Tumor Markers for Thyroid Cancer
Yes, there are specific tumor markers for thyroid cancer, but they vary by cancer type: thyroglobulin (Tg) is highly specific for differentiated thyroid carcinomas (papillary and follicular), while calcitonin is the specific marker for medullary thyroid cancer.
Differentiated Thyroid Cancer (Papillary and Follicular)
Thyroglobulin as the Primary Marker
- Thyroglobulin is a very specific marker for papillary and follicular thyroid carcinoma 1
- Tg is particularly valuable for post-treatment surveillance after total thyroidectomy and radioiodine ablation, where it serves as a sensitive indicator of residual or recurrent disease 1
- After complete thyroid ablation, thyroglobulin levels should be undetectable, and any rising levels indicate possible recurrence 1
Critical Limitations of Thyroglobulin
- Thyroglobulin measurement is of little help in the initial diagnosis of thyroid cancer and should not be used as a diagnostic tool for thyroid nodules 1
- Anti-thyroglobulin antibodies (TgAb) interfere with Tg measurement in approximately 15-25% of patients, rendering the test unreliable in these cases 2, 3, 4
- Tg secretion is TSH-dependent, so interpretation requires knowledge of current TSH levels 3
- Trauma to the thyroid (surgery, biopsy, radioiodine treatment) causes transient Tg elevation unrelated to malignancy 3
- False-negative results can occur: some patients with documented recurrent disease have undetectable serum Tg without antibody interference 5
Practical Monitoring Approach
- Serial Tg measurement should replace whole-body radioiodine scintigraphy for long-term surveillance 1
- Always measure TgAb simultaneously with Tg to identify potential interference 3, 4
- Persistently high or increasing TgAb levels with low Tg can indicate recurrence or persistent disease 4
- In patients with suspected recurrence but negative Tg, supplement with radioiodine scanning and radiological imaging 5
Medullary Thyroid Cancer
Calcitonin as the Specific Marker
- Serum calcitonin is a reliable and specific tool for diagnosing medullary thyroid cancer, which comprises 5-7% of all thyroid cancers 1
- Calcitonin has higher sensitivity than fine-needle aspiration cytology for detecting medullary thyroid cancer 1, 6
- Calcitonin measurement should be an integral part of the diagnostic evaluation of thyroid nodules 1
Calcitonin-Guided Management
- For calcitonin levels >150 pg/mL, the risk of metastases outside the neck is substantially higher, warranting imaging of neck, chest, and abdomen 1
- Carcinoembryonic antigen (CEA) serves as a complementary marker for medullary thyroid cancer surveillance 1
- Calcitonin doubling time <12 months indicates more aggressive disease 1
Immunohistochemical Markers for Tissue Diagnosis
- Thyroid transcription factor-1 (TTF-1) is positive in most thyroid carcinomas and helps distinguish thyroid origin from other CK7-positive tumors 1
- Thyroglobulin immunostaining on tissue samples is highly specific for differentiated thyroid carcinoma (papillary and follicular) 1
- Various immunohistochemical markers can be used on cytological samples to differentiate papillary thyroid carcinoma from other types, though none are specific enough for definitive cytological diagnosis 1
Common Pitfalls to Avoid
- Do not use thyroglobulin for initial diagnosis of thyroid nodules—it is a post-treatment surveillance marker only 1
- Never interpret Tg results without simultaneously checking for TgAb interference 3, 4
- Do not rely solely on Tg in patients with suspected recurrence; use complementary imaging when clinical suspicion is high 5
- Recognize that assay-specific differences exist for Tg measurement, so patients should be monitored with the same assay over time 3
- Do not overlook calcitonin measurement in the initial evaluation of thyroid nodules, as it is more sensitive than FNAC for medullary cancer 1