The lymphatic and venous pathways for the outflow of thyroxine, iodoprotein and inorganic iodide from the thyroid gland.

1. Baboons and cats were given radioactive iodine and, at varying times after the injection, samples of thyroid and non-thyroid lymph and of thyroid venous and peripheral venous blood were collected. The radioactive material in these samples was separated by paper chromatography or by differential precipitation and solvent extraction into three main fractions: inorganic iodide, iodoamino acid iodine and high molecular-weight material (retained at the origin of chromatograms and not extractable by butanol or ethanol). The latter was considered to be iodoprotein.2. Thyroxine was the main component of the radioactive iodoamino acid iodine in thyroid lymph, in thyroid venous and in peripheral blood. The concentration of thyroxine radioactivity in the thyroid lymph was several times greater than that in either thyroid venous or peripheral blood plasma, both before and after giving thyroid stimulating hormone.3. An unidentified thyronine compound that was frequently found in thyroid lymph and also in blood samples contained an appreciable proportion of the radioactive iodine. This substance was probably a metabolite of one of the iodothyronines. In addition, iodotyrosines probably accounted for up to 4% of the radioactivity in the lymph and blood samples but radioactive triiodothyronine could not be detected with certainty.4. In some experiments lymph was obtained from the cervical lymph trunk at a considerable distance from the thyroid gland, in order to avoid operative trauma to the gland. This cervical lymph contained diluted thyroid lymph but even so it contained more radioactivity in the form of iodoamino acid and iodoprotein than did peripheral blood or non-thyroid lymph. Cervical lymph and thyroid lymph both contained less radioactive inorganic iodide than did non-thyroid lymph.5. The administration of thyroid stimulating hormone caused a prolonged rise in the output of radioactive iodoamino acid in the thyroid venous blood and, for a limited period, an increase in the output of radioactive inorganic iodide. At the same time there was an increase in the output of radioactive material in the thyroid lymph. The main part of the latter was due to a rise in the output of iodoprotein.6. The lymphatics and the venous system provide alternative pathways for the outflow of iodine compounds from the thyroid gland. These pathways differ in relative importance for different iodine compounds. For iodoprotein the lymphatic pathway is the important one since there is no appreciable release of this substance into the thyroid venous blood. In the case of inorganic iodide, where there is no appreciable difference in concentration between thyroid lymph and blood, the greater flow of blood makes the venous pathway relatively more important than the lymphatic one. Thyroxine is released into the thyroid lymph in higher concentration than into the blood but the faster flow of blood makes the venous pathway relatively more important.