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High Thyroglobulin Antibodies and Normal TPO Levels

Learn about normal levels, associated conditions, and factors that may cause elevated levels of thyroglobulin antibodies.
High Thyroglobulin Antibodies and Normal TPO Levels
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No single test tells you everything you need to know about your thyroid function. Therefore, several tests run on a blood sample is necessary to get the whole picture of what is happening to this small but mighty organ. And, if you do have a thyroid condition, you must understand what each lab value can tell you about your thyroid. 


Most hypothyroid patients who regularly have thyroid tests will likely recognize TSH and T4. TSH (thyroid-stimulating hormone) comes from the pituitary gland in your brain and tells the thyroid how much thyroid hormone to make. T4 (thyroxine) is the measurement that tells you how much thyroid hormone is circulating in your blood. 


Almost all instances of overt hypothyroidism and subclinical hypothyroidism in the United States are caused by Hashimoto's disease, marked by elevated TPO antibodies. 


TSH and T4 tests alone will likely not give you or your doctor a complete idea of what is going on with your thyroid function. It is also helpful to test T3 (triiodothyronine; the active form of thyroid hormone) and autoimmune markers like thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). 


If your TSH level is above the normal range, it is worthwhile to check your antibodies to determine if Hashimoto's is the cause of your underactive thyroid condition.


What are TPO antibodies?


Thyroperoxidase antibodies (TPO) are present in the blood when there is autoimmune destruction of the thyroid gland. Antibodies are proteins produced by the immune system to protect itself from infections. When a person has an autoimmune thyroid disease, antibodies mistakenly attack one's own thyroid tissues. 


TPO is an enzyme that helps make thyroid hormones. Located in the thyroid gland, TPO helps activate iodide ions that come from food so they can connect tyrosine to make T4 and T3. Suppose an insufficient amount of T4 and T3 are released by the thyroid. In that case, a negative feedback system tells the pituitary gland to release more thyroid-stimulating hormone (TSH) to "stimulate" the thyroid to make more hormones. Subsequently, an increase in TSH increases TPO. 


The presence of thyroid antibodies may mean the immune system is attacking your thyroid. However, a lack of TPO antibodies on a blood test does not always rule out autoimmune disease.


What are Tg antibodies?


Another test used to determine thyroid autoimmunity is TgAb or thyroglobulin antibodies. 


Thyroglobulin (Tg) is a large protein secreted by the thyroid gland that helps produce and store thyroid hormones T4 and T3. Thyroglobulin fluctuates with iodine levels, and elevated levels of Tg may indicate iodine deficiency or excess. 


Iodine is essential for the proper functioning of our thyroid gland, and a deficiency in this nutrient is a risk factor for hypothyroidism (underactive thyroid). Too much iodine can create toxicity symptoms like stomach pain, nausea and vomiting, or neurological dysfunction.


Thyroglobulin is made by follicular cells in the thyroid and generally stays in the thyroid. It is usual for a small amount to enter the bloodstream, but if larger quantities are present outside the thyroid, something is often wrong. The immune system also detects these higher amounts of Tg in the bloodstream and consequently makes Tg antibodies to combat these levels. 


Disorders that cause the thyroid gland to increase, like autoimmune disease, cancer, and nodules, can all cause TgAb levels to rise. 


What do elevated Tg antibodies mean?


TgAb may be elevated for a variety of reasons. Usually, it is due to a thyroid problem, but these antibodies may appear in people with other autoimmune disorders like rheumatoid arthritis, Celiac disease, and type 1 diabetes. 


At least half of all people with Hashimoto's or Graves' disease will have positive TgAb levels. Hashimoto's is an autoimmune thyroid disease where chronic destruction of thyroid cells leads to an underactive thyroid. On the contrary, Graves' disease is where autoimmune processes cause hyperthyroidism (overactive thyroid).


TgAb levels may be present in people with normal thyroid function, and it is most commonly found in women and with age. 


Finally, elevated TgAb levels may also mean a person has growths on their thyroid that may be benign or cancerous. Typically, a thyroglobulin antibodies (TgAb) test is used as a tumor marker test to evaluate the effectiveness of treatment for thyroid cancer. From a clinical perspective, TgAb is less prevalent and less valuable than TPOAb for predicting thyroid dysfunction.

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What if you have high Tg antibodies but normal TPO antibodies?


If your lab results come back with this picture of your thyroid, you may feel stumped. Both TgAb and TPO antibodies are often elevated in conditions like Hashimoto's. However, if TPO antibodies are normal but TgAb levels are high, it may not tell you much about your thyroid. 


TPO antibodies are usually the hallmark sign of autoimmune thyroiditis, and therefore, this is often the preferred test for people trying to rule out this condition. What is more, TgAb does not usually correlate with the degree of thyroid dysfunction, whereas TPO antibodies offer a clearer picture of thyroid health. For this reason, TgAb is not often checked in a complete thyroid function test unless there is suspicion that a tumor is present.


All this to say, if you end up with normal TPO antibodies but elevated TgAB, you will likely need further testing. And your doctor will need to explore other causes within and outside the thyroid.  


A note from Paloma Health


Your thyroid health can be complicated to understand, but testing and monitoring your thyroid hormone levels should not be. 

With Paloma Health's at-home thyroid test kit, you can get a complete picture of your thyroid health to diagnose conditions like hypothyroidism and hyperthyroidism. Should your test results indicate an underactive thyroid, you can follow up with one of our doctors that specialize in hypothyroidism to help you optimize your thyroid hormone replacement treatment.


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Julia Walker, RN, BSN

Clinical Nurse

Julia Walker, RN, BSN, is a clinical nurse specializing in helping patients with thyroid disorders. She holds a Bachelor of Science in Nursing from Regis University in Denver and a Bachelor of Arts in the History of Medicine from the University of Colorado-Boulder. She believes managing chronic illnesses requires a balance of medical interventions and lifestyle adjustments. Her background includes caring for patients in women’s health, critical care, pediatrics, allergy, and immunology.

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