Pathological findings in dyshormonogenetic goiter with defective iodide transport

An adult male patient (38 yr old) with a large congenital goiter with hypothyroidism was suspected of having a defective iodide (I-) transport mechanism based on low thyroid uptake and a very low salivary/plasma ratio. Moreover the high serum levels of TSH (104 mu U/mL) declined to 7.2 mu U/mL with a corresponding normalization of serum total T4 concentration, after 40 d of treatment with Lugol's solution (6 mg I/d). Thyroid surgery was performed because a fine-needle aspiration biopsy of a nodule revealed atypical cells associated with the presence of a large compressive goiter (150 g). Pathologic examination indicated histological findings compatible with the hyperplastic pattern with predominant microfollicular aspect. Immunostaining for other specific thyroid proteins, thyroid peroxidase (TPO) and Tg, indicated normal expression of both transcripts. Electron microscopy (x13,000) showed the ultrastructural aspects of a hyperactive follicular cell with folding of the basal membrane. Sequencing of the entire sodium/iodide (Na/I) symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide 1163 with an adenine, resulting in a stop signal at codon 272. This nonsense mutation produces a truncated NIS symporter protein without iodide transport activity. Although the propositus is homozygotic for the NIS-272X expression of one normal allele in the heterozygotic son, mother, and paternal aunt is sufficient to maintain normal thyroid function.