Spuriously elevated free thyroxine associated with autoantibodies, a result of laboratory methodology: case report and literature review.

OBJECTIVE: We describe a case of spurious hyperthyroxinemia secondary to thyroid hormone autoantibodies (THAAbs) in a clinically euthyroid patient with Turner mosaic syndrome.

METHODS: Several commonly available laboratory-based approaches were used, which indicated a disproportionate elevation of free thyroxine (T4) and ultimately led to the diagnosis of THAAbs. A literature review was undertaken to examine the clinical and laboratory associations of THAAbs.

RESULTS: The free T4 result of the patient was highly discrepant when measured using an Advia Centaur platform (5.89 ng/dL) as compared with the Vitros 5600 and DxI 800 platforms (1.03 and 0.74 ng/dL, respectively). Polyethylene glycol precipitation of the patient's sample showed reduced free T4 recovery (26%), suggesting the presence of a high-molecular-weight interfering substance. Rheumatoid factor and heterophile blocking tube studies were negative. These results suggested a presumptive diagnosis of THAAbs. Direct detection of THAAbs using a radiobinding method confirmed the diagnosis. A review of the literature showed that THAAbs are prevalent among patients with (autoimmune and nonautoimmune) thyroid disorders and nonthyroid autoimmune disorders but rarely cause spurious measurements. Possible pathogenesis includes molecular mimicry, exposure of the antigenic surfaces of iodinated thyroglobulin molecules to B lymphocytes in injurious or inflammatory conditions involving the thyroid gland. Free thyroid hormone methods using one-step analog and labeled antibody designs are prone to falsely high measurements, whereas two-step analog designs may produce spuriously low results.

CONCLUSION: THAAbs are an underrecognized cause of laboratory interference that is best approached by joint clinical-laboratory efforts. The routine laboratory techniques described above can suggest preliminary diagnosis of this rare entity.