From the Guidelines
Thyroglobulin testing by reflex mass spectrometry is highly reliable for monitoring patients with differentiated thyroid cancer who have negative conventional thyroglobulin results, offering improved sensitivity and ability to detect residual or recurrent disease. This advanced testing method can detect thyroglobulin at levels as low as 0.1-0.2 ng/mL, which is approximately 10 times more sensitive than standard immunoassays 1. For patients with a history of differentiated thyroid cancer who show negative results on conventional thyroglobulin tests, mass spectrometry can detect residual or recurrent disease that might otherwise be missed.
Key Considerations
- The improved reliability of mass spectrometry stems from its ability to overcome the limitations of immunoassays, particularly interference from anti-thyroglobulin antibodies which can cause false negative results 1.
- Approximately 25-30% of thyroid cancer patients develop these antibodies, making mass spectrometry a valuable tool in this population.
- When implementing this testing, clinicians should still consider the complete clinical picture, including ultrasound findings and other imaging results, as no single test provides perfect accuracy.
- Regular monitoring using mass spectrometry-based thyroglobulin testing every 6-12 months is recommended for high-risk patients with negative conventional results to ensure early detection of disease recurrence.
Clinical Application
- For patients with basal serum Tg ≤0.1 ng/ml and unremarkable neck US, mass spectrometry may not be necessary as the negative predictive value (NPV) is 100% 1.
- However, when basal serum Tg is >0.1 ng/ml but <1.0 ng/ml, mass spectrometry may still be informative in detecting residual or recurrent disease.
- Clinicians should weigh the benefits of mass spectrometry against the potential risks of unnecessary testing and treatment, and consider the individual patient's risk profile and clinical presentation when making decisions about testing and follow-up 1.
From the Research
Reliability of Thyroglobulin by Reflex Testing using Mass Spectrometry
- The reliability of thyroglobulin by reflex testing using mass spectrometry in patients with a history of differentiated thyroid cancer and negative thyroglobulin is supported by studies that highlight the limitations of traditional immunoassays 2.
- Traditional immunoassays, such as radioimmunoassays (RIA) and immunometric assays (IMA), are limited by analytical interferences from anti-thyroglobulin autoantibodies (TgAb) and heterophile antibodies (HAb) 2.
- Thyroglobulin mass spectrometry assays have been introduced as a solution to the interference problems observed in immunoassays, but their analytical sensitivity is inferior to high sensitivity immunoassays 2.
- The use of mass spectrometry assays can help to improve the accuracy of thyroglobulin measurements, particularly in patients with negative thyroglobulin and a history of differentiated thyroid cancer 2.
Clinical Applications and Limitations
- The clinical applications of thyroglobulin measurements in the management of patients with differentiated thyroid cancer are well established, but the limitations of traditional assays must be considered 3, 4, 5.
- The presence of TgAb can interfere with thyroglobulin determination, and additional studies are necessary to rule out persistent or recurrent disease in these patients 6.
- Neck ultrasonography (US) and other imaging modalities, such as PET/CT, can be used in conjunction with thyroglobulin measurements to improve the detection of recurrent disease 3, 4, 5.
Future Directions
- Further studies are needed to evaluate the clinical utility of thyroglobulin mass spectrometry assays in patients with differentiated thyroid cancer and negative thyroglobulin 2.
- The development of new assays and technologies, such as liquid chromatography/tandem mass spectrometry, may help to improve the accuracy and sensitivity of thyroglobulin measurements 6, 2.