J C Naafs1,2, P H Verkerk3, E Fliers2, A S P van Trotsenburg1, N Zwaveling-Soonawala1. 1. Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 2. Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam, The Netherlands. 3. TNO, Department of Child Health, Leiden, The Netherlands.
Abstract
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.
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.
Authors: Jolanda C Naafs; Jan Pieter Marchal; Eric Fliers; Paul H Verkerk; Michiel A J Luijten; Anita Boelen; A S Paul van Trotsenburg; Nitash Zwaveling-Soonawala Journal: J Clin Endocrinol Metab Date: 2021-03-08 Impact factor: 5.958
Authors: Konrad Patyra; Kristiina Makkonen; Maria Haanpää; Sinikka Karppinen; Liisa Viikari; Jorma Toppari; Mary Pat Reeve; Jukka Kero Journal: Front Endocrinol (Lausanne) Date: 2021-05-21 Impact factor: 5.555
Authors: Peter Lauffer; Nitash Zwaveling-Soonawala; Jolanda C Naafs; Anita Boelen; A S Paul van Trotsenburg Journal: Front Endocrinol (Lausanne) Date: 2021-09-09 Impact factor: 5.555