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Thyroid Hormone Testing Explained

Posted by Lena Edwards MD on

Confused about thyroid hormone testing?

…You’re not alone. In fact, most patients AND health care practitioners have difficulty understanding hormones in general and thyroid hormone in particular. One reason for this confusion is that many things can affect the way thyroid hormones work in the body.

 

This can result in a patient having numerous symptoms of thyroid hormone imbalances despite having ‘normal’ blood work. Adding to the challenge of diagnosis is that some thyroid hormone levels can’t be tested in the blood.

 

BUT…one major reason thyroid hormone imbalances go undiagnosed or aren’t properly treated is that thorough testing is often not ordered by most practitioners.

 

This review will discuss:

1. Basic thyroid hormone physiology

2. The different thyroid hormone tests and what they mean 

3. Important yet frequently overlooked factors that can affect thyroid hormone function.

Let’s dive in!

Basic Thyroid Hormone Physiology

 

 

To better understand the types of thyroid hormone tests, it’s important to have a basic understanding of how thyroid hormones are made.

 

Step 1: The hypothalamus (in the brain) produces Thyrotropin Releasing Hormone (TRH).

Step 2: TRH signals the pituitary gland (also in the brain) to produce Thyroid Stimulating Hormone (TSH).

Step 3: TSH signals the thyroid gland to make Thyroxine (T4) and Liothyronine (T3).

 

Here are some important things to know:

 

1. The thyroid gland produces more T4 than T3.

 

2. T4 is relatively inactive and must be converted into T3, the active form of thyroid hormone, in order to exert its effects.

 

3. Thyroid hormones can only circulate in the blood if they are stuck to a protein called Thyroid Binding Globulin (TBG). For thyroid hormones to enter cells and ‘do their thing’, they must detach from this protein. Essentially thyroid hormones must be in their ‘free forms’ in order to work.

 

4. Thyroid hormones indirectly control their own production. This works much like the thermostat in your home. If thyroid hormone levels become too high, the hypothalamus receives the memo from the tissues and turns down the signal for thyroid hormone production. If thyroid hormone levels are too low, this triggers the hypothalamus to ramp up TRH production (and eventually TSH) which leads to increased thyroid hormone production. This is known as a negative feedback loop.

 

5. Nutrient deficiencies, other hormone imbalances, and lifestyle parameters play a huge role in thyroid hormone production and conversion of inactive T4 into active T3.

 

Thyroid Hormone Testing: What & Why

 

The main thyroid hormone tests available are TSH, T4, T3, and reverse T3.Thyroid Peroxidase antibodies, Anti-thyroglobulin antibodies, and TSH Receptor antibodies should also be tested to rule out autoimmune thyroid conditions.

 

TSH: This is the hormone made by the pituitary gland that commands the thyroid gland to produce T4 and T3. It is often the only test health care practitioners will order. If TSH levels are high, something is creating a state of low thyroid hormone production or action (hypothyroidism). If TSH levels are low, it means thyroid hormone levels and/or action is too high.

 

T4 (Thyroxine): T4 is the main thyroid hormone produced by the thyroid gland. It is relatively inactive and must be converted into the more active T3 (in the liver and other tissues). Even though T4 is a very important part of comprehensive thyroid hormone testing, health care practitioners rarely test T4 levels. Make sure to request a free T4 when discussing testing with your health care provider. As discussed above, thyroid hormones only work in their free form. So, when testing this hormone in the blood, the ‘free T4’ needs to be ordered, not the total T4.

 

T3 (Liothyronine): T3 is the more active form of thyroid hormone, most of it coming from its conversion from T4. Again, the free T3 level needs to be ordered. The level of free T3 will provide insight into how much T4 is being converted into T3. If levels of T3 are low, causes of impaired conversion of T3 from T4 should be investigated, including testing for hormone imbalances and nutrient deficiencies.

 

Reverse T3: Reverse T3 is another by-product from T4. T4 can convert into either T3, the active thyroid hormone, or reverse T3 which is “anti-thyroid hormone”. By actively competing with active T3, reverse T3 is one of the safe guards against thyroid hormone overactivity. While having some reverse T3 around is a good thing, too much reverse T3 can cause hypothyroid symptoms, even if other thyroid hormone levels are normal. Examples of things that can raise reverse T3 levels are thyroid hormone medications, stress, and caloric restriction.

Thyroid Antibodies: I test thyroid antibodies in all my patients two main reasons: 1) Autoimmune thyroid disease is among the most common of all autoimmune diseases; 2) Thyroid antibodies can be present long before other thyroid blood tests become abnormal.

