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T3, T4 and TSH: All Important for Thyroid Function

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Hypothyroidism related image Photo: Getty Images

Thyroid hormones regulate metabolism. The U.S. National Library of Medicine's Medline Plus web site tells us that millions of Americans have thyroid disease, causing either too much or too little production of these hormones. Women are affected more often than men.

Hypothyroidism is the condition characterized by too little thyroid activity, with symptoms of weight gain, fatigue, and sensitivity to cold temperatures. Hyperthyroidism is the condition characterized by too much thyroid activity, with symptoms of weight loss, accelerated heart weight, and sensitivity to heat. Hypothyroidism is the more common one.

Dr. Graham R. Williams and Dr. J. H. Duncan Bassett of Imperial College London, UK, provided a review of thyroid hormones. The thyroid produces primarily T4, also called tetraiodothyronine or thyroxine. The name comes from the four iodine atoms in the molecule. T4 is actually a pro-hormone, which is not physiologically active.

Deiodinase enzymes convert T4 to the active hormone T3, also called triiodothyronine, by removing one iodine atom. A similar enzyme inactivates T3 by removing another iodine atom to form T2. The thyroid also produces small amounts of T3.

Hypothyroidism is treated by replacement T4 given orally. However, the deiodinase enzymes may be just as important, according to Williams and Bassett. “Ultimately, an important challenge will be to exploit DIO2 [a deiodinase enzyme] as a drug target to manipulate tissue thyroid status, perhaps in the treatment of metabolic disorders including obesity or skeletal disorders such as osteoporosis and osteoarthritis,” they wrote.

Williams and Bassett explained that the production of T4 is controlled by thyrotropin-releasing hormone (TRH), produced by the hypothalamus, and by thyroid stimulating hormone (TSH), produced by the pituitary gland. TSH is the most commonly measured indication of thyroid function.

When T3 and T4 levels in the blood drop, the pituitary produces more TSH, which is a signal to the thyroid to produce more T4. When T3 and T4 levels rise, the pituitary produces less TSH. This negative feedback loop keeps the metabolic rate in the correct range, for individuals with a healthy thyroid.

The inverse relationship between TSH and T4 makes it possible to measure TSH in a blood test and diagnose thyroid disorders. However, the relationship is more complicated than previously thought, according to Dr. Rudolf Hoermann and colleagues at the Luedensheid Hospital in Germany.

These researchers measured both TSH and T4 in 4,028 adults who had been referred to their hospital for thyroid issues. The data showed deviations from the assumed mathematical form. “A better understanding of the complex nature of the TSH-fT4 relationship may further the development of more precise clinical models and in better defining subclinical states of thyroid dysfunction,” they explained.


1. Medline Plus. Thyroid Diseases. Web. Sept. 15, 2011.

2. Williams GR et al, “Local control of thyroid hormone action: role of type 2 deiodinase”, Journal of Endocrinology 2011; 209: 261. http://www.ncbi.nlm.nih.gov/pubmed/21292729

3. Hoermann R et al, “Complex relationship between free thyroxine and TSH in the regulation of thyroid function”, European Journal of Endocrinology 2010; 162: 1123.

Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.

Reviewed September 19, 2011
by Michele Blacksberg RN
Edited by Jody Smith

Add a Comment1 Comments

Thank you for this article! As someone who has suffered from hypothyroidism since middle school, and suffered ever since, it is nice to hear that there its research going on to better understand the connection between all the didn't readings.

My TSH is currently suppressed, yet my free T4 is still low. My doctors don't know what to do anymore, so hopefully as more research is done on thyroid disorders better treatment options will become available.

September 20, 2011 - 8:44am
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