The studies proposed here are planned with a view to contribute to the understanding of thyroid gland physilogy in health and its alterations in diseases of the thyroid as well as of other organs systems. We have recently observed in tissues of man and the rat an inhibitor of binding of thyroid hormones to serum proteins and an inhibitor of phagocytosis of Escherichia Coli by polymorphonuclear leucocytes. Thyroid hormone binding inhibitor (THBI) is also present in serum of patients with nonthyroid illnesses (NTIs). We shall characterize and isolate the THBI and the phagocytosis inhibitor (PI) in the tissues, determine if the two inhibitors are the same or distinct, estimate quantitatively the release of THBI and PI into the circulation of patients with NTIS, study in NTI patients the correlation of serum levels of the inhibitors with laterations in thyroid hormone levels, with severity of NTI, and with mortality. Other studies proposed here deal with i) the nature, sources and biological significance of iodothyronines and their derivatives in health, ii) the nature, basis and significance of changes in metabolism of iodothyronines. More specifically, we shall develop RIAs of 3-monoiodothyronine (3-T1) and thyronine (To) and study their metabolism. We shall examine whether measurements of urinary excretion of To, the ultimate product of iodothyronine metabolism, reflect overall thyroidal secretion of iodothyronines. We shall determine relative effects of various thyroid analogs on iodothyronine monodeiodinases in the tissues to investigate whether or not there is selectivity in the effects of iodothyronines on various tissues. In other studies, we shall investigate the usefulness of iodinated radio-contrast agents, e.g. sodium ipodate (Oragrafin R), which inhibit extrathyroidal monodeiodination of T4 to T3, in the management of hyperthyroidism.
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