Biallelic mutations of SLC26A4 (encoding pendrin) cause Pendred syndrome (PS), 
an autosomal recessive genetic disorder with deafness and goiter. The mechanism 
underlying the development of the goiter is unknown. Here, we report clinical 
and molecular findings of a patient with PS. This 27-year-old woman was born to 
nonconsanguineous healthy parents. She was seen at our hospital due to hearing 
loss at age 3 years, and subsequently developed goiter at age 10 years. From age 
15 years, her thyroid gland showed progressive enlargement accompanied by 
elevation of serum thyroglobulin reaching 10-fold the normal amount. Thyroidal 
iodine uptake was also increased during goiter progression ((123)I uptake at 24 
hr: 20.2% at age 17 years; 69.4% at age 24 years; reference, 8-40), while serum 
thyrotropin (TSH) levels and iodine organification (examined by the perchrolate 
or thiocyanate discharge test) remained normal. We sequenced SLC26A4 using 
standard PCR-based technique, and found one novel (p.T537P) and one recurrent 
(p.H723R) mutations in a compound heterozygous state. Expression experiments 
using COS-7 cells showed that the two mutants were entrapped in the endoplasmic 
reticulum and were poorly localized at the plasma membrane. In summary, a 
molecularly confirmed PS patient showed goiter progression accompanied by 
elevated serum thyroglobulin and increased thyroidal iodine uptake, but normal 
serum TSH levels and normal iodine organification. This implies that some 
pendrin mutations may involve direct stimulation of thyroid cell proliferation 
with no TSH hyperstimulation and no iodine organification defect.