Severe Permanent Congenital Hypothyroidism (CH) with Apparent Athyreosis: Absence of TSH Receptor (TSHR) Gene Mutations

P. SCAGLIA; L. GRUÑEIRO-PAPENDIECK; P. PAPENDIECK; L. PRIETO; H.M. DOMENÉ; A. CHIESA

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Severe Permanent Congenital Hypothyroidism (CH) with Apparent Athyreosis: Absence of TSH Receptor (TSHR) Gene Mutations P. Scaglia, L. Gruñeiro-Papendieck, P. Papendieck,L. Prieto, H.M. Domene, A. Chiesa Division de Endocrinologia Hospital de Niños Gutierrez, Buenos Aires, Argentina Introduction and Objectives: Apparent athyreosis (AA) (negative 99Tc thyroid scan uptake with hypoplastic thyroid on ultrasound or detectable TG levels) represents 7% of permanent CH detected in our neonatal screening program and 30% of athyreotics. Material and methods: To search for mutations in TSHR gene, we selected 21 CH with AA detected by neonatal screening. 14/21 CH had negative thyroid scan, positive US and median TG 27 ng/ml (1.8?65). The remaining 7 had negative scan and US and TG levels of 49 ng/ml (6.8?81). All have negative anthythyroperoxidase and anti-thyroglobulin antibodies. The whole coding sequence of TSHR gene (exons 1?10) and intronic flanking regions were amplified by PCR from genomic DNA and automatically sequenced. Results: Sequenciation of TSHR gene revealed 4 different SNPs in heterozygous state in 9 patients: 1 P52T (rs2234919), 4 N187N (rs2075179), 2 D727E (rs1991517), 1 D727E/ N187N and 1 D727E/A459A (rs 113951800). No novel or previously described mutations associated with CH were found. Conclusion: TSHR gene mutations appear to be uncommon in AA in our population. Although a functional effect of TSHR polymorphisms could not be ruled out, previous studies of SNPs does not support this hypothesis