Thyroglobulin (Tg) is a protein produced exclusively by the follicular cells of the thyroid gland, the butterfly-shaped organ located in the neck. Its main purpose is to serve as the structural framework for the synthesis and storage of the thyroid hormones, T3 and T4. Measuring the concentration of this protein in the blood provides information about the amount of thyroid tissue present.
The Function of Thyroglobulin
Thyroglobulin is a large glycoprotein that acts as a scaffold where iodine is attached to create the thyroid hormones. Inside the thyroid gland’s follicles, Tg is stored in a substance called colloid, where it holds multiple tyrosine residues. These residues become iodinated and chemically coupled to form the inactive versions of thyroxine (T4) and triiodothyronine (T3) within the Tg molecule.
When the body requires thyroid hormone, TSH prompts the follicular cells to break down the Tg molecule. This process releases the active T4 and T3 hormones into the bloodstream to regulate metabolism, growth, and development. Since Tg is contained within the thyroid, only a tiny amount normally “leaks” into the circulation, which is what the blood test measures. The level of Tg correlates with the total mass of thyroid tissue present.
What Is Considered a Normal Level
For an individual with an intact thyroid gland, the thyroglobulin reference range typically falls between approximately 1.5 and 40 nanograms per milliliter (ng/mL). The exact range can vary significantly between laboratories and the specific testing method used. Because Tg levels are proportional to the amount of thyroid tissue, a normal result reflects a healthy, functioning gland. One gram of normal thyroid tissue is roughly equivalent to 1 ng/mL of Tg in the serum.
Tg levels can fluctuate based on the size of the gland and the level of stimulation it receives from TSH. Elevated Tg levels are not necessarily a sign of cancer, as many benign conditions can cause an increase. Conditions that cause inflammation or over-activity, such as thyroiditis, Graves’ disease, or benign thyroid nodules, can all lead to a higher Tg reading. Thyroid hormone treatment that suppresses TSH can also lower the Tg level in people with an intact gland.
Interpreting Levels After Thyroidectomy
The measurement of thyroglobulin becomes most informative after a total thyroidectomy, the surgical removal of the thyroid gland. Since Tg is only produced by thyroid tissue, the goal after this procedure is for the Tg level to be extremely low or undetectable. The absence of measurable Tg suggests that all normal and cancerous thyroid tissue has been successfully removed.
In this “athyrotic” state, the target Tg level is often less than 0.2 ng/mL, or ideally, completely undetectable. A level below 0.1 ng/mL indicates a minimal risk of cancer recurrence. Thyroglobulin is used as a surveillance marker, and any detectable or rising level suggests the presence of residual thyroid tissue or a recurrence of thyroid cancer.
Monitoring is often performed using two types of tests: suppressed and stimulated Tg. Suppressed Tg is measured while the patient is taking thyroid hormone medication, which keeps TSH low. The stimulated test involves temporarily stopping the thyroid medication or administering recombinant human TSH to intentionally raise the TSH level. Because TSH stimulates all thyroid cells, a stimulated Tg test can reveal small amounts of residual or recurrent cancer tissue that might not be detectable under suppressed conditions. A stimulated Tg level below 1.0 ng/mL is associated with being tumor-free.
Why Thyroglobulin Antibody Status Matters
Thyroglobulin Antibodies (TgAb) are proteins produced by the immune system that mistakenly target the body’s own thyroglobulin. These antibodies are present in a portion of the population, particularly those with autoimmune thyroid conditions like Hashimoto’s or Graves’ disease. When a patient’s blood contains TgAb, it can directly interfere with the laboratory test used to measure the Tg protein.
The presence of these antibodies can cause the reported Tg value to be falsely low or even undetectable. This is a problem because it can mask the presence of residual or recurrent thyroid cancer in a patient who has had a thyroidectomy. For this reason, the TgAb level must always be measured simultaneously with the Tg level to assess the reliability of the result.
If the TgAb test is positive, the Tg measurement is considered unreliable, and doctors must rely more heavily on other monitoring tools, such as neck ultrasound, to check for cancer recurrence. While newer testing methods, like mass spectrometry, are less susceptible to this interference, the presence of TgAb still complicates interpretation. A persistently positive or rising TgAb level, even without a clear Tg reading, can sometimes be an indicator of active disease.