Influence of Heparin on Serum Free Thyroxine1

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Abstract
Significant elevations of the serum total free thyroxine (TfT4)4 observed in 12 patients undergoing hemodialysis stimulated further investigation of the cause of this phenomenon. Single intravenous heparin injections were administered to 9 euthyroid subjects and 5 hypothyroid patients. In both groups there was a prompt elevation of the serum TfT4 up to 5 × control values within 2 to 15 min of injecting a heparin dose of 1–50 mg. Similar concentrations of heparin in vitro did not alter the TfT4. There were only minimal and inconsistent changes in serum T4, TBG and TBPA capacities and T3 resin uptake. The heparin-induced elevation of the plasma FFA was blocked by the intravenous administration of protamine sulfate 5 min prior to the heparin in 4 control subjects; however, the rise in the TfT4 was not inhibited. Intravenous epinephrine elevated plasma FFA but did not affect TfT4 levels. We were unable to transfer any active factor in heparinized plasma capable of elevating the PfT4 of control serum in vitro. The mechanism by which heparin induces elevation of the TfT4 is not clear. Since the reaction occurred in an athyreotic subject on replacement hormone, it is independent of the thyroid gland. The increased TfT4 does not result from displacement of thyroxine from thyroxine-binding proteins by plasma FFA. The heparin molecule itself (in vivo but not in vitro) or some other substance stimulated by heparin may compete with thyroxine for these binding sites or may affect the thyroxine-TBP bond.

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