Bosch I Ara Laura, Katugampola Harshini, Dattani Mehul T
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.
Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Front Pediatr. 2021 Feb 2;8:600962. doi: 10.3389/fped.2020.600962. eCollection 2020.
Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism, and reproduction. The anterior pituitary produces and secretes growth hormone (GH), adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. The posterior pituitary hormone secretes antidiuretic hormone and oxytocin. The incidence is 1 in 4,000-1 in 10,000. The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 80-90% of CH cases remain unsolved in terms of molecular genetics. Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH including , and . Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation. Genotype-phenotype correlations are difficult to establish. There is a high phenotypic variability associated with different genetic mutations. The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies. Key investigations include MRI and baseline and dynamic pituitary function tests. However, dynamic tests of GH secretion cannot be performed in the neonatal period, and a diagnosis of GH deficiency may be based on auxology, MRI findings, and low growth factor concentrations. Once a hormone deficit is confirmed, hormone replacement should be started. If onset is acute with hypoglycaemia, cortisol deficiency should be excluded, and if identified this should be rapidly treated, as should TSH deficiency. This review aims to give an overview of CH including management of this complex condition.
先天性垂体功能减退症（CH）的特征是一种或多种垂体激素缺乏。垂体是生长、代谢和生殖的中枢调节器官。腺垂体产生并分泌生长激素（GH）、促肾上腺皮质激素、促甲状腺激素、促卵泡激素、黄体生成素和催乳素。神经垂体分泌抗利尿激素和催产素。发病率为1/4000至1/10000。大多数CH病例为散发性；然而，也发现了少数家族性病例。在后者中，经常能确定分子基础。在分子遗传学方面，80%至90%的CH病例仍未得到解决。几种转录因子和信号分子参与垂体的发育。这些基因中任何一个发生突变都可能导致CH，包括 ，以及 。在过去5年中，已经确定了几个与CH相关的新基因，但很可能还有许多基因有待确定，因为大多数CH患者没有已确定的突变。基因型与表型的相关性很难确立。不同的基因突变会导致高度的表型变异性。临床谱包括严重的中线发育障碍、垂体功能减退症（孤立性或与其他先天性异常合并）以及孤立性激素缺乏。关键检查包括MRI以及基线和动态垂体功能测试。然而，新生儿期无法进行GH分泌的动态测试，GH缺乏症的诊断可能基于体格检查、MRI结果和低生长因子浓度。一旦确认激素缺乏，就应开始激素替代治疗。如果发病伴有低血糖且病情急性发作，应排除皮质醇缺乏症，如确诊应迅速治疗，TSH缺乏症也应如此。本综述旨在概述CH，包括这种复杂病症的管理。
