Congenital goiter and the development of metastatic follicular carcinoma with evidence for a leak of nonhormonal iodide: clinical, pathological, kinetic, and biochemical studies and a review of the literature.

We report a large kindred of patients with congenital goiter, followed for 15 yr, in which two siblings (one male and one female) developed metastatic follicular thyroid carcinoma. These two patients were evaluated by iodine kinetic analysis. None of the classical defects of T4 biosynthesis was present in either patient. Rather, both patients had extremely rapid rates of iodine turnover, with elevated 131I uptake and excessive spillage of iodide in the urine. Serum iodoalbumin was present, probably as a nonspecific result of glandular hyperplasia. Iodine kinetic analysis after the ingestion of potassium perchlorate and methimazole was compatible with a leak of nonhormonal iodide from the thyroid. It is not possible to determine whether this iodide leak is the primary pathogenetic defect or is secondary to another unidentified abnormality. The unprecedented development of metastatic thyroid cancer in patients with congenital goiter occurred, in both instances years after subtotal thyroidectomy without thyroid hormone replacement therapy, suggesting a role for TSH in the genesis of human thyroid cancer. On the basis of our study of these patients and a review of the literature, we conclude that TSH is likely to be a factor in the induction of human follicular thyroid carcinoma.