“Why do I feel bad despite a normal thyroid test?” you wonder. You ask your physician. “Your thyroid test is normal. Therefore, your symptoms cannot be due to hypothyroidism,” your physician replies in an authoritative tone. You feel annoyed and frustrated that your physician is not listening to you. On the other hand, your physician honestly believe that your symptoms are not due to hypothyroidism, because their blood test is within the normal range. This obviously leads to frustration, both for patients as well as their physicians.
Is it possible that you may actually be hypothyroid while your thyroid test is in the normal range? Let’s take a closer at this question.
Many physicians check TSH only to assess if your thyroid hormone level is normal or not. Why? Because this is what they have been taught to do. It is an inexpensive way to evaluate your thyroid hormone level, but it is not very scientific and often leads to an inaccurate assessment. So, if your TSH is in the normal range, your physician is confident that your thyroid hormone dose is good and your symptoms cannot be due to hypothyroidism. In fact, this kind of assumption is not very scientific. It will become clear to you as I elaborate on this very common misconception.
Normal TSH Does NOT Always Mean Normal Thyroid Function
TSH stands for Thyroid Stimulating Hormone. This is a hormone produced by the pituitary gland in response to the T3 level inside the pituitary gland. There is an inverse relationship between TSH and T3 level. Consequently, if your pituitary gland senses T3 to be low, it produces more TSH, which is a message for the thyroid gland to produce more thyroid hormone. Conversely, if T3 is high, then the pituitary gland produces less TSH, telling the thyroid gland to produce less thyroid hormone. In this way, the pituitary gland tries to regulate thyroid hormone production by the thyroid gland.
Often, patients mistakenly think TSH is their thyroid hormone. So, when they see low TSH on their Lab report, they think their thyroid hormone is low. In fact, their thyroid hormone may be high.
The Normal Range Of TSH Is Inaccurate
The so-called normal range of TSH is 0.4 – 4.50 mIU/L, which is not actually correct for many individuals. This range should be 0.3 – 2.0 mIU/L, a fact most endocrinologists know. However, laboratories continue to stick to the range of 0.4 – 4.50 mIU/L. Not too long ago, laboratories used to give a normal range as 0.4 – 5.50 mIU/L. It took them many years to bring the upper limit down from 5.50 to 4.50. It may take another decade before they bring the upper limit down to 2.0. In the meantime, you don’t have to suffer from the stubborn attitude of the laboratories. Remember, normal range of TSH is 0.3 – 2.0 mIU/L.
Therefore, if your TSH is 3.8 mIU/L, your physician may be erroneously confident that your thyroid hormone is fine, but in fact, you may be low on thyroid hormone. In most of my patients, I aim for TSH to be below 2 mIU/L.
You also need to understand that a normal range simply refers to the general population. It is just a guideline, not an absolute fact for your body. For example, a TSH of 1.9 mIU/L may be normal for someone else in the general population, but not for you. Maybe a TSH level of 0.6 mIU/L is normal for you. Obviously, you will continue to suffer from symptoms of hypothyroidism at a TSH level of 1.9 mIU/L, even though it is in the normal range. In fact, your TSH needs to brought down further by increasing the dose of your thyroid pill. I have seen a dramatic improvement in some of my patients’ symptoms, once I brought their TSH below 1 mIU/L.
Your TSH May Be In The Normal Range While You Are Actually Hypothyroid
Your TSH is a reflection of what is going on in your pituitary gland, not necessarily what is happening in the rest of your body, such as your muscles, skin, fat, liver, kidneys and heart. Therefore, your pituitary may be normal, but not the rest of the body, as far as the thyroid hormones are concerned.
In addition, there are a number of conditions which prevent the usual rise in TSH due to hypothyroidism. Consequently, your TSH may be within the normal range while your are actually suffering from hypothyroidism.
TSH may also be low if your pituitary gland is unable to produce TSH to begin with. This happens in people who undergo surgery or radiation to the pituitary and hypothalamic area in the brain.
Sometimes, a large pituitary tumor or large doses of steroids may also cause TSH to be low. At times, the pituitary may undergo degeneration due to infections or acute hemorrhage, which causes TSH to be low.
Low TSH then leads to low thyroid hormone production by the thyroid gland. Your physician may mistakenly interpret low TSH as a sign of too much thyroid hormone (hyperthyroidism), and may inappropriately lower the dose of your thyroid pill.
If the cause of hypothyroidism is in your pituitary gland, we call it secondary hypothyroidism, as compared to primary hypothyroidism, when the cause is in your thyroid gland. We call it tertiary hypothyroidism if the cause is in your hypothalamus. It is only in primary hypothyroidism that your TSH may be high. However, your TSH is typically low or low normal if you have secondary or tertiary hypothyroidism.
Free T4 stands for Free Thyroxine level in the blood. This is another fairly common blood test that many physicians order to evaluate the thyroid status of their patients.
