Demonstration of iodide transport defect but normal iodide organification in nonfunctioning nodules of human thyroid glands

Benign and malignant nodules in human thyroid glands, which did not concentrate iodide in vivo, were also unable to accumulate iodide in vitro. The mean thyroid-to-medium ratio (T/M) in seven benign nodules was 0.8+/-0.2 compared with 7+/-2 in adjacent normal thyroid tissue. In four malignant thyroid nodules, the mean T/M was 0.5+/-0.1 compared with 11+/-4 in adjacent normal thyroid. Despite the inability of such nodules to concentrate iodide, iodide organification was present but was only one-half to one-third as active as in surrounding normal thyroid. Thyroid-stimulating hormone (TSH) increased iodide organification equally in both benign nodules and normal thyroid although it had no effect in three of the four malignant lesions. The reduction in organification is probably related to the absence of iodide transport, since incubation of normal thyroid slices with perchlorate caused similar diminution in iodide incorporation but no change in the response to TSH. Monoiodotyrosine (MIT) and di-iodotyrosine (DIT) accounted for most of the organic iodide in both the nodules and normal tissue. The MIT/DIT ratio was similar in normal and nodule tissue. The normal tissue contained much more inorganic iodide than the nodules, consistent with the absence of the iodide trap in the latter tissue. The thyroxine content of normal thyroid was 149+/-17 mug/g wet wt and 18+/-4 mug/g wet wt in the nodules. The transport defect in the nodules was not associated with any reduction in total, Na(+)-K(+)- or Mg(++)-activated ATPase activities or the concentration of ATP. Basal adenylate cyclase was higher in nodules than normal tissue. Although there was no difference between benign and malignant nodules, the response of adenylate cyclase to TSH was greater in the benign lesions. These studies demonstrate that nonfunctioning thyroid nodules, both benign and malignant, have a specific defect in iodide transport that accounts for their failure to accumulate radioactive iodide in vivo. In benign nodules, iodide organification was increased by TSH while no such effect was found in three of four malignant lesions, suggesting additional biochemical defects in thyroid carcinomas.