The main thyroid antibodies are Thyroid Peroxidase (TPO) and Anti-thyroglobulin (ATGA). ATGA is positive in patients with Hashimoto’s Disease, an autoimmune condition that causes hypothyroidism. TPO levels can be high in both Hashimoto’s Disease and Grave’s Disease. It is important to note that in some cases, antibody level elevation can precede abnormal TSH levels. In patients with symptoms of hyperthyroidism and low TSH levels, testing for TSH Receptor Antibodies (TrAB) can help to determine if Grave’s Disease is present.

It is unfortunate, but our conventional medical training teaches us to check only TSH levels. If the TSH falls within the ‘normal reference range’ , which is quite broad, the testing typically ends there. You can now probably understand why that falls short in determining if and to what extent a patient can have a problem with their thyroid.

Another critical point is to see where in the laboratory reference range blood test results fall. It isn’t enough to simply be ‘in range’. Where the results fall in that range makes a difference and can be an early indicator of a brewing problem. Ideally, the free T3 and Free T4 levels should fall somewhere in the upper 25% of the laboratory reference ranges. Optimal levels of TSH are 0.5 to 2.0 mIU/L. Reverse T3 levels should not exceed 15 ng/dL.

 

Hidden Causes of Hypothyroid Symptoms but Normal TSH

 

Have you ever been convinced your fatigue, weight gain, and depressed mood are coming from a thyroid problem?…then your TSH level comes back ‘in the normal range’!

Here are some of the reasons why this happens:

 

Central Hypothyroidism: This happens when the ‘memo’ from the hypothalamus (the hormone TRH) doesn’t get through to the pituitary. Examples for how this occurs include: 1) The pituitary gland being resistant to TRH (ignores or can’t hear the incoming TRH memo); 2) Prescription medications (i.e. prednisone and other steroids and opioid pain medications); and 3) Tumors of the pituitary or hypothalamus.

 

Other Hormone Imbalances: Every hormone in the human body not only affects but is also affected by every other hormone. The most important and essential hormone for life is Cortisol. Cortisol is the mother of all hormones and is the conductor of the hormonal symphony. If the body is subjected to chronic stress, cortisol will purposely reduce production and negate the action of many other hormones to ensure survival. One of the main hormones that takes a hit as a result of chronic stress is thyroid hormone. 

Female hormone imbalances in estrogen, progesterone, and/or testosterone can also affect thyroid hormone actions, even if thyroid gland function is normal.

 

o Estrogen has numerous effects on thyroid gland and hormone function. It can influence the secretion of TSH from the pituitary gland. Estrogen can also alter the metabolism of thyroid hormones in the liver and other tissues, affecting their availability and activity. The thyroid gland also houses estrogen receptors which allows estrogen to directly influence thyroid cell growth and function.

 

o Progesterone promotes the production and release of thyroid hormones. It regulates the activity of the thyroid gland by modulating certain enzymes involved in thyroid hormone synthesis. Progesterone also has a protective effect on thyroid growth and function. This is a key cause of subclinical hypothyroidism in menopausal women and women with other conditions of progesterone deficiency! Without adequate amounts of progesterone, thyroid hormone production and function will suffer.

 

o Testosterone: Low testosterone levels have been associated with hypothyroidism.

 

**Of note, imbalances in other hormones including Insulin, Growth Hormone, Leptin, and Ghrelin, also impact the production, conversion, and function of thyroid hormones.

Nutrient deficiencies: Several key nutrients are essential for thyroid hormone production and conversion of T4 into T3. Among them are certain amino acids, B vitamins, Iodine, Iron, Selenium, Zinc, Vitamin A, and Vitamin D.

Below is an excellent infographic I borrowed from SpectraCell Labs:

Lifestyle Factors: Numerous lifestyle and environmental factors can also negatively impact thyroid hormone function. These include:

o A diet low in iodine

o Too much iodine intake

o Chronic stress

o Obesity

o Smoking

o Excessive alcohol consumption

o Exposure to environmental toxins

o Certain medications (i.e. steroids, chronic pain medications)

o Poor sleep quality

o Gender (women are more likely to develop subclinical hypothyroidism than men)

o Age (TSH tends to rise as you age, making subclinical hypothyroidism more prevalent in older adults)

 

And there you have it…the whirlwind tour of thyroid hormone testing made as simple as possible. Equipped with this knowledge, you can now approach your health care provider with the right questions and testing requests. Be advised you are more likely to have success in ‘diving deeper’ into potential thyroid (and other hormone) issues if you work with a functional or integrative medicine doctor. Conventional medical practitioners are very set in their ways and often do not feel comprehensive thyroid hormone and other testing is necessary. Be persistent!