PDF(Pubmed)
Abstract：
BACKGROUND: NKX2-1-related disorders (NKX2-1-RD) are rare conditions affecting lung, thyroid, and brain development, primarily caused by pathogenic variants or deletions in the NKX2-1 gene. Congenital hypothyroidism (CH) is a common endocrine manifestation, leading to irreversible intellectual disability if left untreated.
OBJECTIVE: The aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD.
METHODS: This systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers.
RESULTS: Out of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging.
CONCLUSIONS: This review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.
OBJECTIVE: The aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD.
METHODS: This systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers.
RESULTS: Out of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging.
CONCLUSIONS: This review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.
摘要：
背景：NKX2-1相关疾病（NKX2-1-RD）是影响肺部的罕见疾病，甲状腺，和大脑发育，主要由NKX2-1基因的致病变异或缺失引起。先天性甲状腺功能减退症（CH）是一种常见的内分泌表现，如果不及时治疗会导致不可逆转的智力残疾。
目的：目的是评估目前使用筛查和诊断技术治疗NKX2-1-RD患者内分泌改变的证据。
方法：本系统综述按照PRISMA指南进行报道。以PICO格式提出了两个单独的研究问题，以涵盖NKX2-1-RD患者内分泌疾病的初步筛查和诊断程序。资格标准集中于具有疾病遗传确认和甲状腺功能减退症的患者。搜索了各种数据库，数据由两名评审员独立提取和评估.
结果：在1012项潜在相关研究中，包括46个，共113名患者。CH是最常见的内分泌改变（45％的患者）。根据血液TSH测量，只有21％的患者进行了新生儿筛查。TSH阈值在研究中差异很大，使甲减检测范围难以建立。使用血清TSH的诊断测试用于诊断甲状腺功能减退或确认其存在。35％的患者在新生儿年龄被诊断出，和42％在成人年龄。由于临床症状而确定的其他荷尔蒙功能障碍，比如垂体前叶缺乏,在以后的生活中被发现。甲状腺闪烁显像和超声检查可以描述30％的甲状腺功能减退病例的甲状腺。在具有相同变异的个体中观察到表型变异性，使基因型-表型相关性具有挑战性。
结论：这篇综述强调了NKX2-1-RD内分泌筛查标准方案的必要性，强调一致的方法和激素阈值水平的重要性。NKX2-1基因变体的变异进一步使诊断工作复杂化。未来的研究应集中在优化早期筛查方案和诊断策略上。
目的：目的是评估目前使用筛查和诊断技术治疗NKX2-1-RD患者内分泌改变的证据。
方法：本系统综述按照PRISMA指南进行报道。以PICO格式提出了两个单独的研究问题，以涵盖NKX2-1-RD患者内分泌疾病的初步筛查和诊断程序。资格标准集中于具有疾病遗传确认和甲状腺功能减退症的患者。搜索了各种数据库，数据由两名评审员独立提取和评估.
结果：在1012项潜在相关研究中，包括46个，共113名患者。CH是最常见的内分泌改变（45％的患者）。根据血液TSH测量，只有21％的患者进行了新生儿筛查。TSH阈值在研究中差异很大，使甲减检测范围难以建立。使用血清TSH的诊断测试用于诊断甲状腺功能减退或确认其存在。35％的患者在新生儿年龄被诊断出，和42％在成人年龄。由于临床症状而确定的其他荷尔蒙功能障碍，比如垂体前叶缺乏,在以后的生活中被发现。甲状腺闪烁显像和超声检查可以描述30％的甲状腺功能减退病例的甲状腺。在具有相同变异的个体中观察到表型变异性，使基因型-表型相关性具有挑战性。
结论：这篇综述强调了NKX2-1-RD内分泌筛查标准方案的必要性，强调一致的方法和激素阈值水平的重要性。NKX2-1基因变体的变异进一步使诊断工作复杂化。未来的研究应集中在优化早期筛查方案和诊断策略上。
