What blood tests are appropriate for diagnosing and monitoring thyroid cancer?

Blood Tests for Thyroid Cancer

Critical Distinction: Diagnosis vs. Monitoring

Thyroid function tests (TSH, free T4, free T3) do not diagnose thyroid cancer and should not be ordered for this purpose 1, 2. These tests measure hormone production capacity, not malignancy—thyroid cancer commonly coexists with completely normal thyroid function 1.

Diagnostic Phase Blood Tests

For Differentiated Thyroid Cancer (Papillary/Follicular)

• TSH should be obtained during initial nodule workup, though it has limited diagnostic value for detecting malignancy itself 2
• Thyroglobulin (Tg) measurement is NOT helpful for initial diagnosis and should not be performed 2, 3
• Serum calcitonin should be measured as part of the diagnostic evaluation to rule out medullary thyroid cancer, as it has higher sensitivity than fine needle aspiration for this subtype 2

For Medullary Thyroid Cancer

• Basal serum calcitonin is the essential diagnostic marker 4, 3, 5
• Carcinoembryonic antigen (CEA) should be measured 4
• Calcium and plasma metanephrines/normetanephrines (or 24-hour urine collection) to screen for pheochromocytoma in multiple endocrine neoplasia syndromes 4

Post-Treatment Monitoring Blood Tests

First Assessment (2-3 Months Post-Surgery)

Purpose: Verify adequate levothyroxine suppressive therapy only 4, 1, 2

• TSH, free T4, free T3 to confirm appropriate dosing 4, 1, 2
• No tumor marker testing at this timepoint 4

Second Assessment (6-12 Months Post-Treatment)

Purpose: Determine disease-free status 4, 2

For differentiated thyroid cancer:

• Basal serum thyroglobulin (Tg) on levothyroxine therapy 4, 2
• rhTSH-stimulated serum Tg (or after levothyroxine withdrawal) 4, 2, 6
• Anti-thyroglobulin antibodies (TgAb) measured concurrently, as 25% of patients have interfering antibodies 2, 7, 3
• Undetectable stimulated Tg (<1.0 ng/ml) with negative TgAb and normal neck ultrasound indicates complete remission with <1% recurrence risk at 10 years 4, 2

For medullary thyroid cancer:

• Calcitonin and CEA monitoring should both be included 4

Long-Term Follow-Up (Annual)

For patients in complete remission:

• Basal serum Tg on levothyroxine therapy measured annually 4, 2
• TSH to monitor adequacy of thyroid hormone replacement 4, 2
• TgAb measured concurrently with Tg 4, 7, 3

For medullary thyroid cancer:

• Calcitonin and CEA every 6 months initially, then annually 4

TSH Suppression Targets Based on Risk

The target TSH level varies by risk stratification 4, 1:

• High-risk or persistent disease: TSH <0.1 mIU/L 4, 1
• Intermediate-risk with biochemical incomplete/indeterminate response: TSH 0.1-0.5 mIU/L 4, 1
• Low-risk with excellent response: TSH 0.5-2 mIU/L 4, 1

Critical Pitfalls to Avoid

• Never rely on basal Tg alone without TSH stimulation for the initial 6-12 month assessment—stimulated Tg is far more sensitive for detecting residual disease 2, 6
• Always measure TgAb concurrently with Tg, as antibodies interfere with Tg measurement and can themselves indicate disease when rising 4, 2, 7, 3
• Do not use Tg for initial diagnosis of thyroid nodules—it has no diagnostic value in this setting 2, 3
• Isolated Tg measurements cannot be reliably interpreted in the presence of normal thyroid tissue; trend over time is more valuable 4
• Rising TgAb levels with low Tg can indicate recurrence or persistent disease 4, 7
• Moderately elevated Tg may result from inadequate TSH suppression rather than disease recurrence 8

Highly Sensitive Tg Assays

• High-sensitivity Tg assays (<0.2 ng/ml functional sensitivity) can be used instead of TSH-stimulated Tg testing to verify absence of disease in patients with excellent response 4, 2
• Assays with functional sensitivity 0.2-0.3 ng/ml achieve 54-63% sensitivity and 89% specificity for basal Tg on levothyroxine 6
• Ultra-sensitive assays may provide earlier indication of Tg presence and allow trend monitoring without TSH stimulation, though at potential cost of lower specificity 4, 6