In Low T3 Syndrome I, I introduced the Low T3 Syndrome (a.k.a. Euthyroid Sick Syndrome, Non-Thyroidal Illness Syndrome), provided some background on thyroid physiology and metabolism, and emphasized the fact that Low T3 Syndrome is not caused by a problem in the thyroid gland itself.
In this article we’re going to discuss common myths and misconceptions about Low T3 Syndrome and problems diagnosing it in a clinical setting.
This is important because there’s a lot of chatter around the internet these days about this condition. I’m getting a lot of questions about it and I see a lot of people diagnosing themselves with Euthyroid Sick Syndrome on the basis of what I feel is pretty sketchy evidence.
Early Theories on Low T3 Syndrome
The typically accepted view in the scientific literature until quite recently was that the conversion of T4 to T3 is impaired in illness because of a decrease in the activity of D1 & D2 thyroid deoidinases (enzymes responsible for activation of thyroid hormone) in the liver, kidney, skeletal muscles and other peripheral tissues. (1)
The trigger for these changes was thought to be an increase in cortisol and pro-inflammatory cytokines, both of which typically occur in chronic illness.
Recently, however, this theory has been challenged.
This is supported by studies on D1, D2 and D3 knockout mice subjected to treatment with lipopolysaccharide (LPS), an pro-inflammatory endotoxin. These mice, which don’t have any thyroid deiodinase activity, experienced the same decrease in T4 and T3 as wild-type mice. (3)
Also, when wild-type mice are injected with LPS, the fall in T4 and T3 precedes the decline in deiodinase activity (4), and in humans it has been shown that decreased D2 activity doesn’t contribute to Low T3 Syndrome in either prolonged or acute illness. In fact, D2 expression increases two- to three-fold in chronic illness states. (5)
However, evidence now suggests that the fall in T3 found in acute illness is more likely to be caused by impaired production of T3 in the thyroid gland (in turn caused by decreased hypothalamic production of TRH and pituitary production of TSH), and the reduction in thyroid horomone-binding proteins in the serum. (6) We’ll discuss these mechanisms in more detail in the next article.
Problems with Testing and Diagnosis
First, it’s often the case that only total T4 and T3 are tested, rather than free T4 and free T3. While total T4 and T3 give us important information about what the thyroid gland itself is producing, free T4 and T3 tell us how much thyroid hormone is actually available at the cellular level to exert its metabolic effects.
But even when free T4 and T3 are tested, the results are often inaccurate because of the methods used. Although it is often claimed that free T4 is low in patients with Low T3 Syndrome, when the proper methodology is used, free T4 is rarely low—and is often normal or even high. (7)
In fact, is studies using reliable assays for free T4, around 50 percent of patients had low total T4 but only 2 percent had low free T4! (8)
The situation is even more problematic, in some ways, with the measurement of free T3—especially because the free T3 level is fundamental to the diagnosis of Low T3 Syndrome.
It is unequivocal in the literature that total T3 falls during illness, and that the degree of the fall is directly proportional to the severity of the illness. And most routine methods used to measure free T3 commercially and even in research settings tend to show that it drops right along with total T3.
However, results from two studies that have used an improved method for free T3 analysis have found that illness results only in a modest fall in free T3. In fact, free T3 levels were only 10 percent lower in sick patients than in healthy controls. (9)
Another study using this method found that while 70 to 80 percent of sick patients had low total T3, only 27 percent of them had low free T3. (10)
Why does this matter? Two reasons:
- First, a lot of people diagnosed with Low T3 Syndrome may not actually have low free thyroid hormones. This is a concern because some people are supplementing with T4 and/or T3 under the false impression that their hormones are low.
- Second, it implies that the significant changes seen in total T4 and T3 in Low T3 Syndrome are largely due to changes in the serum binding capacity for thyroid hormones.
We’ll discuss each of these points in more detail in the posts to follow.
Articles in this series: