Clinical meaning
Differentiated thyroid cancer (DTC) includes papillary thyroid carcinoma (PTC — 80-85% of all thyroid cancers, excellent prognosis) and follicular thyroid carcinoma (FTC — 10-15%, slightly more aggressive with hematogenous metastases). After total thyroidectomy ± radioactive iodine (RAI) ablation, surveillance relies primarily on serum thyroglobulin (Tg) — a protein produced exclusively by thyroid follicular cells (normal and malignant). After complete thyroidectomy and RAI ablation, Tg should be undetectable (<0.2 ng/mL on sensitive assay) because no thyroid tissue remains. A RISING Tg indicates persistent or recurrent disease. Tg interpretation requires understanding of thyroglobulin antibodies (TgAb): present in 20-25% of DTC patients, TgAb interfere with immunometric Tg assays, producing falsely LOW Tg results — a rising TgAb trend may itself indicate recurrence even when Tg appears suppressed. Stimulated Tg testing (either by TSH withdrawal — stopping levothyroxine for 3-4 weeks to allow TSH to rise >30 mIU/L, or by recombinant human TSH/Thyrogen injection) increases the sensitivity of Tg measurement — a stimulated Tg <1 ng/mL in the absence of TgAb has a negative predictive value >98% for disease-free status. The ATA risk stratification system guides surveillance intensity: low risk (intrathyroidal DTC, ≤5 lymph nodes with micrometastases, no vascular invasion → excellent prognosis, 1-3% recurrence), intermediate risk (microscopic extrathyroidal extension, >5 lymph nodes, vascular invasion, aggressive histology → 5-20% recurrence), high risk (macroscopic invasion, incomplete resection, distant metastases → >20% recurrence).