Thyroglobulin is a protein used to make thyroid hormones. Doctors mainly check its levels to determine if thyroid cancer has returned after surgery and radiation. Thyroglobulin antibodies, on the other hand, point to autoimmune thyroid diseases such as Hashimoto’s thyroiditis. Read on to learn more about thyroglobulin and what causes abnormal levels.

What Is Thyroglobulin?

Thyroglobulin is a large protein used by the thyroid gland to make thyroid hormones (T4 and T3) and store iodine in the body [1].

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 (the “4” and “3” refer to the number of iodine atoms attached) [2].

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 [2].

Thyroglobulin Test – When is it Ordered?

Doctors usually order the thyroglobulin test after thyroid cancer surgery, most often in combination with an ultrasound of the neck. It helps 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 [3, 2].

If levels are undetectable within a year after surgery, the risk of cancer returning is low. If you had thyroid cancer, however, your levels will be monitored yearly for life to ensure you’re still cancer-free [2].

Thyroglobulin antibodies (TgAb) can interfere with the measurement of thyroglobulin and cause falsely low or undetectable levels. This is why a TgAb test is always ordered at the same time as a thyroglobulin test [4].

Normal Thyroglobulin Levels

The normal range for thyroglobulin is:

  • 1.40 – 29.2 ng/mL (μg/L) for men
  • 1.50 – 38.5 ng/mL for women

In countries where iodine deficiency is common (not the US), the reference range may be higher [5, 6, 7].

Women tend to have slightly higher thyroglobulin levels than men [8].

Pregnant women will typically have high thyroglobulin levels during the third trimester [9].

You shouldn’t take biotin (vitamin B7) for 12 hours before giving a blood sample as it may interfere with the results [10].

Thyroglobulin 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 [11, 12].

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 [11, 12, 13].

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%) [11].

Thyroglobulin antibodies mistakenly tag thyroglobulin as a harmful substance, which causes the body to mount an autoimmune response against it [14].

Causes of High Thyroglobulin Levels

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 [15, 16].

DTC is treated by surgically removing the thyroid. After surgery, most people are given radioactive iodine to destroy any leftover thyroid tissue [16].

Thyroglobulin 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 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 [2, 17, 18].

Thyroglobulin is measured 9 – 12 months after surgery. If thyroglobulin 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  [16, 17, 3].

If thyroglobulin 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 [17, 3].

Cancer returns in about 5 – 20% of the cases and spreads to other parts of the body in 0 – 15% [3].

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 [3].

Poorly Differentiated Thyroid Cancer

Thyroglobulin may also be high in poorly differentiated thyroid cancer (PDTC), a less common and more aggressive thyroid cancer form [2].

However, thyroglobulin is not used to monitor the return of cancer in PDTC patients as its effectiveness has not been confirmed. 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 [19, 20].

2) Benign Thyroid Tumors

Most benign (non-cancerous) thyroid tumors are capable of producing thyroglobulin. Thyroglobulin levels are usually only slightly above normal levels in these cases [21].

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, but are also at times found in people with normal thyroid function. Most nodules are benign but a small percentage may be cancerous [22].

One study found that 58 out of 61 people with thyroid nodules had high thyroglobulin levels. The average thyroglobulin level was 205.4 ng/mL [23].

4) Underactive Thyroid

Most people with an underactive thyroid have high TSH levels, which increase the production of thyroglobulin. In a study of 18 people with hypothyroidism, 12 had extremely elevated thyroglobulin levels [24, 25].

4) 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 [26, 3].

5) Iodine Deficiency and Excess

A deficiency in iodine causes the body to release more TSH. In turn, the thyroid produces more thyroglobulin [27].

Taking too much iodine can also raise thyroglobulin levels. Excessive iodine decreases the release of thyroid hormones, which raises TSH and thyroglobulin levels [28].

6) Liver Cirrhosis

Cirrhosis is scarring of the liver caused by alcohol, hepatitis, or non-alcoholic fatty liver disease. In a study of 134 people, those with cirrhosis had 84% higher thyroglobulin levels than healthy controls [29].

7) 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 [30].

8) Medications

The following medications can raise thyroglobulin levels:

  • Drugs used to treat an overactive thyroid, such as Methimazole (Tapazole) and Carbimazole (Neo-mercazole) [31, 32]
  • Amiodarone (Nexterone, Pacerone), an iodine-containing drug used to treat irregular heartbeat [33]

How to Decrease Thyroglobulin Levels

1) Fasting

A four-day fast reduced thyroglobulin levels by 60% in a study of seven people [34].

2) Selenium

In a study of 18 people with hypothyroidism, 20 – 60 mg/day of selenium decreased thyroglobulin levels [35].