You May Be Hypothyroid Even When Your TSH and Free T4 Are In The Normal Range
Let’s say your physician checks your Free T4 in addition to TSH and both of these tests turn out to be normal. Now, your physician may be extra confident that your symptoms cannot be due to hypothyroidism. Really? A normal Free T4 does not always means your thyroid function is normal. Here is why:
Almost all T4 circulates in the blood bound to carrier proteins and is inactive. Only a tiny fraction (0.03%) of the total T4 circulates as unbound or Free T4. This Free T4 is available to tissues, but the Free T4 is still not active. It has to be converted to T3, which is the active thyroid hormone. Why? Because thyroid hormone has to bind to a receptor inside the nucleus of a cell in order to carry out its functions. This receptor is called the Thyroid Hormone Receptor (THR). Inside the cell, it is T3 and not T4 that binds to the THR. That’s why T3 and not T4, is the true active thyroid hormone. Therefore, your blood level of Free T3 (and not Free T4) reflects what is going on inside the tissues.
Most physicians treat their hypothyroid patients with T4-only therapy (Levothyroxine with brand names Synthroid, Levoxyl, Unithroid, etc). Why? Because this is what they have been trained to do. They have been told that T4 gets converted into T3. Therefore, T4-alone therapy should be adequate. Most physicians follow this recommendation without ever testing or questioning this myth.
In a scientific way, let’s examine if the drum beat of T4-only therapy holds any water. Here are some basic facts in thyroidology that no knowledgeable endocrinologist would refute:
T3 in the blood comes from two sources: About 20% of it comes directly from the thyroid gland. The remaining 80% of T3 comes from T4 to T3 conversion. Obviously, if you are on T4-only therapy, your T3 level is 20% lower to begin with.
T4 to T3 conversion takes place due to an enzyme called 5′ deiodinase, which is of two types: Type 1 and Type 2. Type 1 deiodinase is present in the peripheral tissues such as skin, muscles, bones, liver, kidneys and heart. Type 2 deiodinase is present inside the pituitary gland and the rest of the brain.
If your Type 1 deiodinase is not working normally, your T4 to T3 conversion will be inadequate. There are many common conditions that interfere with the normal functioning of Type 1 deiodinase, such as aging, diabetes, stress, surgery, infections, any chronic illness and certain drugs such as steroids. The net result? T3 in the tissues will be low and you will actually be hypothyroid even though your Free T4 may be normal.
Type 2 deiodinase present inside the pituitary gland is responsible for T4 to T3 conversion inside the pituitary gland. It is this intra-pituitary T3 that regulates the amount of TSH in a reciprocal fashion: low intra-pituitary T3 leads to high TSH and vice versa, high intra-pituitary T3 leads to low TSH.
Inside your pituitary gland, T4 to T3 conversion, carried out by Type 2 deiodinase usually stays normal. Therefore, your T3 inside the pituitary gland will be normal if your Free T4 in the blood is normal, as is the case when you are on adequate dose of T4-only therapy. With T3 in the pituitary being normal, your pituitary gland will think that your thyroid hormone is normal and will produce the normal amount of TSH. In this way, your TSH will be in the normal range, even though your T3 may be low in peripheral tissues (such as muscles, skin, bones, heart, liver and kidneys), and you are actually hypothyroid. However, your physician, in all honesty, will think your thyroid is perfectly normal because your Free T4 and TSH are normal. It is not your physician’s fault. This is what they have been taught.
Another interesting observation: Your serum Free T4 abruptly rises by about 20% when you fast for 12 or more hours . In clinical practice, many patients actually fast for 12 or more hours because they also have their blood drawn for cholesterol, triglycerides and glucose level. This increase in Free T4 is misleading in the sense that it does not truly reflect what happens on a daily basis when you do not fast. You may actually be low in Free T4, but fasting will bring Free T4 in to the normal range. The reason for this abrupt increase in Free T4 after fasting is as follows: Fasting causes a decrease in the peripheral T4 to T3 conversion which causes a transient build-up of Free T4. Therefore, next time you go for a fasting blood test which includes Free T4, do not fast more than 6 – 8 hours, which is actually enough for the measurements of your cholesterol, triglycerides and blood glucose as well.
Free T3 stands for the level of Free T3 in your blood. Most T3 circulates in the blood, tightly bound to proteins. Only a tiny fraction, 0.3% of total T3, is present as Free T3. It is this free fraction that is available to tissues and is the active thyroid hormone.
You May Be Hypothyroid Even When Your TSH, Free T4 And Free T3 Are In The Normal Range
Some conscientious physicians may even check your Free T3 in addition to Free T4 and TSH. When you are on T4-only therapy, typically your serum Free T4 level is in the upper half of the normal range (high normal), and your Free T3 is in the lower half of the normal range (low normal) for the two reasons I mentioned above: Lack of the 20% of T3 which normally comes directly from the thyroid, and inadequate T4 to T3 conversion in the peripheral tissues in a lot of individuals.
Remember, your Free T3 and not Free T4 reflects your tissue level of thyroid hormone.