Thyroid Cascade Profile Test

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Thyroid blood tests are the primary diagnostic tool used to assess thyroid function and receive a diagnosis of thyroid disease. Fortunately, blood tests provide a good picture of what is happening inside the thyroid and can sometimes even offer cues into what is happening with the pituitary-thyroid axis. What is more, when the proper tests are ordered, we can even determine if the thyroid dysfunction is due to an autoimmune disease (autoimmune thyroiditis) or not. The thyroid cascade profile test is a diagnostic tool that helps providers understand thyroid health in their patients. Here, we dive into how the test works and what each test can tell you about your thyroid.

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Your doctor may order a thyroid cascade profile test to determine if you are suffering from a condition such as hyperthyroidism or hypothyroidism. The test first starts by looking at thyrotropin (TSH, or thyroid-stimulating hormone). If the TSH level is not within normal limits, the lab immediately tests free thyroxine (FT4). If FT4 is normal and TSH is below normal limits, triiodothyronine (T3) is assessed. Lastly, if TSH levels are significantly elevated above normal limits, thyroperoxidase antibodies (TPO antibodies) will be tested for autoimmune disease.

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Knowing what each marker means can be complicated, so we have broken it down for you below.

Thyrotropin (TSH)

TSH is a hormone secreted by the pituitary gland to tell the thyroid gland how much thyroid hormone it should make and secrete. The pituitary gland is an endocrine gland that rests just below the hypothalamus in the brain. Technically, the hypothalamus oversees all hormone production. However, the pituitary gland is technically the master gland of all other endocrine glands of the body, as it releases hormones that tell each endocrine gland what to do.

The pituitary gland uses TSH to tell the thyroid how much hormone to secrete based on feedback from other tissues in the body. If the pituitary gland does not detect high enough levels of FT4, it will release more TSH to "stimulate" thyroid hormone production. Likewise, if high levels are detected, it will lower TSH levels to help turn off or minimize thyroid hormone production.

TSH can tell if you have hyperthyroidism or hypothyroidism. However, it cannot tell what is causing it, so additional testing may be performed.

Thyroxine (T4)

Thyroxine is a form of thyroid hormone. Two forms of T4 exist in our bodies: free T4 and bound T4. Free T4 (FT4) is the active form of thyroxine found in the bloodstream, and when converted to T3, it enters your cells when required. Bound T4 "binds" to specific proteins that prevent it from entering your tissues. Measuring FT4 is the most beneficial assessment form, as it can tell how much thyroxine the thyroid releases. The thyroid cascade profile test only assesses FT4, not total T4, which is generally a less specific and less accurate in understanding what is happening.

When FT4 is low, the thyroid is underactive; therefore, you may have hypothyroidism. Likewise, if FT4 is high, it may mean the thyroid is overactive, and you may have hyperthyroidism.

Triiodothyronine (T3)

T4 and T3 are known collectively as thyroid hormones, as T4 is converted into T3. Like T4, T3 is also a thyroid hormone that can be free or bound. However, unlike T4, T3 is the form of the hormone that is usable by cells. When T4 passes through certain organs, such as the liver, it converts into T3, which can then enter cells. About 20% of the thyroid hormone in your body is T3, whereas 80% is T4.

Testing T3 is most often used to diagnose hyperthyroidism. T3 is assessed when FT4 is normal, but TSH is low in a thyroid cascade profile test. Again, when TSH is low, it can mean a person has hyperthyroidism.

Thyroperoxidase antibodies

Thyroperoxidase antibodies may indicate the presence of Hashimoto's thyroiditis or Graves' disease. Both are autoimmune conditions, meaning the body's immune system attacks the thyroid gland. Hashimoto's is the leading cause of hypothyroidism in the United States, and Graves' is a very common cause of hyperthyroidism.

Antibodies are proteins the immune system makes to fight foreign invaders like bacteria and viruses. When autoimmunity occurs, the immune system produces antibodies to fight itself, which can be highly detrimental to our health when left untreated. Sometimes, antibodies directly attack tissue, whereas others force the thyroid to make excess amounts of thyroid hormone.

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Lab values and ranges vary between labs. Therefore, looking at the set parameters for your specific lab performing the panel is necessary. Generally speaking, and followed by the Mayo Clinic, the following are parameters for when the cascade is initiated:

• If TSH is <0.3 mIU/L, then FT4 is tested (to assess for hyperthyroidism)
• If FT4 is normal and TSH is <0.1 mIU/L, then T3 is tested (to evaluate for hyperthyroidism)
• If TSH is >4.2 mIU/L, then FT4 and thyroid antibodies are tested (to evaluate for hypothyroidism and Hashimoto's)

Your provider should review your results with you and help you understand what they mean about your thyroid function. If you are diagnosed with hypothyroidism, you will likely need to be on thyroid hormone replacement medication for the rest of your life. Hypothyroidism can be well managed with the correct dose of thyroid medication after taking a full-panel, at-home thyroid test kit. If you have hyperthyroidism, you may need to take antithyroid medications, and if problems persist, you may need to have some of your thyroid gland removed to reduce hormone secretion.

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