Thyroglobulin

What is a thyroglobulin test?

A thyroglobulin test measures the level of thyroglobulin in a sample of blood. Thyroglobulin is a protein that the thyroid makes. The thyroid is a small, butterfly-shaped gland in the neck. It makes hormones that control many activities in the body, including heart rate and how fast calories from food are burnt.

You may need a thyroglobulin test before starting treatment for thyroid cancer. These test results are compared with the results after treatment. A thyroglobulin test is a type of tumor marker test. Tumor markers are substances made by cancer cells and/or by normal cells in response to cancer in the body. Normally, the thyroid releases small amounts of thyroglobulin into the bloodstream. Cells from common types of thyroid cancer (papillary carcinoma and follicular thyroid cancer) also release thyroglobulin.

The thyroglobulin test may also be needed a few weeks after finishing treatment for thyroid cancer. The test helps show whether any thyroid cells remain in the body. If the treatment is successful, it may still be needed to have the thyroglobulin levels tested from time to time to see if cancer has come back.

Thyroglobulin testing is not used to diagnose thyroid cancer in specific because other thyroid diseases that aren't cancer can also affect thyroglobulin levels. But the test is useful after treatment for common thyroid cancers to see if the treatment worked. If treatment is successful, there should be little or no thyroglobulin in the blood. If thyroglobulin levels remain the same or increase, more cancer treatment may be needed.

What happens during a thyroglobulin test?

A health care professional takes a blood sample from a vein in the arm, using a small needle. After the needle is inserted, a small amount of blood is collected into a test tube or vial.

Preparing for the test:

Usually there is no need for any special preparations for a thyroglobulin test. But taking certain vitamins or supplements should be avoided. 

Other names: Tg, TGB, thyroglobulin tumour marker.

Meaning of the results of a thyroglobulin test

Understanding the results of a thyroglobulin test after treatment can be complicate. The meaning of the results depends on the health history, the type of treatment that was taken, and the results of other tests. 

In general, if one was tested after treatment for thyroid cancer:

- Very low levels or no thyroglobulin may mean that the cancer treatment has worked to get rid of all thyroid tissue, including cancer. But more testing is still needed over time;

- Thyroglobulin levels that stay high or increase may mean that:

            - The treatment did not get rid of all thyroid tissue in the body;

            - There is still thyroid cancer in the body that has grown and may have spread.

- Thyroglobulin levels that were low after treatment but later increased may mean that the thyroid cancer has come back after treatment.

Thyroglobulin - Reference Range

Thyroglobulin testing is primarily used as a tumour marker to evaluate the effectiveness of treatment for differentiated thyroid cancer and to monitor for recurrence.

The normal range for thyroglobulin is:

- 1.40 - 29.2 ng/mL for men

- 1.50 - 38.5 ng/mL for women

In countries where iodine deficiency is common (not in the US), the reference range may be higher.

Women tend to have slightly higher thyroglobulin levels than men.

Pregnant women will typically have high thyroglobulin levels during the third trimester.

Biotin (vitamin B7) should not be taken for 12 hours before giving a blood sample as it may interfere with the results. 

More about the thyroglobulin test

Labs use different methods to measure the amount of thyroglobulin in the blood sample. The test method can affect the results. Hence, it is important to have the tests done the same way, and usually in the same lab. This allows the comparison of the results over time.

A thyroglobulin test may not be useful for monitoring thyroid cancer treatment if there are thyroglobulin antibodies in the blood. These antibodies are proteins that the immune system may make. They attach to thyroglobulin and can make thyroglobulin levels appear lower than they really are.

If having thyroglobulin antibodies, other tests will be used to see if cancer treatment was successful.

Thyroglobulin Testing

Thyroglobulin: Normal Range, High Levels & Thyroid Cancer

Thyroglobulin is a protein that makes thyroid hormones. Checking its levels is important to determine if thyroid cancer has returned after surgery and radiation. Thyroglobulin antibodies may point to autoimmune thyroid diseases such as Hashimoto's and Graves' disease. 

Thyroglobulin is a large protein used by the thyroid gland to make thyroid hormones (T4 and T3) and to store iodine in the body. Thyroglobulin is made in the thyroid by the so-called follicular cells. When the thyroid is stimulated by thyroid-stimulating hormone (TSH), it combines iodine with thyroglobulin to create the hormones T4 and T3.

While most thyroglobulin stays in the thyroid, a small amount leaks out into the bloodstream. Levels in the blood are directly proportional to the size of the thyroid. For example, thyroid cancer cells enlarge the gland and make thyroglobulin in high amounts. In fact, any disorder that increases the size of the thyroid (cancer, autoimmune disease, nodules, etc.) can raise thyroglobulin levels.

