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Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects
E Passeri1, M Frigerio, T De Filippis
1Endocrinology and Diabetology Unit, Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Italy. luca.persani@unimi.it
Insights
Children with congenital heart defects (CHD) have a significantly higher risk of developing congenital hypothyroidism (CH) and mild acquired hypothyroidism. Early detection and regular monitoring of thyroid function are crucial for managing these patients.
Area of Science:
- Pediatric Endocrinology
- Cardiology
- Genetics
Background:
- Newborns with congenital hypothyroidism (CH) face an elevated risk of congenital heart defects (CHD) due to shared embryonic developmental pathways.
- The study explores the connection between thyroid disorders and CHD in pediatric patients.
Purpose of the Study:
- To determine the prevalence and underlying causes of thyroid disorders in young patients diagnosed with CHD.
- To investigate the relationship between thyroid dysfunction and the characteristics of congenital heart disease.
Main Methods:
- A prospective observational study was conducted from January 2007 to January 2009.
- 324 children (aged 0.2-15.4 years) with CHD underwent hormonal and genetic screening, including assessment of serum TSH and thyroid hormone levels.
- Genetic analysis focused on candidate genes and microdeletions, including 22q11.2.
Main Results:
- The prevalence of CH was 1:162 among CHD patients. Mild hypothyroidism was identified in 11.5% of children negative for CH at neonatal screening.
- Hypothyroidism was not associated with specific CHD types, but TSH levels correlated with N-terminal pro-type B natriuretic peptide.
- Thyroid autoimmunity was found in 8.1% of hypothyroid children, and 22q11.2 microdeletions were detected in 8.3% of CHD patients.
Conclusions:
- Patients with CHD exhibit a 10-fold higher risk of CH and a 3-fold higher risk of acquired mild hypothyroidism.
- Undiagnosed mild hypothyroidism can adversely impact CHD outcomes, necessitating regular thyroid function monitoring.
- While thyroid autoimmunity and 22q11.2 microdeletions contribute to a small fraction of cases, the strong association between CHD and thyroid disorders suggests unknown underlying mechanisms.
Context:
Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels.
Objective:
Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD.
Design And Setting:
We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology.
Patients:
Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD.
Intervention:
Subjects underwent hormonal and genetic screening.
Main Outcome Measures:
Serum TSH and thyroid hormone levels were assessed.
Results:
Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 μU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 μU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence.
Conclusions:
CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.
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