In this article we describe detailed pathological and molecular genetics studies 
in a consanguineous kindred with Pendred's syndrome. The index patient was a 
53-year-old female patient with congenital deafness and goiter. Her parents were 
first-degree cousins. She had a large goiter (150 g) that had been present since 
childhood. One of her sisters and a niece are also deaf and have goiter as well. 
The presence of Pendred's syndrome was confirmed by a positive perchlorate test 
and the demonstration of a Mondini malformation. Thyroid function tests (under 
levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin 
[TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 
nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L 
(0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was 
found to have invaded adjacent tissues. The histopathological findings were 
consistent with a follicular carcinoma with areas of anaplastic transformation 
and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 
MBq) and received suppressive doses of LT4. Postoperatively, the serum 
thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). 
The patient died of a sudden severe episode of hemoptysis. Sequence analysis of 
the PDS gene performed with DNA from the two relatives with Pendred's syndrome 
revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation 
that results in a frameshift and a premature stop codon at codon 96 in the 
pendrin molecule. We concluded that prolonged TSH stimulation because of iodine 
deficiency or dyshormonogenesis in combination with mutations of oncogenes 
and/or tumor suppressor genes, may result in the development of follicular 
thyroid carcinomas that undergo transformation into anaplastic cancers. It is 
likely that these pathogenetic mechanisms have been involved in the development 
of aggressive metastatic thyroid cancer in this unusual patient with Pendred's 
syndrome.