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.

中文翻译：

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主要孤立性 GHD 中不断发展的垂体激素缺陷：综述和专家共识

孤立性生长激素缺乏症 (GHD) 的定义是生长衰竭、骨龄延迟、血清胰岛素样生长因子-1 低以及两项独立的 GH 刺激试验中的 GH 峰值不足。先天性 GHD 可以出现在任何年龄，并且可能与垂体-下丘脑区域或大脑中线的显着畸形有关。在极少数情况下，遗传分析揭示了参与垂体和下丘脑胚胎发生的转录因子的种系突变。获得性 GHD 是由辐射、炎症或肿瘤生长引起的。与器质性 GHD 相比，特发性形式更常见且无法解释。存在从孤立性 GHD 发展为联合垂体激素缺乏症的风险（总组 > 5%），这在器质性 GHD 儿童中明显增加，特别是垂体显着畸形。因此，通过临床和放射学观察以及内分泌基线测试，在对孤立性 GHD 儿童的随访中排除额外的垂体激素缺乏是明智的。与内分泌腺的原发性疾病相比，继发性缺乏的临床表现通常较轻。垂体激素缺乏会随着时间的推移从轻度不足发展为严重缺乏。本综述总结了目前诊断和治疗初始诊断为孤立性 GHD 的儿童在 rhGH 治疗期间发生的额外垂体激素缺陷的知识。虽然已知危险因素，没有绝对标准可以排除没有任何进展为联合垂体激素缺乏症风险的儿童。建议对患有器质性 GHD 的人终身监测垂体的内分泌功能。这篇论文是儿科内分泌学家研讨会的精髓，他们筛选了有关最初孤立的 GHD 中不断发展的垂体缺陷及其诊断和治疗的证据的文献。