Thyroglobulin: Definition


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Thyroglobulin is a protein made by the thyroid gland. The thyroid uses it to build thyroid hormones. Only thyroid cells make it, so it serves as a marker of thyroid tissue. Pathologists test for it in tissue, and doctors measure it in blood.

This article explains what thyroglobulin is, which tumors make it, how pathologists test for it, and what your report may say.

What is thyroglobulin?

Thyroglobulin is a large protein that the thyroid gland makes and stores. The thyroid gland sits at the front of the neck. It makes the hormones thyroxine (T4) and triiodothyronine (T3), which help control how the body uses energy. The gland builds these hormones on thyroglobulin.

The thyroid contains tiny round sacs called follicles. Follicular cells line each sac. They make thyroglobulin and store it inside the follicle. A small amount of thyroglobulin also reaches the blood. Blood levels roughly follow the amount of thyroid tissue in the body.

Which cells make thyroglobulin?

Follicular cells, the main cells of the thyroid, make thyroglobulin. Other cells in the gland do not make it. C cells, also called parafollicular cells, make a different hormone called calcitonin. Cells outside the thyroid do not make thyroglobulin.

Which thyroid tumors make thyroglobulin?

Tumors that start in follicular cells often continue to make thyroglobulin. This is why the protein is useful to pathologists and doctors. The pattern differs by tumor type:

How do pathologists test for thyroglobulin?

Pathologists test for thyroglobulin in tissue with immunohistochemistry. This test uses an antibody that sticks to the protein. The pathologist places the antibody on a thin slice of tissue. A color change shows which cells contain thyroglobulin, usually as brown staining. Cells that stain are positive. Cells that do not stain are negative.

The test helps most when a tumor has spread. Pathologists sometimes find a metastasis and need to determine its origin. A positive thyroglobulin stain points to the thyroid. In one large 2021 study, none of 6,403 tumors from outside the thyroid stained for thyroglobulin. The study tested 104 tumor types.

The test has limits. A tumor inside the thyroid can stain because it picks up thyroglobulin from nearby follicles. A negative stain does not rule out a thyroid origin, because some thyroid cancers stop making the protein. Pathologists read the stain together with the cell appearance and other stains.

What does the thyroglobulin blood test show?

The blood test measures how much thyroglobulin is in the blood. Doctors use it mainly to follow people treated for thyroid cancer that makes thyroglobulin. Treatment usually removes part or all of the thyroid. Some people also receive radioactive iodine. After the whole gland is gone, the level should fall close to zero. A level that stays detectable or begins to rise may mean that thyroid tissue or cancer remains or has returned.

Antibodies can change the result. Some people make antibodies against thyroglobulin, called thyroglobulin antibodies (TgAb). One laboratory reports them in 15% to 30% of people with thyroid cancer. These antibodies can make the result read too low or too high. Laboratories usually test for the antibodies at the same time. If the antibodies are present, your doctor may rely on other tests.

A thyroglobulin level is not a diagnosis. Thyroid tissue left behind after surgery can raise it. Benign thyroid conditions can also raise it. Your doctor interprets each result alongside your imaging, treatment history, and earlier results. The tumor markers article explains what blood markers can and cannot show.

What might my report say about thyroglobulin?

Your report may mention thyroglobulin when the pathologist ran an immunohistochemistry stain. A result is a finding, not a diagnosis. The wording usually takes one of these forms:

  • Positive for thyroglobulin. The tumor cells stained. This supports a tumor that started in the thyroid follicular cells.
  • Negative for thyroglobulin. The tumor cells did not stain. The pathologist then relies on other stains and the cell appearance.
  • Thyroglobulin along with other stains. The report often lists several stains together. The combined pattern tells the pathologist where the tumor started.

Questions to ask your doctor

  • Did my pathologist test my tumor for thyroglobulin?
  • What did the thyroglobulin stain show?
  • Does the result confirm that the tumor started in my thyroid?
  • Do I need blood thyroglobulin tests after treatment?
  • How often will you check my level?
  • Do I have thyroglobulin antibodies, and could they affect my results?
  • What level do you expect for me after treatment?
  • What will we do if my level rises?

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