It’s not uncommon for a person to experience hypothyroid symptoms and be told by their doctor that all their lab tests are “normal” and that it can’t be a thyroid problem. It’s frustrating for both the physician and the patient, who just wants to feel better. So what is the solution? It may simply be a matter of understanding deiodinases and looking for treatments to help them work better.
What’s a deiodinase?
Deiodinase is a category of enzymes which support conversion of inactive T4 thyroid hormone to the active form T3 in the body. The enzyme activates the hormone by removing iodine molecules from it. Ultimately, deiodinases control the amount of inactive and active thyroid hormone in the tissues of the body.
While the discussion of deiodinases may seem at first to be an irrelevant technical detail, scientists are beginning to see that deiodinase activity is actually at the very heart of healthy thyroid hormone functioning. Just a small glitch in deiodinase activity can cause complete confusion about thyroid status. A person could be experiencing hypothyroid symptoms, yet their TSH and T4 may look totally normal on lab tests.
The active thyroid hormone T3 has its action inside the nucleus of every cell that has a nucleus. Most of the T3 that makes it into the nucleus is generated inside the cell itself through the action of a deiodinase called D2. It’s easy to see why thyroid blood tests don’t accurately measure the T3 that’s active in the nucleus because they can’t measure how much T3 is generated inside the target tissue cells. D3 is a deiodinase that generates the inactive reverse T3 (RT3) from T4. Both D2 and D3 are under cellular regulation. The T3 that’s delivered to the cells by the blood is only part of the story. The majority of the story is determined by whether signals are causing the cell to turn up T3 production by D2 or to turn down T3 production by D3 making RT3 instead. All deiodinases rely on selenium for their activities and when selenium is deficient, it can cause a reduction in active thyroid hormone.
The biggest problem is that common and prevalent life situations can lead to a downregulation of D1 and hinder conversion of T4 to T3 throughout the body, where it is needed to regulate metabolism. Life situations which downregulate D2 include stress, depression, dieting, excess weight, insulin, chronic fatigue, fibromyalgia, and environmental toxin exposures- things we all experience at some time in our lives. Extreme D2 downregulation can cause a person to experience hypothyroid symptoms (fatigue, weight gain, etc), despite the presence of adequate T4 thyroid hormone levels (Wilson’s Temperature Syndrome). This isn’t truly hypothyroidism, but it is a problem of poor T4- T3 conversion. Unfortunately, thyroid hormone blood tests only measure thyroid hormone levels, not deiodinase activity. Blood tests may indicate a person may have plenty of T4, but if it’s not being converted properly, they still feel terrible. Giving that person more T4, in the form of Synthroid, won’t always help them feel better and may even cause them to feel worse.
Understanding how deiodinases work is essential to getting a proper thyroid diagnosis and getting to the root cause of the problem. Considering how common it is to experience stress or any of the other factors which downregulate D2 thyroid conversion, it’s not surprising that hypothyroid symptoms are widely prevalent and puzzling to many doctors. This is when understanding Wilson’s Temperature Syndrome can be extremely helpful. Read more about Wilson’s Temperature Syndrome HERE.
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Maia AL, Kim BW, et al. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. Journal of Clinical Investigation, 2005 September.
De Groot Leslie J. Non-Thyrodial illness syndrome is a manifestation of hypothalamic-pituitary dysfunction,and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22:57–86.