Follow-up Protocol for Differentiated Thyroid Cancer Post-Thyroidectomy and RAI Using Thyroglobulin
Serum thyroglobulin (Tg) and neck ultrasound (US) are the mainstays of follow-up for patients with differentiated thyroid cancer (DTC) after thyroidectomy and radioactive iodine (RAI) ablation, with monitoring frequency determined by the patient's risk stratification and response to initial treatment. 1
Initial Follow-up Assessment (6-18 months post-treatment)
- The first comprehensive assessment should be performed 6-18 months after initial treatment to evaluate response to therapy 1
- This assessment includes:
- Serum Tg measurement (on levothyroxine therapy)
- Serum Tg antibodies (TgAb) measurement
- Neck US 1
- For patients who underwent total thyroidectomy and RAI ablation, a basal serum Tg level <0.2 ng/mL on thyroid hormone therapy or <1 ng/mL after TSH stimulation indicates excellent response to therapy 1
- High-sensitivity Tg assays (<0.2 ng/mL) can be used to verify absence of disease without the need for TSH stimulation 1, 2
Risk Stratification-Based Follow-up
Low-Risk Patients with Excellent Response
- If initial assessment shows excellent response (undetectable Tg, negative neck US):
Intermediate-Risk Patients with Excellent Response
- Serum Tg and TgAb every 12-24 months
- TSH can be maintained at 0.5-2 μIU/mL
- Optional repeat neck US after 3-5 years 1
High-Risk Patients with Excellent Response
- Serum Tg and TgAb every 6-12 months
- TSH should be maintained at 0.1-0.5 μIU/mL
- Neck US every 6-12 months 1
Patients with Biochemical Incomplete Response
- Serum Tg and TgAb every 3-6 months
- TSH should be maintained <0.1 μIU/mL
- Neck US and additional imaging based on Tg/TgAb trend 1
- Rising Tg or TgAb levels warrant more intensive surveillance and consideration of additional imaging 1, 3
Patients with Structural Incomplete Response
- Serum Tg and TgAb every 3-6 months
- Repeat neck US/imaging every 3-6 months
- TSH should be maintained <0.1 μIU/mL 1
Interpretation of Thyroglobulin Results
- Important caveat: Tg levels may continue to decline for several years after initial treatment without additional therapy 4
- In patients with 6-month suppressed serum Tg of 1-5 ng/mL, 54% eventually develop suppressed Tg <1 ng/mL without additional therapy 4
- A post-thyroidectomy pre-ablation Tg level <10 ng/mL is associated with low probability of persistent disease (negative predictive value of 89%) 5
- Be aware: A transient increase in Tg levels can occur 7 days post-RAI ablation (up to 13-fold) due to thyroid tissue destruction/inflammation, which typically resolves by 6 months 6
Monitoring Considerations
- Concomitant assessment of TgAb is mandatory with every Tg measurement, as these antibodies can interfere with Tg assays causing false-negative or false-positive results 1
- To minimize variability, Tg levels should ideally be measured with the same assay throughout follow-up 1
- Short Tg doubling time (<1 year) is associated with poor outcomes and should prompt more comprehensive imaging evaluation 1
- In patients with detectable Tg but negative imaging (indeterminate or biochemical incomplete response), the positive predictive value for recurrence increases with higher Tg levels or with levels that increase over time 1
Imaging in Follow-up
- Neck US is the first-line imaging investigation for DTC after initial therapy 1
- Whole-body scintigraphy (WBS) is not utilized in low-risk patients without suspicion for recurrence and normal thyroid US 1
- FDG-PET/CT scanning is not recommended for routine surveillance if there is no evidence of residual disease 1
- Additional cross-sectional imaging should be considered if Tg or TgAb levels are rising 1
By following this protocol, clinicians can effectively monitor patients with differentiated thyroid cancer after thyroidectomy and RAI ablation, detecting recurrence early while avoiding unnecessary testing in patients with excellent response to initial therapy.