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Male Fischer rats were fed a low-iodine diet containing thiouracil for 21 days to produce hyperplastic thyroid glands, and then fed a high-iodine diet for various time intervals, from 5 hr to 180 days, in order to study the morphological changes that occur during involution. Thyroids were fixed by perfusion fixation and embedded in Epon. Sections were examined by light microscopy. Initially at 0 days of involution (at the time of the change to the high-iodine diet), follicular lumens were very narrow and capillary lumens were very wide. The capsule was thick and infiltrated with mononuclear leukocytes. No obvious changes occurred for 1 day after the change in diet, but shortly thereafter capillary lumens began to narrow. By 4 days, most capillary lumens were close to normal size; capillaries formed a more or less normal bed except that many were embedded in a relatively thick or wide interfollicular matrix. This matrix was largely gone by 21 days. Between 1 and 21 days, follicular lumens dilated progressively as colloid accumulated. The density of staining of the accumulated colloid varied from follicle to follicle, and this variation was also observed in older controls. Inflammatory cells gradually disappeared from the capsule and most were gone by 15 days. Starting at approximately 15 days and continuing to 180 days, one or more disintegrating cells were found in some lumen profiles. Colloid goiters were not observed in these rats even after several months of involution. Some lumens were rather large, however, and small fractions of the follicles, both small and large, were bounded by flat cells and resembled "cold" follicles morphologically.

Young adult male Fischer rats were fed 0.25% thouracil in a low-iodine diet to produce hyperplasia of the thyroid gland. The capsule of the thyroid gland increased in thickness from approximately one cell in controls to a substantial multilayered structure. Increase in capsule thickness was noted by 3 days. The cell population of the capsule was largely fibroblasts, but during a period within the interval from 14 to 28 days, the capsule tended to be exceptionally thick and contained many mononuclear leukocytes. At later times the capsule was not quite as thick and the leukocytes largely disapproved. Capillaries developed in the capsule probably by sprouting. The capsule growth was so extensive that certain neighboring tissues were often incorporated into the capsule, including arteries, veins, nerves, striated muscle, and lymph nodes. There was some regional specificity in the development of capsular hyperplasia. Connective tissue increased around the thyroid and parathyroid glands but not between them. Connective tissue in partitions with the thyroid gland also increased in thickness, although the extent of accumulation of cells and intercellular matrix was much less than in the capsule.

To study blood capillary growth in the hyperplastic thyroid gland, rats were fed 0.25% thiouracil in a low iodine diet for time intervals up to 100 days. Thyroids were fixed by vascular perfusion and embeded in Epon. Whole lobes were sectioned from pole to pole and slides were prepared of sections every 0.3 mm. Capillaries were clearly enlarged by 3 days and they enlarged progressively thereafter. By 3 days, the cells of many neighboring capillaries came into close apposition and from this time on, there was evidence of fusion of capillary walls in the form of partial septa in the capillary lumens. Fusion continued until 20 days, when follicles were almost completely surrounded by a continuous endothelial sheet and unfused capillary walls were separated by connective tissue. The vascular pattern around peripheral follicles changed in a way similar to interior follicles, except that in places, capillaries were gradually excluded from the space between epithelium and thyroid capsule. Vascular enlargement was restricted to the thyroid blood vessels. There was no obvious enlargement of the blood capillaries of the parathyroid despite its close proximity to the thyroid.