Endocrine Abstracts (2010) 22 P782

Mild hypothyroidism in young patients with congenital heart defects: association with 22q11.2 microdeletion

Passeri Elena1, Frigerio Marcello2, De Filippis Tiziana3, Valaperta Rea2, Costa Elena2, Fugazzola Laura4, Porazzi Patrizia3, Calebiro Davide3, Arcidiacono Carmelo5, Carminati Mario5, Ambrosi Bruno1, Persani Luca3 & Corbetta Sabrina1

1Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy; 2Molecular Biology Laboratory, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy; 3Experimental Endocrine Lab, Department of Medical Sciences, University of Milan, IRCCS Istituto Auxologico Italiano, Cusano Milanino (MI), Italy; 4Endocrine Unit, Department of Medical Sciences, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy; 5Pediatric Cardiosurgery, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy.

Congenital hypothyroidism (CH) is frequently associated with congenital heart defects (CHD). Thyroid defects may have a higher prevalence in children with CHD as embryonic thyroid gland share nuclear transcription factors with heart and great vessels during organogenesis. We investigated thyroid function in 325 children (165 M/160 F, aged 0.2–15.4 years), affected by CHD. Patients with Down syndrome, recent administration of iodinated contrast agents, low T3 syndrome or receiving amiodarone were excluded. Two patients were diagnosed with CH at the neonatal screening. Mild or subclinical hypothyroidism (serum TSH>4.0 μU/ml) was diagnosed in 37 children (11.4%), fully normal at neonatal screening (TSH 5.4±1.5 μU/ml; free T4 1.3±0.2 ng/dl (nv 0.8–1.9)). Increased TSH levels were confirmed six months later. No relationship between hypothyroidism and type of CHD as well as age was detected. TSH levels inversely correlated with free T4 levels (r=−0.115, P=0.044). We investigated the pathogenesis of the mild hypothyroidism. Thyroid autoimmunity with inhomogeneous ecogenicity was present in 3 hypothyroid children (8.1%). Thyroid ultrasound examination was normal in all except one patient with hemiagenesis (2.7%). Patients with CHD and non-autoimmune hypothyroidism (n=36) were screened for genomic variations in candidate genes. NKX2.5 coding sequence was normal in all samples. A qPCR Real-Time analysis detected a 3 Mb microdeletion in 22q11.2 in 3 patients (8.1%). Thus, in the present series mild hypothyroidism affected 50% of the patients with 22q11.2 microdeletion (n=6). Interestingly, one 22q11.2-deleted patient with mild hypothyroidism had a monozygotic twin with TSH 3.44 μU/ml and normal free T4. Mutational screening of the TBX1 gene identified known polymorphisms but did not detect any mutation. In conclusion, a mild hypothyroidism occurs in about 12% of children with CHD and is rarely related to thyroid autoimmunity or dysgenesia. Finally, 22q11.2 deletion is frequently found in CHD patients with nonautoimmune mild hypothyroidism.