8465 Diagnostic Conundrum: The Mystery of Metastatic Papillary Thyroid Cancer with Persistently Elusive Thyroglobulin

Abstract Disclosure: P. Vemparala: None. M. Bollineni: None. Introduction- Among endocrine malignancies, differentiated thyroid cancers account for the majority with most of them boasting a favorable prognosis. Thyroglobulin, a pivotal biochemical marker, aids in detecting recurrence or persistent disease when combined with neck ultrasound, I-131 scintigraphy, and FDG PET scans. Anti-thyroglobulin antibodies, found in a quarter of cases, can falsely lower serum thyroglobulin levels in immunometric assays. Our intriguing case features a patient with metastatic papillary thyroid cancer, yet thyroglobulin levels persistently eluded detection. CASE PRESENTATION- A 33-year-old female presented initially to an outside facility with neck swelling, leading to a diagnosis of a 4 x 3 cm papillary thyroid cancer (PTC) in the right lobe and a 0.5 x 0.5 cm focus of PTC in the left lobe, accompanied by capsular extension, malignant cells in the left lobe margin, and lymphovascular invasion. After total thyroidectomy and lymph node exploration, radioactive iodine scan detected disease in right-sided lymph nodes, treated subsequently with radioactive iodine ablation. Two years later, she presented to our clinic with neck swelling, voice changes, and fatigue. Thyroglobulin level was measured which returned at <0.1 ng/ml, however thyroglobulin antibodies were elevated at 292 IU/ml, albeit decreased from a value of 431.5 IU/ml at initial diagnosis. Elevated thyroglobulin antibodies complicated interpretation, prompting liquid chromatography-mass spectrometry (LC-MS) for accurate measurement of thyroglobulin, which returned at <0.5 ng/ml. Ultrasound indicated metastatic disease in right cervical lymph nodes, confirmed by fine needle aspiration. In-office ultrasound-guided FNA of additional nodes validated metastasis. Modified radical neck dissection revealed metastatic PTC in 7 out of 34 lymph nodes. Surprisingly, thyroglobulin levels remained <0.5 ng/ml, pre- and post-operatively. Referred for radioactive iodine ablation, her complex journey underscored the challenges in monitoring thyroid cancer recurrence or persistent disease with thyroglobulin levels even by methods such as mass spectrometry. Conclusion- Key learnings from this case highlight the importance of cognizance in utilizing thyroglobulin levels to guide adjuvant therapy decisions and for postoperative monitoring in high risk patients, as low levels do not rule out recurrence or persistence. Anti-thyroglobulin antibodies pose challenges, necessitating techniques like LC-MS. Finally, recognizing “nonsecretor” thyroid cancers, an aggressive subgroup with poorer prognosis, is vital as they often present with low or undetectable thyroglobulin levels. Presentation: 6/2/2024