中线脑缺陷中的内分泌疾病：视隔发育不良及相关疾病之间的差异。
Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders.
作者信息
Cerbone M, Güemes M, Wade A, Improda N, Dattani M
机构信息
London Centre for Paediatric Endocrinology and Diabetes at Great Ormond Street Children's Hospital and University College London Hospitals, London, UK.
Section of Molecular Basis of Rare Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Hospital Institute of Child Health, London, UK.
出版信息
EClinicalMedicine. 2020 Jan 9;19:100224. doi: 10.1016/j.eclinm.2019.11.017. eCollection 2020 Feb.
BACKGROUND
Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing.
METHODS
Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively.
FINDINGS
All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0·63(0·45,0·89) for GH, 0·48(0·34,0·69) for TSH, 0·55(0·38,0·80) for ACTH, 0·28(0·11,0·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2·27(0·88,5·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80·0% vs 41·6%, p<0·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4·2% (6/144) SOD and 3·2% (1/31) ONH, and only in patients with multisystem phenotypes.
INTERPRETATION
More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions.
FUNDING
M.C., M.G., and N.I. were supported by the European Society of Paediatric Endocrinology (ESPE) through ESPE Clinical Fellowships.
背景
视隔发育不良（SOD）是一种异质性先天性疾病。本研究的目的是调查一大群患有SOD、多种垂体激素缺乏（MPHD）和视神经发育不全（ONH）的儿童的临床表型，重点是内分泌检查。
方法
对患有SOD（n = 171）、MPHD（n = 53）和ONH（n = 35）的儿童进行回顾性单中心纵向研究。SOD+和SOD-分别表示患有或不患有垂体功能减退的患者。
研究结果
所有缺陷在MPHD中比SOD+更频繁且出现更早[生长激素（GH）的风险比（HR）：0·63（0·45，0·89），促甲状腺激素（TSH）的HR：0·48（0·34，0·69），促肾上腺皮质激素（ACTH）的HR：0·55（0·38，0·80），促性腺激素的HR：0·28（0·11，0·68）]，但尿崩症（DI）除外[HR：2·27（0·88，5·9）]。严重的下丘脑-垂体（H-P）异常在MPHD中更常见[80·0%对41·6%，异位垂体后叶（EPP）的p<0·0001]。垂体柄和垂体后叶异常与更严重的内分泌表型相关，并使SOD+的一个亚组有更早出现缺陷的风险。SOD和ONH具有从青春期延迟到早熟以及从消瘦到极度肥胖的异质性表型，而MPHD仅具有促性腺激素缺乏（GnD）和肥胖。在4·2%（6/144）的SOD和3·2%（1/31）的ONH中记录到死亡，且仅在具有多系统表型的患者中出现。
解读
SOD不仅仅是一种单一疾病，它代表了一系列涉及不同脑结构的畸形情况，其特征是内分泌具有动态和相继性。相比之下，MPHD表现出（主要）垂体前叶早发功能衰竭的更均匀表型。垂体柄和垂体后叶异常使SOD+的一个亚组有更高的早发缺陷风险。此外，SOD和MPHD队列在青春期进展方面存在显著差异。ONH和SOD之间的共同表型可能部分由共同的下丘脑功能障碍解释。队列之间的差异很重要，因为它们可能有助于通过决定更早的干预措施来规划管理并预防发病。
资金支持
M.C.、M.G.和N.I.得到了欧洲儿科内分泌学会（ESPE）通过ESPE临床奖学金的支持。
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