A STUDY OF THE MECHANISMS INVOLVED IN THE PRODUCTION OF IODINE-DEFICIENCY GOITER

Abstract

ABSTRACT An extensive study of the temporal sequence of changes in thyroid function after initiation of a low iodine regimen has been made in rats. Variables measured include: thyroid weight, 131I uptake, monoiodotyrosine/diiodotyrosine (MIT/DIT) and triiodothyronine/thyroxine (T3/T4) ratios, iodide clearance, and 127I content. Also measured were protein-bound iodine (PBI), inorganic iodide and thyrotrophin (TSH) levels in the serum. Significant thyroid hypertrophy was produced during the first week and before there was a fall in serum PBI. Temporally related to the appearance of goiter were a rise in 131I uptake, MIT/DIT ratio and iodide clearance and a fall in thyroidal 127I concentration. In contrast, a fall in total thyroidal 127I appeared later and was closely correlated with a decline in serum PBI concentration and a rise in the thyroidal T3/T4 ratio. Manipulations such as hypophysectomy, injections of iodide, thyroxine or TSH, and refeeding a high iodine diet gave results consistent with the view that changes produced by iodine deficiency involve both autonomous and TSH-dependent thyroidal mechanisms. Although elevated serum TSH levels could not be demonstrated until after the first week of the iodine-deficient regimen, the total evidence of these studies permits the conclusion that increased TSH secretion is the most important factor in producing the thyroidal response to iodine deficiency. It is shown that homeostatic mechanisms allow maintenance of a normal level of circulating thyroid hormone in an iodine-deficient state until the body iodine pool becomes too severely depleted to supply adequate iodide substrate to the thyroid. The changes observed closely resemble those found in human iodine-deficient goiters. Although the large goiters produced after several weeks of an iodine-deficient regimen were hyperplastic, they could readily be converted to typical colloid goiters by feeding a high iodine diet for a few days.