Thyroglobulin

The thyroglobulin test (Tg; thyroid prohormone substrate) is used in the postoperative surveillance of differentiated thyroid carcinoma (papillary and follicular) to assess therapeutic response, identify persistent thyroid tissue, and detect recurrence. Results guide longitudinal management following thyroidectomy and radioiodine ablation. Measurement may be performed during thyroid-stimulating hormone suppression (TSH-suppressed Tg) and, when indicated, after exogenous TSH stimulation (TSH-stimulated Tg) to improve diagnostic sensitivity. Because anti-thyroglobulin antibodies can interfere with immunoassays, anti-Tg antibody testing is performed concurrently.

Thyroglobulin is a 660‑kDa glycoprotein stored in the follicular colloid and required for the iodination and coupling reactions that generate T4 and T3. Papillary and follicular thyroid carcinomas typically retain thyroglobulin synthesis, making serum Tg a marker for residual or recurrent disease after thyroidectomy and radioiodine ablation. Initial assessment is commonly performed 6–12 months postoperatively while TSH is suppressed; in selected cases, exogenous TSH stimulation increases sensitivity because some patients with undetectable suppressed Tg exhibit detectable concentrations after stimulation. Anti‑thyroglobulin antibodies are present in a substantial proportion of patients and can cause falsely low or undetectable Tg by assay interference; therefore, anti‑Tg antibodies should be measured in parallel. Heterophile antibodies may also interfere and can be encountered with cytomegalovirus infection, toxoplasmosis, and infectious mononucleosis. False‑negative results occur with very small tumor burden or with tumors that secrete minimal or structurally abnormal thyroglobulin. In the absence of anti‑Tg antibodies, an undetectable TSH‑stimulated Tg has a high negative predictive value for future recurrence. Interpretation is integrated with clinical examination and imaging, and follow‑up intervals are individualized by risk, often every 6 months for high‑risk disease and annually for low‑risk disease.