Thyroglobulin testing is important to be performed after thyroid cancer surgery, most often in combination with an ultrasound of the neck. This helps to determine if cancer has returned. Detectable thyroglobulin levels that continue to rise a year after surgery suggest that cancer has come back. A neck ultrasound helps in confirming this. 

A thyroglobulin test is mostly used to:

- See if thyroid cancer treatment was successful and guide decisions about more treatment

- Predict how cancer will behave over time 

- See if cancer has returned after successful treatment

Thyroglobulin tests may also be used to help diagnose hyperthyroidism and hypothyroidism, which are common thyroid conditions that aren't cancer.

If levels are undetectable within a year after surgery, the risk of cancer returning is low. If thyroid cancer occurred, however, the thyroglobulin levels will be monitored yearly for lifetime, in order to ensure the patient is still cancer-free.

Thyroglobulin antibodies (TgAb) can interfere with the measurement of thyroglobulin and may cause falsely low or undetectable levels. This is why a TgAb test is always ordered at the same time as a thyroglobulin test.

Antibodies

Antibodies to thyroglobulin (TgAb) are commonly found in people with autoimmune hypothyroidism (Hashimoto's thyroiditis and atrophic thyroiditis) and hyperthyroidism (Graves' disease). More than 50% of people with these diseases test positive for TgAb. However, 2-5% of people with normal thyroid function may also have thyroglobulin antibodies, which tend to increase with age. Women are twice as likely as men to test positive for TgAb.

Antibodies to thyroglobulin are also found in other autoimmune diseases including rheumatoid arthritis (12-23% of patients), type 1 diabetes (30%), and Celiac disease (11-32%). Thyroglobulin antibodies mistakenly tag thyroglobulin as a harmful substance, which causes the body to mount an autoimmune response against it. 

Causes of High Thyroglobulin Levels

Thyroglobulin levels are a marker of thyroid health. Low or high levels don't necessarily indicate a problem if there are no symptoms or if the doctor tells not to worry about it, based on medical history, other analysis etc.

1) Thyroid Cancer

Differentiated Thyroid Cancer 

Differentiated thyroid cancer (DTC) is cancer of the follicular cells of the thyroid. It is the most common cancer of hormone-releasing glands (endocrine) and accounts for 85-95% of all thyroid cancers. DTC produces thyroglobulin, causing its levels in the blood to rise substantially. DTC is treated by surgically removing the thyroid. After surgery, most people are given iodine to destroy any leftover thyroid tissue.

Thyroglobulin testing is very useful after surgery to determine if cancer has returned or spread to other parts of the body. However, it is not a good specific marker for diagnosing DTC, as several other diseases cause high levels. It is also not useful in DTC patients who had normal levels before surgery or in those who still have leftover thyroid tissue after surgery. It is measured 9-12 months after surgery. If the levels are undetectable and an ultrasound of the neck is negative, the patient is cancer-free and has a low risk of the cancer returning. 

If the levels are detectable, then levels will be monitored every 3-6 months to catch trends. If it's decreasing, cancer has probably not returned, while an increasing trend suggests cancer has returned or spread. 

About 20-30% of people with DTC test positive for thyroglobulin antibodies. In these cases, thyroglobulin is not useful in determining if cancer has returned or spread. Instead, doctors will need to rely on other imaging techniques such as a PET or CT scan.

Poorly Differentiated Thyroid Cancer

Thyroglobulin may also be high in poorly differentiated thyroid cancer (PDTC), a less common and more aggressive thyroid cancer form. However, it is not used to monitor the return of cancer in PDTC patients due to its uncertain effectiveness. Initial studies do suggest that detectable thyroglobulin levels after the treatment for this type of cancer increase the risk of cancer returning and death within five years.

2) Benign Thyroid Tumors     

Most benign (non-cancerous) thyroid tumors are capable of producing thyroglobulin. Thyroglobulin levels are usually slightly above normal levels in these cases.

3) Thyroid Nodules    

Nodules are solid areas of tissue or fluid under the skin. They can be caused by either a low or high thyroid activity, but are also at times found in people with normal thyroid function. Most nodules are benign but a small percentage may be cancerous. 

4) Underactive Thyroid    

Most people with an underactive thyroid have high TSH levels, which increase the production of thyroglobulin. People with hypothyroidism may have extremely elevated thyroglobulin levels.

5) Graves' Disease    

Graves' disease is an autoimmune disease that causes an overactive thyroid. Antibodies found in people with Grave's disease activate the TSH receptor, raising thyroglobulin levels.

6) Iodine Deficiency and Excess    

A deficiency in iodine causes the body to release more TSH. In turn, the thyroid produces more thyroglobulin. Taking too much iodine can also raise thyroglobulin levels. Excessive iodine decreases the release of thyroid hormones, which raises TSH and thyroglobulin levels.

