD）的定义为生长发育迟缓，同时伴有骨龄延迟、血清胰岛素样生长因子-1水平低下，以及在两项独立的生长激素刺激试验中生长激素峰值不足。先天性GHD可在任何年龄出现，并可能与垂体-下丘脑区域或脑中线的严重畸形有关。在极少数情况下，基因分析可揭示参与垂体和下丘脑胚胎发育的转录因子的种系突变。获得性GHD由辐射、炎症或肿瘤生长引起。与器质性GHD不同，特发性形式更为常见且病因不明。存在从孤立性GHD进展为垂体激素联合缺乏症的风险（整个群体中>5%），在患有器质性GHD的儿童中，尤其是垂体有严重畸形的儿童，这种风险明显增加。因此，在对孤立性GHD儿童进行随访时，通过临床和影像学观察以及内分泌基线检查来排除其他垂体激素缺乏症是明智的。与内分泌腺的原发性疾病不同，继发性缺乏症的临床表现通常较轻。垂体激素缺乏症可随时间从轻度不足发展为严重缺乏。本综述总结了目前关于最初诊断为孤立性GHD的儿童在rhGH治疗期间发生的其他垂体激素缺乏症的诊断和治疗的知识。尽管已知风险因素，但尚无绝对标准能够排除无进展为垂体激素联合缺乏症风险的儿童。对于患有器质性GHD的人，建议终身监测垂体的内分泌功能。本文是儿科内分泌学家研讨会的精华内容，他们筛选了文献，以获取有关最初孤立性GHD中不断演变的垂体缺陷及其诊断和治疗的证据。
