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Cited by 35Pituitary Gland Disorders and TreatmentsThyroid Disorders and TreatmentsMetabolism and Genetic Disorders

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

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Naafs, J C, Verkerk, P H, Fliers, E, van Trotsenburg, A S P, Zwaveling-Soonawala, N·2020·European Journal of Endocrinology
DOI 10.1530/eje-20-0833
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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.

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  • In a previous study, 96% of patients with multiple pituitary hormone deficiencies had growth hormone deficiency and 88% had central adrenal insufficiency.

    “In our previous study 96% of patients with MPHD had growth hormone deficiency, and 88% had central adrenal insufficiency (11).”

    From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [11]

    The Discussion reports that 96% of MPHD patients had growth hormone deficiency. It reports ACTH deficiency—the relevant measure for central adrenal insufficiency—in 49 of 57 MPHD patients (86%), not 88%. The paper’s 88% figure refers to patients hospitalized before neonatal screening results became known. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • In that previous study, 95% of patients with early-detected central congenital hypothyroidism were diagnosed only after notification of an abnormal neonatal screening result.

    “Instead, 95% were diagnosed only after the notification of an abnormal neonatal screening result.”

    From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [11]

    The Early signs and symptoms section reports that 61 patients were hospitalized before screening results were known; among those patients, 95% were diagnosed only after the results were reported. The claim omits that hospitalized-subgroup qualifier and presents 95% as applying to all early-detected patients. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In a previous study of patients with early-detected central congenital hypothyroidism, the diagnosis was seldom made based on clinical signs, even though 66% had been hospitalized in the first week of life.

    “we found that the diagnosis was seldom made based on clinical signs, even though 66% of these patients had been hospitalized in the first week of life (11).”

    From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [11]

    The Results and Early signs and symptoms sections report that 61 of 92 patients (66%) were hospitalized before screening results were known, but only three were diagnosed on clinical grounds during those admissions. Our copy does not establish that all 61 hospitalizations occurred in the first week of life. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cites

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Authors
Naafs, J. C., Verkerk, P. H., Fliers, E., van Trotsenburg, A. S. P., & Zwaveling-Soonawala, N.
Affiliations
  • Emma Kinderziekenhuis (NL)
  • Netherlands Organisation for Applied Scientific Research (NL)
  • Amsterdam University Medical Centers (NL)
  • 1Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2020-12
Volume
183
Issue
6
Pages
627-636
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-20-0833
OpenAlex
W3089528973
Cited by
35
References
2
Citations by year
2026: 2 · 2025: 6 · 2024: 2 · 2023: 14 · 2022: 4 · 2021: 6 · 2020: 1
FWCI
4.73
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (acceptedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • TNO Repository (submittedVersion)
Funders
  • Pfizer (WI219179)
  • Amsterdam University Medical Centers
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
multiple pituitary hormone deficiency, newborn screening, pituitary stalk interruption syndrome, IGSF1, IRS4, genetic variants, diagnosis, pubertal stage, height
MeSH terms
Adolescent, Child, Child, Preschool, Congenital Hypothyroidism, Cross-Sectional Studies, Diagnostic Errors, Female, Humans, Hypopituitarism, Infant, Infant, Newborn, Male, Netherlands, Pituitary Hormones, Incidence, Neonatal Screening, Young Adult

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