Recurrent differentiated thyroid cancer without elevation of serum thyroglobulin

Thyroglobulin (Tg) is a reliable tumor marker in patients with well-differentiated thyroid cancer (WDTC). We identified 11 patients who had undetectable serum Tg and no thyroglobulin antibody (TgAb) in the presence of clinical disease. Three had residual disease after ablation of the thyroid by surgery plus radioiodine and 8 relapsed after a disease-free interval. Histologic review confirmed that 7 of the tumors were papillary carcinomas and 4 were follicular carcinomas. Immunohistochemical staining for Tg was positive in 6 of 7 papillary and in 3 of 4 follicular carcinomas. There were no identifiable histologic or clinical features that could be used to predict further patients who may relapse with absence of this serum marker. Negative serum Tg did not appear to be an adverse prognostic feature. During follow-up, measurement of Tg and TgAb should be supplemented by radioiodine scanning and radiological imaging in patients in whom recurrence is likely or suspected.