Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening.

OBJECTIVE: 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). DESIGN: Nationwide, cross-sectional study. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data.

Objective: To provide an overview of cognitive and motor outcome, and quality of life (QoL) in patients with congenital central hypothyroidism (CH-C). Design: Systematic review with individual patient data (IPD) meta-analysis. Methods: OVID MEDLINE, EMBASE and PsycInfo were searched from inception to June 11th, 2019. Studies in patients with CH-C, either isolated or with multiple pituitary hormone deficiency (MPHD), were included if CH-C patients could be separated from any additional patient groups. Primary outcomes were full-scale intelligence quotient (FSIQ) and motor outcome; secondary outcome was QoL. Following data-extraction, one-stage IPD meta-analysis was performed, fitting a linear mixed model with FSIQ as dependent variable. Random intercepts were fitted for each study. Results: Six studies measuring FSIQ were eligible for meta-analysis, comprising 30 CH-C patients (20 males; 27 MPHD patients). FSIQ range was wide (64-123). Mean weighted FSIQ was 97 (95% CI: 88-105). Twenty-seven percent had an FSIQ below 85 (≥1 s.d. below norm score), and 10% below 70 (≥2 s.d. below norm score). There was no significant association between FSIQ and sex or age. Age at treatment initiation was available from three studies only, thus impeding a reliable analysis of this parameter. Motor outcome and QoL were each studied in one study; no quantitative analyses could be performed for these outcomes. Conclusion: A wide range in FSIQ scores was observed in CH-C patients. Results should be interpreted with caution, because included patients mainly had MPHD and age at treatment initiation was unknown for the majority of patients.

[A neonate with a mass on the upper back]. / Een neonaat met een zwelling op de rug.

Immediately after birth, a skin-covered mass with weak consistency was noted on the back of a full-term newborn boy. Ultrasound and MRI (performed to exclude spina bifida occulta) showed a multicystic venolymphatic malformation. Sclerotherapy or surgical excision are possible treatments. In asymptomatic patients, however, a watchful waiting approach is used.