Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam, The Netherlands.
Eur J Endocrinol. 2020 Dec;183(6):627-636. doi: 10.1530/EJE-20-0833.
To evaluate clinical characteristics of patients with central congenital hypothyroidism (CH), detected in the Dutch neonatal screening program. This included patients with isolated central CH but the majority have multiple pituitary hormone deficiencies (MPHD).
Nationwide, cross-sectional study.
Data was collected on clinical characteristics, endocrine tests and neuroimaging of central CH patients, detected by the Dutch neonatal screening and born between 1 January 1995 and 1 January 2015. Height and pubertal status were assessed during a study visit. Isolated central CH patients without a confirmed genetic diagnosis were offered genetic (re-)testing.
During the 20-year period 154 central CH patients were detected (incidence of permanent central CH 1:25 642). After excluding deceased (15), severe syndromic (7) and transient patients (6), 92 of 126 eligible patients were included (57 MPHD; 79% male). Sixty-one patients (50 MPHD) had been hospitalized before screening results were reported, but central CH was diagnosed on clinical grounds in only three of them (5%). MRI abnormalities consistent with pituitary stalk interruption syndrome were seen in 50 (93%) MPHD patients. Among isolated central CH patients, 27 (84%) had an IGSF1, TBL1X or IRS4 gene variant (53, 16 and 16%, respectively).
Many patients with central CH have neonatal health problems, especially MPHD patients. Despite hospital admission of two-thirds of patients, almost none were diagnosed clinically, but only after the notification of an abnormal screening result was received. This indicates that central CH, especially if isolated, is an easily missed clinical diagnosis.
评估在荷兰新生儿筛查计划中发现的中枢性先天性甲状腺功能减退症（CH）患者的临床特征。这包括孤立性中枢性 CH 患者，但大多数患者存在多种垂体激素缺乏症（MPHD）。
全国性的、横断面研究。
收集了在荷兰新生儿筛查中发现的中枢性 CH 患者的临床特征、内分泌检查和神经影像学数据，这些患者的出生时间在 1995 年 1 月 1 日至 2015 年 1 月 1 日之间。在研究访问期间评估了身高和青春期状态。对没有明确遗传诊断的孤立性中枢性 CH 患者提供遗传（重新）检测。
在 20 年期间，共发现 154 例中枢性 CH 患者（永久性中枢性 CH 的发病率为 1:25642）。排除死亡（15 例）、严重综合征（7 例）和短暂性患者（6 例）后，共有 126 例符合条件的患者中的 92 例被纳入（57 例 MPHD；男性占 79%）。61 例（50 例 MPHD）在报告筛查结果前已住院，但只有 3 例（5%）根据临床诊断为中枢性 CH。50 例（93%）MPHD 患者的 MRI 异常与垂体柄中断综合征一致。在孤立性中枢性 CH 患者中，有 27 例（84%）存在 IGSF1、TBL1X 或 IRS4 基因突变（分别为 53%、16%和 16%）。
许多中枢性 CH 患者存在新生儿健康问题，尤其是 MPHD 患者。尽管三分之二的患者住院，但几乎没有患者是根据临床诊断，而是在收到异常筛查结果通知后才被诊断。这表明中枢性 CH，尤其是孤立性中枢性 CH，是一种容易被忽视的临床诊断。
