Development of carcinoma of the thyroid in iodine-deficient mice

Abstract

The hypothesis that chronic over-stimulation of the thyroid results in the formation of thyroid neoplasms was tested. After 6 to 12 months of iodine deficiency, 61 of 78 mice demonstrated extreme hypertrophy and hyperplasia of the thyroid. Eleven others had thyroids morphologically consistent with papillary adenocarcinoma. After 18 months of iodine deficiency, necropsy in 8 of 30 mice revealed malignant neoplasms of the thyroid. Initially, iodine deficiency was accompanied by diffuse hypertrophy and hyperplasia of the thyroid, which later became nodular. This progressed to cyst formation, papillary hyperplasia and nodular “solid cell” hyperplasia, sometimes followed by malignant change. These abnormalities appeared to be completely reversed by the addition of potassium iodide to the deficient diet up to 9 months. After 18 months nodular hyperplasia persisted despite treatment with iodine. Iodine deficiency results in decreased synthesis of thyroxin. A deficiency of circulating thyroid hormone causes increased production of TSH by the pituitary, which results in chronic overstimulation of the thyroid gland. Presumably this is the basic mechanism responsible for the development of these abnormalities.