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.
[Show abstract][Hide abstract] ABSTRACT: Purpose of the study is to compare complication rates of bilateral subtotal (BST), near total (NTT) and total thyroidectomy (TT) in a cohort of patients undergoing surgery for benign multinodular goitre (MNG). Seven hundred and fifty patients undergoing surgery for MNG were studied with a median follow-up of 53 months (range 18-102). There was no operative mortality in this group and no patients required urgent re-exploration for haematoma. After BST 14 patients (14/170 - 8.2%) developed transient hypocalcaemia and 4 patients (4/170 - 2.4%) had transient and one permanent (1/170 - 0.6%) recurrent laryngeal nerve (RLN) palsy. In NTT group 39 patients (39/320 - 12.2%) developed transient hypocalcaemia and 2 patients (0.6%) transient voice disturbances. None of the patients in this group experienced permanent complications. However, in TT group 78 patients had (78/260 - 30%) transient hypocalcaemia whereas only one patient (1/260 - 0.4%) suffered permanent hypoparathyroidism and 5 patients (5/260 - 1.9%) had temporary RLN injury but none of them remained permanent. There are only 2 (2/170 - 1.2%) recurrences and those patients are in BST group. All of the patients in BST group required at least 100 microg of thyroxine supplementation following the operation. These results demonstrate low permanent complication rates following thyroid surgery. Although the incidence of transient hypoparathyroidism increases with the extent of the resection, permanent complication rates are similar for all three surgical procedures. Even with short follow-up, there is a risk of recurrence with BST and therefore NTT or TT may be the operation of choice for MNG.
[Show abstract][Hide abstract] ABSTRACT: Pendred syndrome is the most common form of syndromic deafness and characterized by congenital sensorineural hearing loss and goitre. This disorder was mapped to chromosome 7 and the gene causing Pendred syndrome (PDS) was subsequently identified by positional cloning. PDS encodes a putative transmembrane protein designated pendrin. Pendrin is closely related to a family of sulfate transport proteins that includes the rat sulfate-anion transporter (encoded by Sat-1; 29% amino acid sequence identity), the human diastrophic dysplasia sulfate transporter (encoded by DTD; 32%) and the human sulfate transporter 'downregulated in adenoma' (encoded by DRA; 45%). On the basis of this homology and the presence of a slightly modified sulfate-transporter signature sequence comprising its putative second transmembrane domain, pendrin has been proposed to function as a sulfate transporter. We were unable to detect evidence of sulfate transport following the expression of pendrin in Xenopus laevis oocytes by microinjection of PDS cRNA or in Sf9 cells following infection with PDS-recombinant baculovirus. The rates of transport for iodide and chloride were significantly increased following the expression of pendrin in both cell systems. Our results demonstrate that pendrin functions as a transporter of chloride and iodide, but not sulfate, and may provide insight into thyroid physiology and the pathophysiology of Pendred syndrome.
[Show abstract][Hide abstract] 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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