Understanding thyroid health can be tricky. Medical professionals have long been taught that the only thyroid test that matters is the TSH. Although TSH is vital for understanding thyroid health, having a clear picture of the downstream hormonal cascade provides valuable insight into the health and wellbeing of an individual.
Although data is limited, it is estimated that screening with TSH alone misses roughly 7% of individuals with overt thyroid dysfunction (1). Functional medicine practitioners typically start assessing thyroid health by ordering TSH, Free T4, Free T3, and Reverse T3. These tests assess hormone levels in the blood and can be obtained via a blood draw or blood spot analysis.
TSH (thyroid-stimulating hormone) is the hormonal signal sent from the pituitary gland to the thyroid to tell the thyroid how much hormone to synthesize and release. TSH is part of a sensitive hormonal feedback loop and is the most common thyroid test ordered by physicians (1). TSH functions like a thermostat and can give you a general sense of whether or not the body thinks there is too much, not enough or just the right amount of thyroid hormone floating around.
TSH also functions as an early warning system and is often abnormal before other thyroid tests fall out of range (2). When TSH is elevated, the body is signaling that an increase in the production and release of thyroid hormone is necessary. If TSH is very low, the body is scaling back on any further production because there is adequate or excess thyroid hormone in the periphery.
Active vs Inactive Thyroid Hormone
Once the thyroid gets the TSH production memo, it produces a blend of active and inactive thyroid hormone. Of the thyroid hormone that is made and released at the level of the thyroid, 90% is inactive hormone, T4, and 10% is the active hormone T3 ( 3). The T4 hormone makes its way around the body, where it is then converted to either the bioactive T3 or the less active Reverse T3 (rT3) in the cells of the liver, kidney, brain and skeletal muscle.
T3 is the power horse of the thyroid hormones and is responsible for entering the nucleus of the cells and executing the thyroid hormone’s downstream effects. T3 thyroid hormone has profound physiological effects in the body and affects everything from our blood vessels to our bones. Without adequate function of T3, we see the hallmark symptoms of fatigue, hair loss, constipation, and weight gain.
Shutting Down Production of T3
With great power comes fine tuned control and the body has numerous ways of shutting down the production of T3 in response to stress or other physiologic changes. The main way to rapidly decrease production of T3, is to flip the conversion from T4 from T3 to its largely inactive counterpart, Revere T3 (rT3). Reverse T3 (rT3) looks structurally similar to T3 but with different placement of the iodine atoms preventing it from exerting the usual binding functions of T3 (2).
Although long thought to be completely biologically inactive, there is growing evidence that the rT3 does exert some of its own biological effects on the brain and may also competitively inhibit T3 from binding to its target receptor sites (4), (5).
T4 and T3 Conversion Process
The T4 to T3 conversion process is highly regulated and sensitive to environmental factors and nutrient availability. Physiologic and emotional stress, chronic infections, and nutrient deficiencies all increase the amount of T4 that gets converted to rT3 (6). Diets that have adequate zinc and selenium as well as certain herbs such as Ashwagandha, can increase the conversion of T4 to the bioactive T3 (7), (8), (9).
By collecting values for TSH, Free T4, Free T3 and Reverse T3 you get a full picture of this complex physiologic process. If you are searching for a root cause of thyroid dysfunction, you can quickly get a sense of whether problems are arising in the production of thyroid hormone, the conversion of thyroid hormone or a combination of both.
What reference ranges should you target?
- TSH: The ideal TSH can vary widely based upon a person’s age, gender and stage of life. The typical reference range provided by most labs is around 0.45-4.12 mlU/L. There is growing consensus that a narrower TSH range of 0.5 to 2.5 mlU/L may be more appropriate for most healthy adults (10). The National Academy of Clinical Biochemistry released data indicated that more than 95% of normal individuals have a TSH level below 2.5 mlU/L (10). Many Functional Medicine practitioners target an optimal TSH of 0.5-2.5 in most of their adult clients.
- T4: The normal reference range in most labs is around 0.93-1.70 mlU/L and most practitioners aim to stay within this range.
- T3: The normal reference range in most labs is around 2.8-4.0 mlU/L and most practitioners aim to stay within this range.
- Reverse T3: Normal reference range of rT3 is 8-25 ng/dl. There is no broad consensus on optimal rT3, but many functional medicine practitioners target less than 15 or less than 12 in their clients.
Any other lab tests to check?
Depending on the clinical scenario, you may want to consider checking thyroid antibodies and a couple of key nutrient levels.
- Thyroid Peroxidase Antibodies are antibodies against a key enzyme involved in the production of thyroid hormone and is often associated with the autoimmune condition Hashimoto’s Thyroiditis
- Thyroglobulin Antibodies are antibodies against stored form of thyroid hormone and when elevated can lead to an underproduction of thyroid hormone
- The production of thyroid hormones and the conversion of T4 to T3 by the iodothyronine deiodinase enzymes require specific nutrient cofactors: Selenium, Zinc, Iodine and B2, B6, B3 are all associated with the production and activity of thyroid hormones. Deficiencies in any of these nutrients can be a contributing factor in thyroid dysfunction.
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