title: Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology.
  
  
  METHODS
  Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD.
  
  
  METHODS
  Subjects underwent hormonal and genetic screening.
  
  
  METHODS
  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.
authors.affiliation: Endocrinology 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
authors.forename: E
authors.initials: E
authors.lastname: Passeri
authors.forename: M
authors.initials: M
authors.lastname: Frigerio
authors.forename: T
authors.initials: T
authors.lastname: De Filippis
authors.forename: R
authors.initials: R
authors.lastname: Valaperta
authors.forename: P
authors.initials: P
authors.lastname: Capelli
authors.forename: E
authors.initials: E
authors.lastname: Costa
authors.forename: L
authors.initials: L
authors.lastname: Fugazzola
authors.forename: F
authors.initials: F
authors.lastname: Marelli
authors.forename: P
authors.initials: P
authors.lastname: Porazzi
authors.forename: C
authors.initials: C
authors.lastname: Arcidiacono
authors.forename: M
authors.initials: M
authors.lastname: Carminati
authors.forename: B
authors.initials: B
authors.lastname: Ambrosi
authors.forename: L
authors.initials: L
authors.lastname: Persani
authors.forename: S
authors.initials: S
authors.lastname: Corbetta
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000150:complications*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D011446:Prospective Studies; D012306:Risk; D012720:Severity of Illness Index; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D013963:Thyroid Hormones