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Clinical, biochemical, and molecular findings in Argentinean patients with goitrous congenital hypothyroidism

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Abstract

We describe the clinical, biochemical, and molecular findings of a cohort of Argentinean patients with congenital hypothyroidism (CH) and goiter studied to characterize iodide organification and thyroglobulin (TG) defects. 20 CH patients (16 unrelated) were grouped according to serum TG levels and a perchlorate discharge test (PDT) in: group 1 (G1): nine patients with high TG and PDT > 10% who were studied for tiroperoxidase (TPO), dual oxidase 2 (DUOX2), and dual oxidase A2 (DUOXA2) defects and group 2 (G2): 11 patients with low TG and PDT < 10% studied for TG defects. Goiter characteristics, outcome, and TT4 and TT3 levels without treatment were compared between groups. 6/9 G1 patients harbored mutations in TPO gene and 3/9 in DUOX2 gene. In G2, mutations of TG gene were found in 3/11 homozygous, 5/11 compound heterozygous, and 3/11 heterozygous patients. Goiter was only evidenced by thyroid scan in the neonatal period in both groups; was moderately enlarged in patients diagnosed during infancy. In the late detected patients, goiter was big and nodular in G1 while diffuse and moderate in G2. Early detected patients grew and developed normally while those diagnosed late were severely mentally retarded in G1 and only mildly retarded in G2. Thyroid hormone levels of G1 were significantly lower than those of G2 P < 0.01. Molecular approach to characterize defects in organification and TG defects was optimized by TG measurements and PDT. Clinical and biochemical differences based on molecular findings will allow further investigations on genotype–phenotype relationships.

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Abbreviations

CH:

Congenital hypothyroidism

TG:

Thyroglobulin

TPO:

Thyroid peroxidase

DUOX2:

Dual oxidase 2

DUOXA2:

Dual oxidase A2

(DEHAL1):

Iodotyrosine dehalogenase 1

PDT:

Perchlorate discharge test

TSH:

Thyrotropin

TT4 :

Total thyroxin

TT3 :

Total triiodotironine

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Acknowledgments

Ana Chiesa is a research associate member of the Gobierno de la Ciudad de Buenos Aires. C. M. Rivolta and H. M. Targovnik are established investigators of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). This work was supported by grants from Universidad de Buenos Aires (B 078/2008 to HMT), CONICET (PIP 5360/2005 and PIP 112-2000801-0054 to CMR and HMT) and ANPCyT-FONCyT (05-21081/PICT 2004 to HMT). We thank Dr. Saul Malozowski for the critical reading of the manuscript.

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  1. División Endocrinología, Hospital de Niños “Ricardo Gutiérrez”, Centro de Investigaciones Endocrinológicas, CEDIE-CONICET, Gallo 1330, 1425, Buenos Aires, Argentina

    Ana Chiesa & Laura Gruñeiro-Papendieck

  2. Laboratorio de Biología Molecular, Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113, Buenos Aires, Argentina

    Carina M. Rivolta & Héctor M. Targovnik

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  1. Ana Chiesa
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  2. Carina M. Rivolta
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  3. Héctor M. Targovnik
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  4. Laura Gruñeiro-Papendieck
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Correspondence to Ana Chiesa.

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Chiesa, A., Rivolta, C.M., Targovnik, H.M. et al. Clinical, biochemical, and molecular findings in Argentinean patients with goitrous congenital hypothyroidism. Endocr 38, 377–385 (2010). https://doi.org/10.1007/s12020-010-9391-8

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