TRANSFORMATION OF NORMAL THYROIDS INTO COLLOID GOITERS IN RATS AND MICE BY DIPHENYLTHIOHYDANTOIN

Some years ago, we reported that colloid goiters could be produced exp erimentally in mice and rats by injection of TSH over a few days in th e presence of ample iodine supply. This clearly showed that colloid ac cumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological a nd biochemical characteristics with human colloid goiters, were induce d in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPT H). This drug increases fecal loss of thyroid hormone and inhibits con version of T-4 to T-3. Thus, DPTH raises TSH and induces macrofollicul ar colloid-rich goiters. In contrast to this, goiters induced by combi ned treatment with methimazole (MMI) or sodium perchlorate and DPTH ar e microfollicular, although serum TSH is increased to the same level a s in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter fo llicles or if it will expand its hull. Thyroglobulin content of DPTH g oiters is lower than that of normal glands but considerably higher tha n after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inh ibition of iodine organification and hormone synthesis by DPTH, but mu ch less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the collo id by macrophages and granulation tissue. Therefore, DPTH goiters migh t well be a useful model. not only for colloid goiter formation but al so for inflammatory processes in the thyroid gland.