A patient with Pendred syndrome whose goiter progressed with normal serum thyrotropin and iodine organification.

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.