Acid protease activity in thyroid gland from patients with Graves' disease

Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T 3 T 4 ratio Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic. This suggests that one of the mechanism involved in the suppressive effect of excess iodide on the secretory process of the Graves' thyroid may be the inhibition of lysosomal protease.