What are the other Names for this Test? (Equivalent Terms)

• Serum Thyroglobulin Test
• Tg Testing
• Thyroglobulin (Tg) & Thyroglobulin Antibody (TgAb) Testing

What is Thyroglobulin (Tg) Testing? (Background Information)

• Thyroglobulin (Tg) is a glycosylated protein, produced by the follicles of the thyroid gland. It is produced only in the thyroid tissues of the body. A test of thyroglobulin is thus helpful in understanding thyroid conditions
• Thyroglobulin Testing may be performed as a stand-alone test, or as a part of a panel of thyroid tests
• It is usually performed along with a test for anti-thyroglobulin antibodies. These are called thyroid autoantibodies (TgAb) and/or, thyroid peroxidase antibodies (TPOAb)

The most common method for detecting thyroglobulin levels is enzyme-linked immunosorbent assay (ELISA). Other methods commonly adopted for thyroid testing, include the following:

• Enzyme-multiplied immunoassay technique (EMIT)
• Microparticle capture enzyme immunoassay (MEIA)
• Clone enzyme donor immunoassay (CEDIA)
• Fluorescence polarization immunoassay (FPIA)
• Radioimmunoassay (RIA)
• Immunoradiometric assay (IRMA)
• Immunochemiluminometric assay (ICMA)

What are the Clinical Indications for performing the Thyroglobulin (Tg) Testing?

Thyroglobulin (Tg) Testing is primarily used as a tumor marker. Since, some tumors, such as papillary carcinoma and follicular carcinoma of the thyroid, produce thyroglobulin; it is considered to be a tumor marker.

• In such cases, a baseline level of thyroglobulin is determined, prior to cancer treatment modalities, like total thyroidectomy or radioiodine thyroid ablation. Thyroglobulin levels are helpful in evaluating the effectiveness of thyroid cancer treatment
• It is also very important to monitor for any recurrence of thyroid cancer. With some thyroid cancer cases, the levels of thyroglobulin increases, when the tumor recurs. Hence, the healthcare provider will periodically perform Tg Blood Test

Serial thyroglobulin level measurements are recommended, since these are more helpful than a single measurement. It is ideal to perform serial measurements at the same laboratory, because different laboratories may use different methodologies, in order to measure thyroglobulin levels.

• Initially, the serial thyroglobulin levels may be measured, a few weeks to a few months, after cancer treatment
• After the initial serial monitoring, cancer monitoring for recurrence, may be performed with yearly thyroglobulin measurements
• After surgery for thyroid cancer, Tg measurement is determined. Since, the thyroid gland is removed, the patient may be required to take daily dose of thyroxine medication; Tg levels are performed in such patients

Thyroglobulin is not a diagnostic marker for thyroid cancer. This means that in an individual, who has increased levels of thyroglobulin, it does not mean that they have cancer.

• The Tg test is also helpful in the workup of individuals, who are showing signs and symptoms of either hyperthyroidism or hypothyroidism
• Thyroglobulin test is not a screening test for asymptomatic patients, as part of a well-being checkup. This means, Tg tests cannot be used in the general population to determine, if an individual has thyroid cancer or not
• In individuals with increased levels of thyroglobulin, it does not indicate any malignancy. Increased levels of thyroglobulin can be seen in many non-malignant thyroid conditions. In other words, it is not specific for thyroid cancer and Tg can be temporarily elevated with many thyroid conditions
• Thyroglobulin levels are measured post-surgery, to determine whether the tumor is completely removed (complete resection of tumor). In such cases, if thyroglobulin levels are not detected; then, it means that the surgery is successful and no tumor was left behind
• Occasionally, small amount of thyroid tissue may be inadvertently left behind by the surgeon, which may cause thyroglobulin to be present in low quantities. This is the reason why surgeons may recommend radioactive iodine therapy after the surgery, to destroy the small residual thyroid tissue. After the radioactive ablation therapy, the thyroglobulin protein should be absent in blood

How is the Specimen Collected for Thyroglobulin (Tg) Testing?

