Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (858 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A condition in infancy or early childhood due to an in-utero deficiency of thyroid hormones that can be caused by genetic or environmental factors, such as thyroid dysgenesis or hypothyroidism in infants of mothers treated with thiouracil during pregnancy. Endemic cretinism is the result of iodine deficiency. Clinical symptoms include severe mental retardation, impaired skeletal development, short stature, and myxedema.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Hypothyroidism, Congenital; Cretinism; Myxedema, Congenital; Endemic Cretinism; Cretinism, Endemic; Fetal Iodine Deficiency Disorder.
Where it fits in the MeSH classification
- Broader topics
- Dwarfism; Bone Diseases, Endocrine; Hypothyroidism
- See also
- Myxedema
Related concepts
- Thyroid Hormones
- Hypothyroidism
- Thiouracil
- Mental Retardation
- Myxedema
Research landscape
PubMed indexes 5,145 records tagged with the MeSH heading “Congenital Hypothyroidism” (counts retrieved 2026-10-29). 649 of them (12.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 2,678 records.
Reviews account for 566 records (11.0%) and meta-analyses for 9. Randomized controlled trials number 14 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 2,678 |
| 2000-2009 | 795 |
| 2010-2019 | 1,023 |
| 2020 onward | 649 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 566 | 11.0% |
| Meta-analyses | 9 | 0.2% |
| Randomized controlled trials | 14 | 0.3% |
Method: PubMed query "Congenital Hypothyroidism"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes | 2018 | Research article Design not recorded in structured metadata | 85 | cc by PMID 29650690 · DOI · PMC5958289 |
| Further delineation of Malan syndrome | 2018 | Research article Design not recorded in structured metadata | 64 | cc by PMID 29897170 · DOI · PMC6175110 |
| Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism | 2017 | Research article Design not recorded in structured metadata | 53 | cc by PMID 28633507 · DOI · PMC5587079 |
| Comparison between liquid and tablet formulations in the treatment of congenital hypothyroidism | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42209910 · DOI · PMC13219096 |
The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes [1]
Abstract reading summary — source excerpts
- Opening excerpt
- ObjectiveCongenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment.
- Closing excerpt
- Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (222 words)
ObjectiveCongenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.Design and methodsOne hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.ResultsOur results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.ConclusionsMost cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29650690 · DOI · PMC5958289
Further delineation of Malan syndrome [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Malan syndrome is an overgrowth disorder described in a limited number of individuals.
- Closing excerpt
- Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29897170 · DOI · PMC6175110
Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism [3]
Abstract reading summary — source excerpts
- Opening excerpt
- ContextThe DUOX2 enzyme generates hydrogen peroxide (H2O2), a crucial electron acceptor for the thyroid peroxidase-catalyzed iodination and coupling reactions mediating thyroid hormone biosynthesis.
- Closing excerpt
- Our studies provide evidence for a digenic basis for CH and support the notion that oligogenicity as well as environmental modulators may underlie phenotypic variability in genetically ascertained CH.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (204 words)
ContextThe DUOX2 enzyme generates hydrogen peroxide (H2O2), a crucial electron acceptor for the thyroid peroxidase-catalyzed iodination and coupling reactions mediating thyroid hormone biosynthesis. DUOX2 mutations result in dyshormonogenetic congenital hypothyroidism (CH) that may be phenotypically heterogeneous, leading to the hypothesis that CH severity may be influenced by environmental factors (e.g., dietary iodine) and oligogenic modifiers (e.g., variants in the homologous reduced form of NAD phosphate-oxidase DUOX1). However, loss-of-function mutations in DUOX1 have not hitherto been described, and its role in thyroid biology remains undefined.Case descriptionWe previously described a Proband and her brother (P1, P2) with unusually severe CH associated with a DUOX2 homozygous nonsense mutation (p.R434*); P1, P2: thyrotropin >100 µU/mL [reference range (RR) 0.5 to 6.3]; and P1: free T4 (FT4) C) resulting in aberrant splicing and a protein truncation (p.Val607Aspfs*43), which segregates with CH in this kindred.ConclusionThis is a report of digenic mutations in DUOX1 and DUOX2 in association with CH, and we hypothesize that the inability of DUOX1 to compensate for DUOX2 deficiency in this kindred may underlie the severe CH phenotype. Our studies provide evidence for a digenic basis for CH and support the notion that oligogenicity as well as environmental modulators may underlie phenotypic variability in genetically ascertained CH.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28633507 · DOI · PMC5587079
Comparison between liquid and tablet formulations in the treatment of congenital hypothyroidism [4]
Abstract reading summary — source excerpts
- Opening excerpt
- AimThis study compares the efficacy and safety of three levothyroxine (LT4) formulations in pediatric patients with congenital hypothyroidism (CH).
