Thyroglobulin is the protein precursor of thyroid hormone and is made by normal well differentiated benign thyroid cells or thyroid cancer cells. Although thyroglobulin levels may be elevated in patients with thyroid cancer, a large number of benign thyroid conditions may also be associated with elevated levels of thyroglobulin, hence an increased thyroglobulin alone in a patient not known to have thyroid cancer is not a sensitive or specific test for the diagnosis of thyroid cancer. Simply examining the thyroid or carrying out a thyroid biopsy can produce significant elevations in the circulating blood level of thyroglobulin. Similarly, patients with thyroid inflammation can have very high levels of thyroglobulin. Patients without a known diagnosis of thyroid cancer do not generally benefit from having the levels of thyroglobulin measured. Some patients with antithyroglobulin antibodies may have inaccurate thyroglobulin levels measured in the lab if the antibodies interfere with the assay, but this is uncommon.

Since thyroglobulin is normally only made by thyroid cells, it serves a useful readout for the presence or absence of thyroid cells, particularly in patients with thyroid cancer where it serves as a "tumor marker". In patients with a known diagnosis of well differentiated thyroid cancer (most types of papillary and follicular disease), the serum thyroglobulin (Tg) is a useful ancillary marker of disease activity and provides information about the state and extent of residual functioning thyroid tissue in patients both on and off L-thyroxine suppression or after stimulation with recombinant TSH. Ideally, the thyroglobulin levels will be low or undetectable after treatment (usually surgery followed by radioactive iodine). 

There are certain pitfalls to the interpretation of thyroglobulin levels, which may include assay variability and the presence of thyroglobulin antibodies. For an overview of the thyroglobulin test in the management of thyroid cancer, see Thyroid 1999 May;9(5):435-41 Detection of residual and recurrent differentiated thyroid carcinoma by serum thyroglobulin measurement.

It is possible that the development of more sensitive Thyroglobulin assays will reduce the need for TSH-stimulated thyroglobulin testing Serum Basal thyroglobulin measured by a second-generation assay correlates with the recombinant human thyrotropin-stimulated thyroglobulin response in patients treated for differentiated thyroid cancer Thyroid. 2010 Jun;20(6):587-95.