The Severity of Congenital Hypothyroidism of Central Origin Should Not Be Underestimated
Open accessAbstract
CONTEXT: Congenital hypothyroidism (CH) may be of thyroidal (CHT) or central origin (CHC). Worldwide, most neonatal screening programs are TSH-based and effectively detect CHT. Only a few screening programs measure total or free T4 and TSH simultaneously or stepwise, enabling detection of CHT as well as CHC. A frequently used argument against screening for CHC is its presumed mild hypothyroid character. In the recently published European Society for Paediatric Endocrinology (ESPE) CH consensus guidelines on screening, diagnosis, and management, severity of CH is classified based on initial free T4 (FT4) concentrations. OBJECTIVE: Our objective was to assess disease severity of CHC compared with CHT in a Dutch cohort of CH patients. METHODS: Pretreatment FT4 concentrations were analyzed in all children with CH detected by the Dutch neonatal T4+TSH+T4-binding-globulin (TBG) screening between 1995 and 2011. Disease severity was classified using the FT4-based ESPE classification. RESULTS: Between 1995 and 2011, 1288 children were diagnosed with CH. Data of 1200 (143 CHC and 1057 CHT) were available for analysis. Based on FT4 concentrations, 4 children with CHC (2.8%) had severe, 75 (52.4%) moderate, and 64 (44.8%) mild CH. In the CHT group, 280 children (26.5%) had severe, 341 (32.3%) moderate, and 436 (41.2%) mild CH. CONCLUSION: Our results indicate that, based on initial FT4 values, severe CH was much more prevalent in CHT compared with CHC. However, CHC itself should not be considered as only mild because more than half of CHC patients have moderate CH with initial FT4 below 10 pmol/L (0.78 ng/dl).
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In congenital central hypothyroidism, a delayed onset of treatment causes irreversible neurological defects.
“In these cases, a delayed onset of treatment causes irreversible neurological defects.”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [3]
The Discussion (page unavailable) reports developmental delay in 19 of 34 children with late-diagnosed central congenital hypothyroidism and suggests that early treatment might have prevented some of it. It also says the cause is difficult to determine because other pituitary hormone deficiencies can cause brain damage. The paper does not establish that delayed treatment itself causes irreversible neurological defects. (LLM, conf=0.88)
Experimental — accuracy not yet measuredClinical detection of central congenital hypothyroidism usually occurs far beyond the neonatal period.
“clinical detection usually occurs far beyond the neonatal period (8-10).”
From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [8]
The Discussion (page not available) reports a cohort of 34 children with late-diagnosed central congenital hypothyroidism, supporting that clinical diagnosis can be delayed. It does not give their ages at diagnosis or establish that detection usually occurs far beyond the neonatal period. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCongenital central hypothyroidism can be moderate to severe in approximately half of the cases and consequently affect neurodevelopment.
“Congenital CeH can be moderate to severe in approximately half of the cases and consequently affect neurodevelopment [3].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [3]
More than half of patients with central congenital hypothyroidism have moderate to severe hypothyroidism.
“more than half of patients with central CH have moderate to severe hypothyroidism”
From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [8]
Central congenital hypothyroidism is likely to be associated with other pituitary abnormalities.
“Although slightly >50% of neonates with central CH have moderate-to-severe CH, that is, a first diagnostic fT4 concentration of 5–10 pmol/L or lower, and central CH is likely to be associated with other pituitary abnormalities, this diagnosis is often delayed (20,21).”
Slightly more than 50% of neonates with central congenital hypothyroidism have moderate-to-severe congenital hypothyroidism, that is, a first diagnostic free thyroxine concentration of 5-10 pmol/L or lower.
“Although slightly >50% of neonates with central CH have moderate-to-severe CH, that is, a first diagnostic fT4 concentration of 5–10 pmol/L or lower, and central CH is likely to be associated with other pituitary abnormalities, this diagnosis is often delayed (20,21).”
Central CH can be a severe condition (fT4 at diagnosis <5 pmol/L), but most cases can be classified as mild to moderate (fT4 at diagnosis 5-15 pmol/L).
“Central CH can be a severe condition (fT4 at diagnosis <5 pmol/L), but most cases can be classified as mild to moderate (fT4 at diagnosis 5–15 pmol/L) (20,131).”
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References 12 · Cited by 49
- Authors
- Zwaveling-Soonawala, N., van Trotsenburg, A. S. P., & Verkerk, P. H.
- Affiliations
- Netherlands Organisation for Applied Scientific Research (NL)
- ORCID
- Verkerk, Paul H.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-02
- Volume
- 100
- Issue
- 2
- Pages
- E297-E300
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1985051920
- Cited by
- 49
- References
- 12
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 5
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- TNO Repository (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Funders
- European Society of Endocrinology
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- congenital hypothyroidism, central hypothyroidism, disease severity, free thyroxine, newborn screening, children
- MeSH terms
- Child, Preschool, Congenital Hypothyroidism, Female, Humans, Infant, Infant, Newborn, Male, Severity of Illness Index, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine, Neonatal Screening
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