- Closing excerpt
- However, the clinical relevance of the differences observed at specific time points requires further investigation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (236 words)
AimThis study compares the efficacy and safety of three levothyroxine (LT4) formulations in pediatric patients with congenital hypothyroidism (CH).MethodsThis is a retrospective-prospective observational monocentric study conducted at the Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy. Patients' data were collected from diagnostic confirmation following CH positivity on newborn screening (occurring between January 2019 and April 2024) through age 3 years. According to the LT4 pharmaceutical formulation used in routine clinical practice, patients were assigned to one of three specific groups: T (tablets), D (oral drops), or S (oral solution).Results82 patients were enrolled (group D, N = 30; group S, N = 25; group T, N = 27). At 7-15 days of follow-up, the median TSH concentration was significantly higher in group S compared with group T (p = 0.020). Accordingly, the proportion of patients with serum TSH concentrations above the reference range was significantly higher in group S compared with group T at this time point (p = 0.005). Another difference was observed at 12 months of follow-up, when the proportion of patients with serum fT4 concentrations below the reference range was higher in group D than in groups S and T (p = 0.011). No treatment-related adverse effects were observed with any formulation.ConclusionThe three LT4 formulations were equally effective in normalizing and maintaining serum TSH and fT4 within reference ranges. However, the clinical relevance of the differences observed at specific time points requires further investigation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42209910 · DOI · PMC13219096
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Update of newborn screening and therapy for congenital hypothyroidism [5]
- Research article Congenital hypothyroidism [6]
- Research article Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology [7]
- Research article European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism [8]
- Research article Genetics of congenital hypothyroidism [9]
- Research article Screening for congenital hypothyroidism: a worldwide view of strategies [10]
References
- Sun F, Zhang JX, Yang CY, Gao GQ, Zhu WB, Han B, et al.. The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes. . 2018. PMID 29650690 · DOI · PMC5958289
- Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, et al.. Further delineation of Malan syndrome. . 2018. PMID 29897170 · DOI · PMC6175110
- Aycan Z, Cangul H, Muzza M, Bas VN, Fugazzola L, Chatterjee VK, et al.. Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism. . 2017. PMID 28633507 · DOI · PMC5587079
- Parzianello A, Cantarelli E, Bortolamedi E, Candela E, Cassio A, Baronio F, et al.. Comparison between liquid and tablet formulations in the treatment of congenital hypothyroidism. . 2026. PMID 42209910 · DOI · PMC13219096
- American Academy of Pediatrics, Rose SR, Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS, Public Health Committee, et al.. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006. PMID 16740880 · DOI
- Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010. PMID 20537182 · DOI · PMC2903524
- van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, et al.. Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021. PMID 33272083 · DOI · PMC8001676
- Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, et al.. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014. PMID 24446653 · DOI · PMC4207909
- Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005. PMID 15863666 · DOI · PMC1736062
- Ford G, LaFranchi SH. Screening for congenital hypothyroidism: a worldwide view of strategies. Best Pract Res Clin Endocrinol Metab. 2014. PMID 24629860 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.