Endocrine Abstracts

Pendred syndrome (PS) is an autosomal, recessive disorder characterized by sensorineural deafness, goiter, and a positive perchlorate test. PS, one of the most common forms of syndromic deafness, is caused by biallelic mutations in the SLC26A4 gene, which encodes the anion transporter pendrin. Functionally, pendrin can serve as an exchanger of several anions including chloride, bicarbonate and iodide. Pendrin is expressed in the inner ear, the thyroid and the kidney.

The phenotypic expression of goiter and deafness is variable. Some individuals develop very large goiters, others present with no thyroid enlargement. This variability is probably influenced by the nutritional iodide intake. Under conditions of normal iodide intake, patients with PS are usually euthyroid, but if the iodide supply is scarce, overt hypothyroidism may develop. Sensorineural hearing loss, usually profound prelingual deafness, is the hallmark of PS. High-resolution imaging of the inner ear reveals malformations of the vestibular aqueduct, and the endolymphatic duct and sac in nearly 100% of individuals with PS. In the absence of a goiter, the (familial) finding of an enlarged vestibular aqueduct (EVA) may point to the non-syndromic form of deafness caused by biallelic SLC26A4 gene mutations.

In the inner ear, pendrin is involved in chloride/bicarbonate exchange and the maintenance of the endocochlear potential. In thyroid follicular cells, pendrin is inserted into the apical membrane. Functional studies suggest that pendrin may be involved in the efflux of iodide into the follicular lumen. Inactivating mutations of pendrin impair the efflux of iodide, which may explain the partial organification defect. Alternatively, pendrin could be of importance in maintaining an optimal follicular pH necessary for the organification of iodide. In the kidney pendrin acts as a chloride-bicarbonate exchanger in beta-intercalated cells of the cortical collecting duct, a subpopulation of cells that mediate bicarbonate secretion.