Goitrogens and thyroid follicular cell neoplasia: evidence for a threshold process

Thyroid neoplasia can result from many different causes. These include low iodine diets, subtotal thyroidectomy, radioactive iodine, natural goitrogens such as rape seed and cabbage, chemotherapeutic agents such as sulfathiazole, and pesticides such as amitrole. All of these appear to act through either direct or indirect interference with thyroid hormone synthesis. Decreased circulating levels of thyroid hormones in the blood result in increased release of thyroid-stimulating hormone by the anterior pituitary gland. This, in turn, results in hypertrophy and hyperplasia of the thyroid without a corresponding increase in blood thyroid hormone levels. Hyperplasia of the pituitary is also observed due to increased functional demand for continued production of thyroid-stimulating hormone. After prolonged stimulation of the pituitary/thyroid axis, hyperplasia may progress to neoplasia. Cessation of exposure prior to the induction of neoplasia results in a return to the normal state. It is clear that some degree of thyroid inhibition can be accommodated within the bounds of the normal feedback mechanism without the induction of either hyperplasia or neoplasia. A threshold for thyroid follicular neoplasia is therefore indicated.