Are conventional thyroid function tests as reliable as we’re led to believe?

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This morning, I saw this piece of news on the BBC website which reports on the accusation some doctors (endocrinologists) have leveled that some doctors are misdiagnosing and mistreating thyroid disease. The main gripe appears to be the fact that some doctors are willing to entertain the diagnosis of low thyroid function (hypothyroidism), even when blood tests are normal. Moreover, thyroid hormone can be initiated in these patients, which may be harmful.

Key to understanding why some doctors do not put their full and utter faith in conventional blood tests when assessing thyroid function is a knowledge of the normal physiology of the thyroid. The thyroid is responsible for producing thyroid hormones which stimulate the metabolism and facilitate energy production in the body’s cells. The two main thyroid hormones are T4 and T3. A lack of thyroid hormone can lead to symptoms such as fatigue and lethargy, mental fatigue, low mood and/or depression, weight gain, sensitivity to cold, cold extremities, hair thinning and loss of eyebrow hair in the outer margins.

In an effort to stop this happening, thyroid hormone levels are monitored in the brain. If the levels of these fall, the pituitary gland (at the base of the brain) is instructed to secrete a hormone known as thyroid stimulating hormone (TSH) which is designed to instruct the thyroid to produce more thyroid hormone. As thyroid hormone levels go up, this is sensed by the brain, which then reduces its production of TSH. This mechanism is believed to maintain adequate thyroid hormone levels in the majority of individuals.

However, if for whatever reason the thyroid fails to produce sufficient thyroid hormone levels, TSH levels may continue to rise, to the point that they become higher than normal. This finding, coupled usually with a low T4 level in the blood, is used generally used to diagnose low thyroid function (hypothyroidism). Sounds good so far, except that there are a number of reasons for why someone’s TSH level may not always be relied upon to give a definitive measure of someone’s true thyroid status.

One reason concerns the ‘normal’ ranges of hormones themselves. Some individuals believe that these are simply set too wide. What is regarded as ‘normal’ is essentially arbitrarily set. Many labs here in the UK set an upper limit of normal of TSH of 4.0 mU/L. However, other labs, I have noticed, set an upper limit of more than 5. Last week I saw a patient who came with a previous blood result from last year that stated an upper limit of 5.6. And now consider this: some years ago the American Association of Clinical Endocrinologists recommended that the upper limit of TSH be lowered from 5.0 to 3.04. Overnight, as a result of this change, the number of individuals who could be classified as hypothyroid on the basis of their TSH level more than quadrupled.

Now, if assessing thyroid status with TSH levels is such a precise art, how is it that upper limits of TSH vary so widely?

Another reason why TSH may not reflect true thyroid status relates to the fact that the brain and peripheral tissues (outside the brain) can sense thyroid hormone levels different. Imagine, for a moment, that the tissues in the periphery are somewhat resistant or ‘numb’ to the effects of thyroid hormones (in a way similar to the situation when tissues become resistant to insulin). But let’s imagine there is no such problem in the brain. Then what can happen is the brain thinks there’s enough thyroid hormone around, while the rest of the body is in fact deficient in thyroid hormone and therefore exhibiting the symptoms and signs of hypothyroidism.

Even if the brain correctly senses a deficiency of thyroid hormone, that does not mean the pituitary will automatically respond appropriately. It is recognized that thyroid failure can be secondary to failure of the pituitary gland to produce sufficient TSH. This condition, known as secondary hypothyroidism, is traditionally characterized by low levels of TSH. However, it is possible that less severe failure of the pituitary may lead to ‘normal’ levels of TSH in individuals who have a genuine problem with hypothyroidism.

To my knowledge, none of these mechanisms have been nailed down. However, all of them, to my mind anyway, represent plausible explanations for how someone with signs and symptoms suggesting hypothyroidism can end up with ‘normal’ thyroid hormone test results.

Further doubt about the validity regarding ‘normal’ TSH levels comes from research which has linked higher TSH levels (though still within the ‘normal’ range) with an increased risk of weight gain and cardiac-related death. See the previous blog posts here and here for more about this.

So, bearing this in mind, I don’t think it’s too unreasonable that some practitioners do not to put their full and utter faith in conventional thyroid blood tests and their traditional interpretation when assessing thyroid status. It seems that some practitioners seem to be aware of the limitations of the traditional approach, and may prefer to treat the patient rather than the test results. It is, I believe, possible for individuals to present what looks, on the face of it, to be a clear case of hypothyroidism but, at the same time, yield ‘normal’ thyroid function tests. It is also possible for these individuals to find their health transformed on the initiation of thyroid hormone therapy.

Of course, there is a risk to treating with thyroid hormone, and they most certainly should not be doled out like sweeties. There is some thought, for instance, that thyroid hormone therapy can increase the risk of osteoporosis. However, if treatment is really surplus to requirement, then side effects such as a rapid pulse, undue anxiety and sleeplessness usually give this away.

And while there are risks to treating, what I think is sometimes forgotten is that there are risks associated with NOT treating too. Because if someone has genuine hypothyroidism (even if blood tests are normal), then not treating can consign them to a life of fatigue, low mood, depression and weight gain about which they often can do very little. Make no bones about it: undiagnosed and untreated hypothyroidism can have a devastating effect on health and quality of life.

Worse still, individuals with a genuine problem can end up being persuaded that, in the light of normal test results, their issues are all in their mind or perhaps simply due to ‘depression’. The suggestion appears to be that the tests can’t be wrong and that the doctors who treat such individuals must be. Are we to believe that individuals whose symptoms strongly point to low thyroid function improve out of sight on thyroid hormone therapy can only be exhibiting some glorified placebo response? Or perhaps their recovery was just a figment of their imagination. Or their doctor’s. Silly people.

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