CONTEXT: Pendred syndrome is caused by mutations in the gene coding for pendrin, 
an apical Cl-/I- exchanger.
OBJECTIVE: To analyze intrathyroidal compensatory mechanisms when pendrin is 
lacking, we investigated the thyroid of a patient with Pendred syndrome. The 
expression of proteins involved in thyroid hormone synthesis, markers of 
oxidative stress (OS), cell proliferation, apoptosis, and antioxidant enzymes 
were analyzed.
RESULTS: Three morphological zones were identified: nearly normal follicles with 
iodine-rich thyroglobulin in the colloid (zone 1.a), small follicles without 
iodine-rich thyroglobulin in lumina (zone 1.b), and destroyed follicles (zone 
2). In zones 1.a, dual oxidase (Duox) and thyroid peroxidase (TPO) were 
localized at the apical pole, OS and cell apoptosis were absent, but ClC-5 
expression was strongly increased. In zones 1.b, Duox and TPO were aberrantly 
present and increased in the cytosol and associated with high OS, apoptosis, 
cell proliferation, and increased expression of peroxiredoxin-5, catalase, and 
dehalogenase-1 but moderate ClC-5 expression.
CONCLUSION: In conclusion, the absence of pendrin is accompanied by increased 
ClC-5 expression that may transiently compensate for apical iodide efflux. In 
more affected follicles, Duox and TPO are relocated in the cytosol, leading to 
abnormal intracellular thyroid hormone synthesis, which results in cell 
destruction presumably because intracellular OS cannot be buffered by 
antioxidant defenses.