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In vitro lysosomal acid protease activity was studied in human papillary thyroid carcinoma (n = 13). As a control, morphologically normal thyroid tissue from the same patient was used in each individual case of carcinoma. Although a marked variation may be observed between individual cases, each examined papillary thyroid carcinoma showed significantly greater activity of acid proteases, both per unit weight of wet thyroid tissue and per unit of lysosomal proteins, in comparison to the corresponding control (range, 24%-248%). In conclusion, it is suggested that enhanced proteolytic activity of lysosomal acid proteases in papillary carcinoma is probably a result of disturbance in catabolic degradation of the thyroglobulin molecule in malignantly transformed thyroid tissue.

Thyroid auto-proteolytic activity in rats increased significantly only after several weeks of treatment with 1 mg iodide per day. Iodide added in vitro did not activate thyroid auto-proteolysis, nor was inhibition observed. Thyroid proteolytic activity was also tested using 131I-labelled heat-inactivated thyroid homogenate from control rats as substrate. Significantly increased proteolytic activity was again demonstrated in thyroid glands from rats on excess iodide for several weeks. The increased proteolytic activity is therefore probably not due to a decreased proteolytic resistance of thyroglobulin in the iodide-treated rats. Increased synthesis or decreased degradation of thyroid proteolytic enzymes is a more likely explanation for this phenomenon. These findings are at variance with those of some previous studies showing decreased proteolytic activity in thyroid glands from rats administered excess iodide. Since the rats remained euthyroid the increased auto-proteolysis, which occurred quite late, was considered an unexpected finding and it is at present not certain whether this is related to the successful adaptation. Treatment with iodide did not alter the thyroid and hypophyseal weight or histology. Serum free thyroxine level and thyrotrophin concentration were also unaffected by excess iodide. The adaptation of the intact rat thyroid to prolonged and excess iodide intake seems to occur without the assistance of an altered thyrotrophin secretion.

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The significance of stable iodine in the formation of thyroglobulin (TG) with particular reference to the aggregation of subunits into TG and the formation of 27S iodoprotein has been investigated in guinea-pigs and rabbits. An increase in the content of iodine in the diet or its parenteral application to normally fed animals results in considerable quantitative and qualitative changes in the soluble thyroid proteins as revealed by analytical ultra-centrifugation and sucrose density gradient centrifugation. Although some differences in the protein patterns between guinea-pigs and rabbits normally exist, the changes induced by single and repeated doses of stable iodine (5–100 μg/day) were characterized by: (a) decrease of light proteins, particularly the 12S protein fraction in the guinea-pig; (b) a marked increase of TG and (c) the appearance of a quantity of 27S iodoprotein. These changes in composition of the thyroid soluble proteins are accompanied by changes in the radioiodine distribution among the protein fractions. The results obtained suggest that the process of thyroid protein polymerization and the process of their iodination are not independent of each other. The level of the supply of the thyroid gland with iodine under normal iodine metabolic conditions considerably influences both the aggregation of subunits into TG and the formation of 27S iodoprotein. It is likely that 27S iodoprotein is formed when larger quantities of normally iodinated TG are synthesized and stored in the gland.

Oestratetraenol is an artifact arising from oestradiol-17α during acid hydrolysis of bovine urine. This finding led us to investigate the influence of acid concentration and time of heating on the yield of these two substances as compared with enzyme hydrolysis. For oestradiol-17α enzyme hydrolysis resulted in a 5 to 6 times higher yield than acid hydrolysis (6 vol.% HCl. 1 hour at 100° C). The results being the same whether the starting material was natural urine or previously extracted conjugates. When acid hydrolysis was used as mentioned above, the conversion of pure oestradiol-17α to oestratetraenol was of the order of 10 to 15%. In view of the extreme lability of oestradiol-17α to acid hydrolysis and its partial transformation to oestratetraenol, the problems of acid hydrolysis of bovine urinary oestrogen conjugates are discussed.

Increased thyroglobulin (Tg) serum level in females (n = 49) suffering from scintigraphically "cold" thyroid nodule (395 +/- 168, micrograms/l, mean +/- SD) is significantly higher (p less than 0.001) in comparison with the data obtained from euthyroid healthy persons (28 +/- 10, n = 15) or those diagnosed with scintigraphically functional thyroid nodule (72 +/- 14, n = 15). No correlation between Tg and TSH serum levels has been seen before surgical removal of "cold" nodule (rxy = +0.34). In 49 out of 75 cases (65.3%) struma colloids were confirmed pathohistologically. After surgery, "cold" thyroid nodule was removed, serum Tg level decreased progressively within several days and three months afterwards, Tg level in most patients was mainly within the normal range for a healthy subject. The positive correlation between Tg and TSH was established three months after surgical removal of the nodule (rxy = +0.90). An elevation of serum Tg level was found in 16 out of the 49 patients during different postoperative periods (from 2 to 9 years). Under thyroxine treatment, in most of these patients a significant decrease of serum Tg level was observed. However, in a few treated patients, no change in Tg level was seen. Further clinical control in thyroxine-nonsuppressive patients discovered a compensatory hypertrophy of thyroid tissue and the appearance of a new thyroid nodule later. Present data and clinical experience suggest that long-term follow-up of serum Tg level in patients after surgical removal of "cold" thyroid nodule, brings about to early diagnosis of thyroid tissue postoperative hypertrophy before the appearance of thyroid gland nodule relapse.

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