7) Liver Cirrhosis    

Cirrhosis is scarring of the liver caused by alcohol, hepatitis, or non-alcoholic fatty liver disease. In a study, those with cirrhosis had much higher thyroglobulin levels than healthy controls.

8) Acromegaly    

Acromegaly is a disorder caused by the overproduction of the growth hormone from the pituitary gland. People with acromegaly have enlarged thyroids that produce higher levels of thyroglobulin.

9) Medications    

The following medications can raise thyroglobulin levels:

- Drugs used to treat an overactive thyroid, such as Methimazole (Tapazole) and Carbimazole (neo-mercazole)

- Amiodarone (Nexterone, Pacerone), an iodine-containing drug used to treat irregular heartbeat. 

High Thyroglobulin Levels

Improving the thyroglobulin levels won't necessarily cause improvement in thyroid function, but it can be used as a biomarker for thyroid health. Approaches to support the thyroid that may also balance high Tg levels are:  

1) Quit Smoking

Smokers have high thyroglobulin levels compared to non-smokers, increase linked to a greater risk of thyroid gland swelling (goiters). Thiocyanate from tobacco smoke prevents the thyroid gland from using iodine properly, which triggers its enlargement. In order to reduce thyroglobulin levels, it is recommended to quit smoking and to avoid tobacco exposure.

2) Iodine

Iodine supplements help lower thyroglobulin levels only if having iodine-deficiency. The iodine dosage will vary depending on the severity of the deficiency. At mild iodine deficiency, taking 80 μg/day of iodine reduces thyroglobulin levels by 24%. However, iodine supplementation may not be recommended if iodine levels are normal.

3) Selenium

In a study of people with hypothyroidism, 20-60 mg/day of selenium decreased thyroglobulin levels.

4) Vitamin A

Vitamin A helps lower thyroglobulin levels if vitamin A-deficient. In vitamin A-deficient people, taking vitamin A decreased thyroglobulin levels.

Low Thyroglobulin Levels

Thyroglobulin levels are a marker of thyroid health. Low or high levels don't necessarily indicate a problem if there are no symptoms or if the doctor tells not to worry about it, due to medical history and other analysis.

1) Too Much Synthetic T4 hormones

Thyrotoxicosis factitia (TF) is a condition caused by taking too much synthetic T4 hormones (levothyroxine). It mimics an extremely overactive thyroid. Thyroglobulin levels are very low or undetectable in people with this condition. Thyroglobulin can help doctors determine if an overactive thyroid is due to TF or other causes.

2) Thyroid Removal

Thyroglobulin is only made in the thyroid or by thyroid cancer cells. This means that people without a thyroid will have undetectable levels of thyroglobulin (in the absence of thyroid cancer).

3) Medications

The following drugs can lower thyroglobulin levels: 

- Levothyroxine (Synthroid)

- Octreotide (Sandostatin), a synthetic somatostatin hormone

- Salicylate (Aspirin)

- Prednisolone (Omnipred), an anti-inflammatory corticosteroid

Low Thyroglobulin Levels and ways to support the thyroid

Improving thyroglobulin levels doesn't necessarily cause improvement in thyroid function, but it can be used as a biomarker for thyroid health.

The following support the thyroid and may also balance low Tg levels. 

1) Cold Exposure 

Cold exposure activates brown adipose tissue (BAT), a type of fat tissue that generates heat and keeps the body warm. Thyroid hormones are required to activate brown fat tissue. Essentially, cold temperatures increase the activity of the thyroid gland to keep the body warm, which makes more thyroglobulin as a result. 

A study found that hunters exposed to cold weather on a daily basis had higher thyroglobulin levels than city-dwellers.

In a study of people living in Antarctica, thyroglobulin levels increased after seven months (due to an increase in TSH levels).

2) Limit Saturated Fats

Rats fed a diet high in saturated fats had decreased thyroglobulin levels and an underactive thyroid gland as a result of damage and swelling. If struggling with underactive thyroid, it is recommended limiting the intake of saturated fats.

However, this may only be available for animals and human clinical trials are needed to come to definitive conclusions.

Genetics

There are at least 52 mutations in the thyroglobulin gene that correlate with low thyroglobulin levels or irregularly-shaped thyroglobulin. Many of the mutations result in inherited (congenital) hypothyroidism, which causes an underactive thyroid in newborns.

Conclusions

Thyroglobulin is important to monitor if you had thyroid cancer and underwent surgery in the past. The test will help determine if cancer has a high or low chance of coming back; lower levels indicate a better outcome. 

Thyroglobulin marker increases proportionally to the size of the thyroid gland, which means that benign tumors, nodules, and Grave's disease can also raise its blood levels.

Some complementary approaches that may support the thyroid, as measured by lower thyroglobulin, include quitting smoking, selenium supplements, and iodine for deficient people. Cold exposure may support the underactive thyroid and increases Tg levels.