Sample required: Blood

Process: Insertion of needle into a vein (arm).

Preparation required: None

What is the Significance of the Thyroglobulin (Tg) Testing Result?

Increased levels of thyroglobulin levels are seen with:

• Certain types of thyroid cancers, such as papillary and follicular cancers, including metastatic papillary and follicular cancers
• Not all thyroid cancer (even papillary and follicular) cause increased levels of Tg. Occasionally, benign tumors of thyroid, such as benign follicular adenoma, can result in increased Tg levels
• Recurrent thyroid cancer, if the original tumor produced thyroglobulin. Rising Tg levels in patients, who have undergone total thyroidectomy surgery, is a cause of concern and may indicate cancer recurrence

Newborns have high thyroglobulin levels. Usually, the levels slowly decrease, and by age 2 years the levels are in adult range.

Decreased thyroglobulin levels are seen with:

• Cases of fictitious thyrotoxicosis
• Infantile goiter, resulting in hypothyroidism

There are many factors that may interfere with the measurements of Thyroglobulin.

• Decreased Tg level values are seen due to the presence of autoantibodies to thyroglobulin protein, which are called:
  • Thyroid autoantibodies (Tgab and or thyroid peroxidase antibodies-TPOAb )
  • Anti-thyroid antibodies
  • Antimicrosomal antibodies
  • Thyroid microsomal antibodies
  • Thyroperoxidase antibodies
  • Antithyroperoxidase
  • Antithyroglobulin antibodies
  • Thyroglobulin antibodies
  • Thyroid-stimulating immunoglobulin

Presence of such autoantibodies occurs in normal individuals (approximately 1 in 10 individuals, have such antibodies).

• Such autoantibodies are found in one-quarter of the patients with papillary carcinoma of thyroid
• Anti-thyroglobulin antibodies are present in individuals with Hashimoto's thyroiditis and Graves' disease. Presence of the type of anti-thyroglobulin specific antibodies, aids in the diagnosis of these conditions
• It is important to note that even normal individual without any thyroid issues, may have anti-thyroglobulin antibodies

Thyroid-stimulating hormone (TSH) & Thyroglobulin (Tg):

• Thyroid-stimulating hormone is a hormone that is made by the thyrotrope cells in the anterior pituitary gland
• The purpose of TSH is to stimulate the thyroid gland to make thyroxine (T4), which is then converted to triiodothyronine (T3) in the liver and thyroid gland. During the process, thyroglobulin is released in blood as a by-product, during hormone production
• It has been postulated that TSH helps the thyroid cancers grow. If TSH levels are lowered, then it can help in slowing down the tumor growth
• Thyroxine medicine (such as synthroid, levoxyl, unithroid) helps keep the TSH levels low by having a negative effect on TSH production; in the anterior pituitary gland (this is called negative feedback)
• High levels of TSH can cause a 10-fold increase in Tg levels. Hence, It is important not to compare thyroglobulin levels, measured while taking thyroxine medicine (when TSH is low) with the thyroglobulin level measured when TSH is high
• This is the reason why thyroglobulin levels are usually performed with other tests, such as anti-thyroglobulin antibodies and thyroid-stimulating hormone levels

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

• A pre-operative thyroglobulin level is not performed before diagnostic fine-needle aspiration cytology (FNAC)

After surgery, Tg measurement is performed, while the patient is taking their daily dose of thyroxine medication (TSH will be low, in such cases). In the past, the physicians asked patient’s to stop taking thyroxine, 2-3 weeks before testing for thyroglobulin level. The reason for this was to stimulate the anterior pituitary to make more TSH, which in turn caused the residual cancer, if any present, to produce thyroglobulin. This stoppage of thyroxine is not done now, for 2 reasons.

• Firstly, the patient has uncomfortable symptoms of hypothyroidism, when thyroxine is stopped
• And secondly, a recombinant TSH-protein is now available to stimulate the production of Tg without the need to stop thyroxine
• It is important to note that an increased thyroglobulin level, resulting from a cancer, does not indicate that the cancer is more aggressive

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.