Is Thyroglobulin Level by Liquid Chromatography Tandem-Mass Spectrometry Always Reliable for Follow-Up of DTC After Thyroidectomy: A Report on Two Patients

Patient 1

A 63-year-old male underwent total thyroidectomy with central neck dissection, with findings of tall-cell variant papillary thyroid cancer (PTC) and chronic lymphocytic thyroiditis. The resected lymph nodes did not show PTC, and the patient was diagnosed with Stage 2 (T2N0M0) PTC. Postoperatively, his serum thyrotropin (TSH) was 122 mIU/L off therapy with levothyroxine, his TgAbs were elevated, and Tg by LC–MS/MS was detectable. He underwent radioiodine therapy with 100 mCi of ¹³¹I. The post-therapy scan was negative. Over the next year, the Tg levels by LC–MS remained undetectable, but his TG-Abs increased. Neck US showed a right, level II, neck node, and a 8 mm hypoechoic mass in the right thyroid bed. A right, modified, neck dissection confirmed right paratracheal metastatic PTC, and metastasis to 1/55 resected lymph nodes.

Patient 2

A 32-year-old Caucasian female presented with bilateral thyroid nodules and underwent total thyroidectomy with central neck dissection. The final pathology showed a bilateral multifocal PTC, with involvement of 13 level VI lymph nodes. Consequently, she was diagnosed with Stage 3 (T3N1aM0) PTC. Postoperatively, her serum TSH was elevated at 95 mIU/L off therapy with levothyroxine, her TgAbs were elevated, and Tg by LC–MS/MS was 7.1 ng/mL She underwent radioiodine therapy with 150 mCi of ¹³¹I. The post-therapy scan showed uptake in the left neck. Four months post radioiodine therapy, the Tg level by LC–MS/MS was <0.5 ng/mL in the presence of TgAbs. Neck US showed two left cervical lymph nodes suspicious for malignancy. A left neck dissection confirmed metastatic PTC in 5/26 resected lymph nodes. Following surgery, her Tg by LC–MS/MS and IMA remained undetectable, TgAb levels continued to decrease, and neck US did not shown any new lesions in the thyroid bed or metastatic lymph nodes in the lateral neck.

Conclusion

Tg measurement by LC–MS/MS has been suggested for follow-up of DTC in patients with elevated TgAbs. The accuracy of Tg LC–MS/MS testing in the presence of TgAbs was initially validated using biochemical criteria, without testing the performance of the method in clinically defined specimens from TgAb-positive patients with structural disease (2 –4). Here, we present two patients where dependence on Tg measurements by LC–MS/MS would have led to a missed diagnosis of recurrent structural disease.

In these two patients, the TgAb levels were a more reliable tumor marker than Tg itself. The TgAb trend is a surrogate marker for monitoring DTC disease status in patients with TgAbs, and can be more reliable than the measurement of Tg (5). TgAb–Tg complexes are rapidly cleared from the blood stream. In patients with recurrent or progressive disease, TgAb levels can rise while Tg levels seem to fall and may be undetectable. This scenario has been shown in animals, and probably takes place in humans as well (6).

The patients presented here suggest that using Tg measurements by LC–MS/MS for DTC surveillance also has its limitations, and clinicians should be aware of this possibility.

Thyroid US and Tg levels should be used simultaneously for PTC surveillance, and a persistent increase in TgAbs should prompt evaluation for metastatic DTC, in accordance with the 2015 American Thyroid Association Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer (7).