Thyroidectomy in a patient with multinodular dyshormonogenetic goitre--a case of Pendred syndrome confirmed by mutations in the PDS/SLC26A4 gene.

Department ofPaediatrics, Second Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Journal of pediatric endocrinology & metabolism: JPEM (Impact Factor: 1). 01/2009; 21(12):1179-84. DOI: 10.1515/JPEM.2008.21.12.1179
Source: PubMed


We report a young woman with genetically confirmed Pendred syndrome and discuss the current therapeutic strategies of dyshormonogenetic goitre. A small diffuse thyroid enlargement developed during infancy and although substitution therapy with L-thyroxine was adequate, it progressed and underwent multinodular transformation. Cervical ultrasound at the age of 22 years demonstrated three solid nodules and fine-needle aspiration biopsy showed a finding typical of follicular adenoma. It is known that dyshormonogenetic goitres have a tendency to grow despite appropriate treatment with L-thyroxine. Management of a patient with Pendred syndrome requires careful follow-up and regular imaging of the thyroid. Although the therapeutic approach to dyshormonogenetic goitres is still controversial, in our patient we chose total thyroidectomy as the most advantageous method to prevent the development of malignancies that may arise more frequently from dyshormonogenetic goitres than from goitres of other aetiologies.

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    ABSTRACT: Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter. The thyroid disease typically develops around puberty and is associated with a mild organification defect, characterized by an inappropriate discharge of iodide upon perchlorate stimulation (a positive perchlorate discharge test). The gene (PDS) mutated in Pendred syndrome is expressed in thyroid and encodes a 780-amino acid protein (pendrin) that has recently been shown to function as an iodide/chloride transporter. We sought to establish the location of pendrin in the thyroid and to examine the regulatory network controlling its synthesis. Using peptide-specific antibodies for immunolocalization studies, pendrin was detected in a limited subset of cells within the thyroid follicles, exclusively at the apical membrane of the follicular epithelium. Interestingly, significantly greater amounts of pendrin were encountered in thyroid tissue from patients with Graves' disease. Using a cultured rat thyroid cell line (FRTL-5), PDS expression was found to be significantly induced by low concentrations of thyroglobulin (TG), but not by TSH, sodium iodide, or insulin. This is different from the established effect of TG, more typically a potent suppressor of thyroid-specific gene expression. Together, these results suggest that pendrin is an apical porter of iodide in the thyroid and that the expression and function of both the apical and basal iodide porters are coordinately regulated by follicular TG.
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