Heparin has been shown to affect thyroid function test results [1, 2]. Because heparin is now commonly used to treat patients with unstable angina or atrial arrhythmias, physicians should be aware of this interaction. We describe a patient with a heparin-induced increase in the serum free thyroxine level as measured by direct equilibrium dialysis and a one-step free thyroxine immunoassay.

A 62-year-old woman with diabetes mellitus, hypertriglyceridemia, and coronary artery disease presented with unstable angina. On physical examination she appeared to be euthyroid, with no palpable thyroid nodules or goiter. She began receiving intravenous heparin, and the serum free thyroxine level measured during heparin treatment using an in-house assay (Ciba Corning, Medfield, Massachusetts) was 21.9 pmol/L. Repeat measurement of free thyroxine in the same serum sample showed a level of 32.2 pmol/L; the serum thyroid-stimulating hormone level was normal at 4.2 mU/L (normal range, 0.35 to 5.5 mU/L). To determine the cause of increased free thyroxine levels, total thyroxine, free thyroxine as measured by equilibrium dialysis, and free (nonesterified) fatty acid levels were determined in available blood samples that were collected into heparin-free tubes at hospital admission before heparin treatment, during heparin treatment, and 3 days after heparin infusion. As shown in Table 1, total thyroxine levels were not affected; the serum free thyroxine level increased only while the patient was receiving heparin and returned to baseline after therapy was discontinued.

Heparin has been reported to cause an increase in free thyroxine levels in plasma when measured by direct equilibrium dialysis [1, 2]. This increase has been shown to be an in vitro artifact related to a heparin-induced increase in lipoprotein lipase activity, which thereby causes the hydrolysis of triglycerides and a subsequent increase in free fatty acid levels. The long incubation time required for the dialysis method may allow the generation of sufficiently high free fatty acid levels within the assay system to compete with or displace thyroxine from thyroxine-protein binding sites, leading to the false increase in measured free thyroxine levels [2, 3]. The effect of intravenous heparin on free thyroxine levels, as determined by nondialysis methods has been more variable [4, 5] but does not appear to cause major changes in the results of assays that do not involve long incubation periods [5]. Our patient had an increased free thyroxine serum level, even with an automated one-step immunoassay that can be completed within 15 minutes. Patients with hypertriglyceridemia may have a higher free fatty acid level while receiving heparin. This may lead to significantly elevated free thyroxine levels even with the shorter, more commonly used free thyroxine assays. A greater increase in free thyroxine levels may also be expected with samples that are not immediately assayed, a situation analogous to a prolonged incubation time. Physicians should recognize some of the limitations inherent in these assays so that misinterpreted thyroid function test results and inappropriate treatment are avoided.