SUN-LB100 False Elevation of Thyroglobulin by Immunoassay with Negative Thyroglobulin Antibody and Measures Blocking Heterophile Antibody in a Patient Post-thyroidectomy for Papillary Thyroid Cancer; Use of Liquid Chromatography─Tandem Mass Spectrometry

Abstract

Background: Thyroglobulin (Tg) is a useful tool to monitor residual or recurrent differentiated thyroid cancer in patient post-thyroidectomy. The test is typically performed using immunoassay, which is subject to interference by thyroglobulin antibody (TgAb) and heterophile antibody (HAb). TgAb is routinely checked to validate the test result. Pre-treatment of specimen with HAb blocking agents is adopted to prevent interference by HAb. Clinical Case: A 71-year male had incidental thyroid nodules, leading to discovery of papillary thyroid cancer status post thyroidectomy. There were two sub-centimeter cancer foci, partially encapsulated without capsular or vascular invasion, and surgical margin was clear. It was classified as pT1aNxMx, without clinical evidence of lymph node or distant metastasis. Thyroid remnant ablation was not planned. Measurements of Tg (ng/mL)/TgAb (+ or -) before and after surgery were: Pre-surgery 48.7/ (-); 3M post-surgery 1.7/ (-); 6M post-surgery 450.3/ (-). Tg levels remained markedly elevated up to > 1000 ng/mL with negative TgAb upon repeats and follow-ups. The high Tg levels prompted search for thyroid tissue, either normal or cancerous. Thyroid/Neck thyroid ultrasound didn’t reveal suspicious lesion. Radioactive iodine (RAI) whole body scan showed two foci at thyroid bed, without evidence of ectopic thyroid, node or distant metastasis. The patient received 74.3 mCi I-131 treatment. After RAI treatment, Tg levels remained markedly elevated, ranging from 434.6 to 1232.1 ng/mL, all with negative TgAb. The discrepancy of clinical observations and Tg results suggested false readings of Tg assays. As TgAb had been consistently negative, assay interference by HAb was strongly suspected, but specimen pre-treated with HAb blocking agents yielded similar results. Tg measurement by liquid chromatography─tandem mass spectrometry was performed, and Tg was undetectable, < 0.5 ng/mL, confirming the clinical impression that elevated Tg levels by immunoassay were false regardless negative TgAb and pre-treatment of specimen with HAb blocking agents. Conclusion: Elevated Tg levels by immunoassay can be false even with negative TgAb and pre-treatment of specimen with HAb blocking agents. When Tg levels are inconsistent with clinical findings, Tg measurement by liquid chromatography─tandem mass spectrometry is useful to uncover the false readings before proceeding to extensive work-up and treatment. Reference: (1) Preissner, C., O’Kane, D., Singh, R., Morris, J., Grebe, S. Phantoms in the assay tube: Heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003;88:3069-74 (2) Netzel, B., Grebe, S., Algeciras-Schimnich, A. Usefulness of a thyroglobulin liquid chromatography─tandem mass spectrometry assay for evaluation of suspected heterophile interference. Clin Chem 2014;60:1016-8 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.