8584 Quite High Thyroglobulin Levels in Thyroid Cancer in the Absence of Structural Lesion: Lab Interference or Microscopic Disease with Elevated Thyroglobulin?
Authors: Waseem Ahmad Malik , Paravastu Mounika , Pauline Calimag Angela , Arshad Bushra , Chaiban Joumana T 
Published: October 2024

Abstract
Disclosure: M. Ahmad: None. A.P. Calimag: None. B. Arshad: None. J.T. Chaiban: None.
Introduction: Thyroglobulin (Tg) is standard practice for follow-up of differentiated thyroid cancer (TC). Due to existence of thyroglobulin antibodies (Tg Ab) and Heterophile antibodies, Tg immunometric assays may be subject to interference. We present 2 challenging cases of TC with elevated Tg with absence of structural disease. Both tested positive for Epstein-Barr virus antibodies to viral capsid antigen (EBV anti VCA ab). DESCRIPTION: Case 1: 70 y.o Pt found to have calcified thyroid nodule on CT cervical spine. Thyroid ultrasound (U/S) revealed a left thyroid nodule- FNA being papillary thyroid cancer (PTC) with Bethesda 6. She had total thyroidectomy and central left lateral neck dissection. Pathology revealed PTC with 3/14 l.nodes +ve for cancer. Her Tg was 40.5 (1.2 - 35.0 ng/mL) 6 days after surgery, she received 100 mCi of radioactive Iodine (RAI). Subsequent WBS showed uptake in thyroid bed only. On follow ups, Tg started to rise persistently. PET CT unremarkable and her commensurate unstimulated Tg was 12. PET CT with interval development of a hypermetabolic focus in the postsurgical bed of thyroid and hypermetabolic cervical l.nodes. She received 100 mCi RAI + WBS that was negative for recurrence. Her Tg transiently improved but then was persistently elevated in the range 8.1-11.6 ng/ml on multiple checks. Repeat thyroid U/S did not show residual disease. Her Tg antibodies (Tg Ab) as well as Heterophile Antibody and HAMA were negative. Tg by LC-MS, was elevated in the range of 7.5 to 10.8 ng/ml. EBV anti VCA ab, IgG were positive. Case 2: 76 y.o lady initially diagnosed with toxic compressive goiter, found to have follicular thyroid cancer (FTC) after total thyroidectomy: a 5.5 cm FTC with minimal capsular/lymphatic invasion, no extrathyroidal extension, and negative margins. She received 103.7 mCi RAI after surgery. Subsequent WBS showed uptake only in the thyroid bed. Postoperatively Tg levels decreased to the range 1.6 to 5.1 ng/ml. Follow-up WBS a year later was unremarkable, and the Tg started to rise. CT scan of the chest and neck were negative. Tg by LC-MS was elevated in the range 1.6-9.2 ng/ml. PET CT was negative. Tg Ab as well as Heterophile Antibody and HAMA were negative. She tested positive for EBV anti VCA ab, IgG as well. Conclusion: Both case were elderly females- almost similar age, one with PTC and one with FTC- that had excellent structural response, but incomplete biochemical response. Measurement of Tg by LC-MS is recognized as an accurate method for Tg quantification. LC-MS assays are based on peptide quantitation after tryptic digestion which itself can have limitations due to existence of abnormal polymorphic tumor thyroglobulin (for which not much literature is available). The elevated Tg could be related to assay interference from EBV anti VCA ab (a cause or coincidence!?) or a possibility of persistent microscopic disease, hence longitudinal follow up of patients is important.
Presentation: 6/2/2024