From the Guidelines
The cut-off value for thyrogen-stimulated thyroglobulin (Tg) concerning for thyroid cancer recurrence is generally considered to be 2 ng/mL or higher. Patients with stimulated Tg levels below 2 ng/mL typically have a low risk of recurrence, while those with levels above this threshold warrant further investigation with imaging studies such as neck ultrasound, radioiodine whole-body scan, or other cross-sectional imaging 1. This testing involves administration of recombinant human TSH (rhTSH, brand name Thyrogen) via two 0.9 mg intramuscular injections given 24 hours apart, with blood sampling for Tg measurement 72 hours after the second injection.
Key Considerations
- The 2 ng/mL threshold has been established based on clinical experience showing good sensitivity and specificity at this level 1.
- The interpretation of stimulated Tg values should always consider the individual patient's clinical context, including their initial disease stage, previous treatments, and the presence of anti-thyroglobulin antibodies which can interfere with accurate measurement.
- Some centers may use slightly different thresholds based on their assay characteristics and institutional experience.
Management Approach
- For patients with stimulated Tg levels between 2-10 ng/mL, consideration of additional nonradioiodine imaging (e.g., FDG-PET ± CT) may be necessary if radioiodine imaging is negative 1.
- For patients with stimulated Tg levels above 10 ng/mL, radioiodine therapy with 100-150 mCi, posttreatment 131I imaging may be considered 1.
- Surgery (preferred) or radioiodine treatment may be indicated for resectable locoregional recurrence 1.
From the Research
Thyrogen-Stimulated Thyroglobulin Cut-Off Levels
The cut-off level for thyrogen-stimulated thyroglobulin in the context of thyroid cancer recurrence is a critical parameter.
- Studies have proposed various cut-off levels, including:
- 5.6 ng/ml, above which the risk of relapse increases by 2.38-fold in Tg-ab negative subjects with differentiated thyroid cancer 2
- 2.0 ng/ml, which is a commonly used threshold for patients in remission 3
- 0.6 ng/ml and 2.3 ng/ml, which correspond to the 2.0 ng/ml and 10.0 ng/ml limits for THW/Tg, respectively 3
- 1 ng/ml, below which patients are considered to be at very low risk of recurrence 4
- It is essential to note that the method of stimulation, whether through levothyroxine withdrawal or recombinant human TSH (rhTSH), can impact the obtained Tg concentrations 3, 5
- The choice of assay can also influence the cut-off level, with second-generation assays providing more sensitive measurements 5
Factors Influencing Cut-Off Levels
Several factors can affect the cut-off levels, including:
- Patient risk group, with high-risk patients potentially requiring lower cut-off levels 6
- Presence of antithyroglobulin antibodies, which can interfere with Tg measurements 6
- Method of stimulation, with rhTSH-stimulated Tg potentially requiring different cut-off levels than THW-stimulated Tg 3
- Assay selection, with different assays providing varying levels of sensitivity and specificity 5