The main method for the treatment of differentiated thyroid carcinomas (a cancer of the thyroid gland) is total or near-total thyroidectomy (surgical removal of the thyroid) followed by radioactive iodine therapy (iodine-131) and treatment with thyroid hormones (mainly thyroxin). The metastatic disease of this thyroid carcinoma or spread of the tumour includes local recurrence and distant metastases. Metastatic disease is a factor that worsens prognosis of patients with differentiated thyroid carcinoma. After surgery or as the primary treatment, located metastases should, if possible, be removed by an experienced surgeon. For unremovable metastases which can gather radioiodine, iodine-131 therapy is an accepted procedure.

Differentiated thyroid carcinoma is typically able to produce thyroglobulin, the protein in the thyroid gland from which the thyroid hormones thyroxine and triiodotyrosine are synthesized, and gather radioiodine. Thyroglobulin is produced only by thyroid cells. If all normal and malignant thyroid tissue is successfully removed, any thyroglobulin subsequently detected in a patient with differentiated thyroid carcinoma is thought to be the product of recurrent malignancy. Thus, radioiodine diagnostic whole-body scanning and measurement of serum thyroglobulin levels are the two main methods for detecting metastatic disease of differentiated thyroid carcinoma. Undetectable thyroglobulin levels with negative radioiodine whole body scan suggest complete remission, whereas detectable or elevated thyroglobulin is associated with the presence of radioiodine uptake in local or distant metastases.

Up to now, to treat or not to treat these patients who have thyroglobulin positive and radioactive iodine negative metastases with radioiodine remains controversial. Some doctors advocate blind iodine-131 treatment for thyroglobulin positive and radioactive iodine negative metastases. Radioiodine therapy may be especially justified in patients with higher thyroglobulin levels (greater than 10 mg/L) and negative iodine-131 whole body scan and who are at high risk of any recurrence. However, high-dose radioactive iodine therapy is not without risk; especially an increased prevalence of cancers of the bladder, salivary gland, colon and female breast has been reported.

Unfortunately, no firm evidence from randomised or prospective controlled trials for or against radioiodine treatment for differentiated thyroid carcinoma with thyroglobulin positive and radioactive iodine negative metastases could be found. Further prospective controlled trials of high-quality and large scale are needed to guide clinical practice.