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False Positives in Thyroglobulin Determinations Due to the Presence of Heterophile Antibodies: An Underrecognized and Consequential Clinical Problem
Institution:1. Thyroid Unit, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts;2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Abstract:ObjectiveTo report a case series of thyroid cancer patients in whom false positive results in immunometric assays for thyroglobulin (TgIMA) were caused by heterophilic antibody interference, describe the clinical scenario in which this interference should be suspected, and recommend methods to demonstrate the interference.MethodsThree patients with unexpectedly elevated thyroglobulin results (range, 1.6-75 ng/mL) were studied. In the first patient, thyroglobulin was elevated despite the presence of Tg antibody. In the second patient, suppressed thyroglobulin was higher than a recent stimulated thyroglobulin. In the third patient, thyroglobulin became detectable years after treatment and did not change after thyroid-stimulating hormone stimulation. TgIMA concentration determination was compared to determination by a mass spectrometry method (TgMS). Thyroglobulin was also remeasured after preabsorption with heterophile antibody blocking reagents and after serial dilutions.ResultsIn all cases, thyroglobulin was undetectable by TgMS. In 2 of 3 patients, dilutions provided nonlinear thyroglobulin results. After blocking agent preabsorption, thyroglobulin dropped by 35%, 45%, and 91% in the 3 samples.ConclusionFalse positive thyroglobulin concentrations from heterophilic antibody interference have significant impact on the management of thyroid cancer. Here we show that TgMS assays can be used to rule out heterophilic antibody interference. This interference should be suspected when a detectable thyroglobulin by TgIMA does not respond to thyroid-stimulating hormone or is discordant from the clinical assessment.
Keywords:heterophilic antibody  human anti-mouse antibody  immunoassays  mass spectrometry  thyroglobulin  thyroid cancer  HA"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"heterophile antibody  IMA"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"immunometric assay  Tg"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"thyroglobulin  TgAb"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"thyroglobulin antibody  TgMS"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"thyroglobulin liquid chromatography-mass spectrometry  TgRIA"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"thyroglobulin radioimmunoassay  TSH"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"thyroid-stimulating hormone
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