Kinetics of the iodide trapping mechanism in thyroid slices was studied in human and animal tissues. Slices were incubated with several medium iodide concentrations, ranging from 5 \m=x\10\m=-\6 m to 2 \m=x\10\m=-\4 m, in order to calculate in the steady state the following kinetic parameters of the iodide transport: Km, maximal capacity (C) and diffusion factor (D).Results indicated that the Km was similar in magnitude (10\m=-\5 m) in all cases where trapping activity was present, while maximal capacity (C) values showed significant differences between those pathologies in which trapping activity was hyperstimulated (dishormonogenetic goitre, Graves' disease, toxic adenoma) and those where thyroid tissues presented focal or total alterations on its structure (non-toxic nodular goitre, Hashimoto's thyroiditis, thyroid cancer) or where thyroid tissues were not sufficiently stimulated by TSH (extranodular tissue of toxic adenoma). 'Warm' nodules were not significantly different from normal human thyroid. These results suggest that the scattered trapping values observed in the different thyroid pathologies correspond to quantitative differences between them rather than to qualitative alterations in the thyroid iodide pump.

A 71-yr-old man, clinically euthyroid, with a 570-g goiter causing severe mechanical neck compression underwent thyroidectomy. His total serum T4 level was 1.8 micrograms/dL, T3 was 200 ng/dL, and TSH was 35 microU/mL, and a perchlorate test was markedly abnormal. The excised thyroid tissue had normal peroxidase activity in the tyrosine iodinase and guaiacol assays. [131I]Iodide, given 24 h before surgery, was distributed in thyroglobulin isolated in vitro as follows: monoiodotyrosine, 71.6%; diiodotyrosine, 26.7%; T3, 1.05%; and T4, 0.65%. The [131I]iodide content of the whole thyroid homogenate was 59%. The goiter content of thyroglobulin was 94.7 mg/g tissue. The thyroglobulin reacted normally with antihuman thyroglobulin antiserum. Fresh goiter slices and slices from five normal human thyroid specimens were incubated with 10(-6) M KI and [131I]iodide (tracer) containing medium alone (basal), medium plus 1 mg/mL glucose oxidase (GO), and medium plus 10(-4) M NADPH and 10(-5) M vitamin K3 (NA-K3). The percentages of organic iodine in the slices, measured as protein-bound 131I, were: basal: goiter, 0.8%; normal, 6.9 +/- 1.8% (+/- SE); GO: goiter, 15.1%; normal, 17.4 +/- 3.1%; and NA-K3: goiter, 16.7%; normal, 4.6 +/- 1.14%. We conclude that an abnormal H2O2 supply may be the cause of the iodine organification defect in this goiter.

Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,5-diiodo, benzoyl) benzofuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10\m=-\4m and 10\m=-\5 M, showing a decrease of T/M (tissue/medium) ratios of 20 % and 23 %, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10\m=-\4 m and 10\m=-\5 m amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20 % decrease at 10\m=-\3 m amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7 % at a concentration of 10\m=-\4 m. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10\m=-\3 m and 10\m=-\4 m. The inhibitions were of 22.5 % and 16.8 %, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.

Several alterations of thyroid function parameters have been reported in patients treated with phenylbutazone and we have studied the effect of this drug on the intrathyroidal iodine metabolism. An inhibition of the iodide transport expressed in terms of T/M ratios was observed in bovine thyroid slices incubated with high phenylbutazone concentrations. 10\m=-\3m produced 72% inhibition whereas lower concentrations showed no significant difference as compared with controls. Iodotyrosine synthesis was affected by 10\m=-\4m and 10\m=-\5m phenylbutazone. Formation of iodothyronine synthesis was markedly affected between 10\m=-\4m and 10\m=-\7m phenylbutazone concentrations. Thyroid peroxidase activity was measured by tyrosine-iodinase, triiodide and guaiacol assays. Soluble, pseudosolubilized and crude peroxidase preparations from bovine glands, as well as the soluble enzyme from human thyroids, have shown inhibition of tyrosine-iodinase activity when incubated with phenylbutazone in concentrations ranging from 10\m=-\3m to 10\m=-\8m, with a Ki of 4 \m=x\10\m=-\6m for bovine thyroid peroxidase and of 6 \m=x\10\m=-\6m for human soluble peroxidase. Formation of triiodide was affected between 10\m=-\3m and 10\m=-\8m phenylbutazone concentrations. Guaiacol peroxidation was scarcely affected by the action of the drug. We have concluded that phenylbutazone affects the intrathyroidal iodine metabolism through the inhibition of thyroid peroxidase in concentrations which are usually present in the sera of patients treated with this drug. Some patients treated with phenylbutazone have