3) Iodine

Iodine supplements will help lower your thyroglobulin levels only if you’re iodine-deficient. The iodine dosage will vary depending on the severity of the deficiency.

A study of 100 people with mild iodine deficiency found that taking 80 μg/day of iodine reduced thyroglobulin levels by 24% [36].

Another trial of 112 iodine-deficient people found that supplementing with 150 μg/day of iodine decreased thyroglobulin by 27% after 24 weeks. A higher dose of iodine (200 μg/day) for six months reduced thyroglobulin by 32% in 163 iodine-deficient people [37, [38].

4) Vitamin A

Vitamin A will help lower your thyroglobulin levels only if you’re vitamin A-deficient.

In 404 people with vitamin A-deficiency, supplementing with 400,000 IU vitamin A over six months reduced thyroglobulin levels by 25%. In another trial of 138 vitamin A-deficient people, taking 400,00 IU vitamin A over 10 months decreased thyroglobulin levels [39, 40].

5) Resveratrol

Resveratrol, the antioxidant found in red wine, decreased thyroglobulin levels in the thyroids of rats [41].

6) Quercetin

The antioxidant flavonoid Quercetin decreased the production of thyroglobulin in rat thyroid cells [42].

7) Quit Smoking

In a study of over 400 people, 47% of smokers had high thyroglobulin levels compared to only 18% of non-smokers. This increase was linked to a greater risk of thyroid gland swelling (goiters). A compound in tobacco smoke called thiocyanate prevents the thyroid gland from using iodine properly, which triggers thyroid gland enlargement [43, 44].

If you’re looking to reduce your thyroglobulin levels, quit smoking and/or avoid tobacco exposure.

According to a large observational study of 10k people, the link between smoking and higher thyroglobulin levels is evident. In a study of 140 people, the average thyroglobulin levels of smokers were 40 ng/mL whereas the average levels in non-smokers were 24.4 ng/mL. [45, 8].

Causes of Low Thyroglobulin Levels

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 [46].

Thyroglobulin can help doctors determine if an overactive thyroid is due to TF or other causes [47].

2) Having Your Thyroid Removed

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) [47].

3) Medications

The following drugs can lower thyroglobulin levels:

  • Levothyroxine (Synthroid) [48]
  • Synthetic TSH (Thyrogen) [49]
  • Octreotide (Sandostatin), a synthetic somatostatin hormone [50]
  • Salicylate (Aspirin) [51]
  • Prednisolone (Omnipred), an anti-inflammatory corticosteroid [51]

Factors that Increase Thyroglobulin Levels

Thyroglobulin levels will increase along with TSH as the thyroid becomes more active. If you have an underactive thyroid, the following may be beneficial for you.

1) Cold Exposure

Cold exposure activates brown adipose tissue (BAT), a type of fat tissue that generates heat and keeps you 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 [52].

A study of 535 people living in Greenland found that hunters exposed to cold weather on a daily basis had 46% higher thyroglobulin levels than city-dwellers [52].

In a study of 12 people living in Antarctica, thyroglobulin levels increased by 24% after seven months (due to a 43% increase in TSH levels) [53].

2) Forskolin

Forskolin increased the production of thyroglobulin in thyroid cell-based studies. It worked by increasing the activity of genes that code for thyroglobulin (TG) [54, 54].

3) Avoid 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 you’re looking to support your thyroid and general wellness, avoiding saturated fats is a must [55].

Genetics of Thyroglobulin

There are at least 52 mutations in the thyroglobulin gene that result in low thyroglobulin levels or irregularly-shaped thyroglobulin. Many of the mutations result in inherited (congenital) hypothyroidism, which causes an underactive thyroid in newborns [56, 57].

SNPs in the thyroglobulin gene that are associated with a higher risk of Graves’ disease include [58]:

  • rs2256366
  • rs2687836
  • rs3739266
  • rs2253035

SNPs in the thyroglobulin gene that are associated with a higher risk of Hashimoto’s disease include [59, 60, 58]:

Irregular Thyroglobulin Levels?

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Takeaway

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

This marker increases proportionally to the size of the thyroid gland, which means that benign tumors, nodules, an underactive thyroid, and Grave’s disease can also raise its blood levels. Some natural interventions that may reduce your thyroglobulin include fasting, quitting smoking, selenium supplements, and plant antioxidants like resveratrol and quercetin.

About the Author

Will Hunter

BA (Psychology)
Will received his BA in Psychology from the University of California, Los Angeles. 
Will's main passion is learning how to optimize physical and mental performance through diet, supplement, and lifestyle interventions. He focuses on systems thinking to leverage technology and information and help you get the most out of your body and brain.

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