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*

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Abstract
Patients with congenital goiter followed for 15 yr, are reported in which 2 siblings (1 male and 1 female) developed metastatic follicular thyroid carcinoma. These 2 patients were evaluated by I kinetic analysis. None of the classical defects of thyroxine biosynthesis was present in either patient. Both patients had extremely rapid rats of I turnover, with elevated 131I uptake and excessive spillage of I- in the urine. Serum iodoalbumin was present, probably as a nonspecific result of glandular hyperplasia. I kinetic analysis after the ingestion of potassium perchlorate and methimazole was compatible with a leak of nonhormonal I- from the thyroid. It is not possible to determine whether this I- 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 [thyrotropin] in the genesis of human thyroid cancer. On the basis of this study and a review of the literature, it was concluded that TSH is likely to be a factor in the induction of human follicular thyroid carcinoma.