Levothyroxine does not work in many patients with hypothyroidism, even when you are taking the correct dose the first thing in the morning, and there is no issue with its absorption. You wonder – what is going on? Upon recommendations from your endocrinologist, you switch from one brand of Levothyroxine to another. (Levothyroxine is available in its generic name as well as various brand names including Synthroid, Levoxyl, Unithroid, Euthyrox and Tirosint.)

However, your symptoms of hypothyroidism persist. Your physician checks your TSH and Free T4 which turn out to be in the normal range. However, you continue to suffer from hypothyroid symptoms. Now you and your physician are totally perplexed.

There are a lot of problems with this Levothyroxine  alone  approach. Often, it does not truly take care of your symptoms, because the approach itself is suboptimal and unscientific. Why?

Let me explain why Levothyroxine does not work in many patients with hypothyroidism.

1. Levothyroxine is a one-size-fits-all treatment approach

There are various causes of hypothyroidism. Therefore, one-size-fits-all is obviously an unscientific approach. Like other medical conditions, every person with hypothyroidism needs individualized treatment and not a machine-like, computerized approach. That’s why Levothyroxine does not work for everyone.

2. T3 – and not T4 (thyroxine) – is the active thyroid hormone

There are two thyroid hormones: T4 (tetra-iodothyronine or Thyroxine) and T3 (tri-iodothyronine). T4 has four iodine atoms and T3 has three iodine atoms.

The Levothyroxine approach aims to replenish low T4-state, while hypothyroidism is caused by low T3-state. Interesting, isn’t it?

The scientific fact: T4 does not carry out thyroid function in the tissues. It is simply a substrate – a precursor – for the formation of T3 inside the cell. After its formation, T3 binds to the Thyroid Hormone Receptor (THR) which is located inside the nucleus of the cell. Once T3 binds to the Thyroid Hormone Receptors, the thyroid hormone action sets in motion. That’s why T3 and not T4 is the true Active Thyroid hormone.

3. Presumption that Levothyroxine will Convert to T3 is Unscientific

The Levothyroxine approach makes a big presumption that Levothyroxine will properly convert to T3 in every individual. Nothing can be further from the truth.

Physicians who blindly follow this approach usually do not even check free T3 level in their patients to see if Levothyroxine is properly converting to T3 or not.  Very unscientific, isn’t it?

4. Levothyroxine Does Not Work if T4 to T3 Conversion is Impaired

Here is the scientific fact: T4 to T3 conversion in the peripheral tissues depends on the normal functioning of an enzyme called Type 1 Deiodinase. It may function normally in a young healthy person, but it often does not function normally in most individuals who have hypothyroidism. Therefore, Levothyroxine does not work in many patients as it does not convert into T3 efficiently.

A number of medical conditions can interfere with Type 1 Deiodinase. Subsequently, there is impairment of T4 to T3 conversion. Therefore, Levothyroxine may not provide adequate thyroid hormone replacement in individuals with these issues:

• Hashimoto’s Thyroiditis
• Obesity
• Stress
• Aging
• Diabetes
• Nutritional deficiencies
• Medications including beta-blockers and steroids

5.  Normal Thyroid Gland Produces T3 which Levothyroxine Cannot Compensate For

In normal individuals, about 20% of the daily production of T3 comes from the Thyroid gland itself and about 80% from the peripheral conversion of T4 to T3. This is a scientific fact which most physicians are not aware of. Sad but true!

Obviously, you will still be lacking 20% of T3 even if you have normal T4 to T3 conversion when you are on Levothyroxine treatment. This is another reason why Levothyroxine does not work in many patients.

6. TSH can be Incorrect as a Monitoring Test of Thyroid Hormone Replacement

The Levothyroxine approach recommends simply following serum TSH (Thyroid Stimulating Hormone) as the gold standard for the adequacy of thyroid hormone replacement, which can be an incorrect and misleading approach in a lot of individuals. Why? Let me explain.

TSH comes from the pituitary gland inside your brain. There is an enzyme called Type 2 Deiodinase in your pituitary gland,  which is responsible for the T4 to T3 conversion inside the pituitary gland. It is this T3 production inside the pituitary gland that is the main regulator of TSH production. In this way, TSH really tells whether your your pituitary gland is functioning normal or not. However, it may indirectly tell the state of your thyroid hormone production by the thyroid gland, only if your are a perfectly healthy person. Unfortunately, most physicians do not quite understand what I just explained and blindly follow TSH as the gold standard for the assessment of thyroid hormone replacement.

As I pointed out earlier, peripheral conversion of T4 to T3 is low in a lot of hypothyroid individuals, due to sub-optimally functioning Type 1 Deiodinase. However, their Type 2 Deiodinase continues to function normally, producing adequate amounts of T3 from T4 inside the Pituitary. Subsequently, TSH production is normal in these individuals, while their peripheral tissues are hypothyroid.

In other words, your pituitary is normal, but your peripheral tissues are actually hypothyroid. In this way, your Levothyroxine may treat the pituitary test (TSH), while you may have low thyroid in your peripheral tissues – muscles, skin, liver, heart, bones, etc. Your physician is satisfied as long as your TSH is normal. Sad but true!

This is another reason why Levothyroxine does not work in many hypothyroid patients.

7.  A low TSH does not Always Means Too Much Thyroid Hormone

Sometimes, even the Pituitary gland is not working normally for a variety of reasons and does not produce adequate amounts of TSH even when a patient is clearly hypothyroid. This can utterly confuse most physicians who have the mind-set that a low TSH always means too much thyroid hormone. Consequently, the physician may even decrease the dose of the patients’ thyroid hormone, thus making the poor patient even more hypothyroid.

One more reason why Levothyroxine does not work in many patients with hypothyroidism.

8. Levothyroxine Does Not Work and May Actually Worsen T3 Level

In a patient with underactive thyroid, there is a low production of T4 and T3 by the thyroid gland. Low T4 and T3 in the blood causes an increase in TSH production by the pituitary gland. The resulting high TSH level then tries to stimulate the thyroid gland to produce more T4 and T3.

When such a hypothyroid patient receives Levothyroxine – as is often the case – to normalize TSH, their high TSH-stimulus to increase T3 production goes away. Net effect is a decrease in T3 level and worsening of hypothyroidism. So, the patient actually feels worse after they receive Levothyroxine , although their physician may be satisfied because their TSH is now normal.

I have heard this sad story too many times.

“My life has gone downhill ever since I was placed on Levothyroxine. But, my physician does not believe me because my TSH is normal.”

Perhaps you now understand why Levothyroxine does not work in many patients. In addition, it may actually worsen hypothyroid state.

9. Levothyroxine Does Not Work Even If You Keep Increasing the Dose of Levothyroxine

In order to treat a patient’s symptoms, some physicians keep increasing the dose of Levothyroxine (T-4) to the point that the serum T4 level gets close to the upper limit of normal range. However, the patient continues to suffer from symptoms of hypothyroidism – weight gain, fatigue and somnolence – which may even get worse. Obviously, this frustrates both the patient and the physician.

Why do your symptoms of hypothyroidism fail to improve or even get worse when you are on a high dose of T4 treatment?  Let me explain.

As I pointed out earlier, Type 2 Deiodinase converts T4 to T3 inside your pituitary gland. In addition, it is also responsible for T4 to T3 conversion in your hypothalamus and the rest of the brain.

Now consider this. Your appetite center is located inside the hypothalamus. Due to a high level of T3 inside your hypothalamus, your appetite may get into turbo charge, causing you to gain more weight. Additionally, a high level of T3 inside your brain can lead to anxiety and insomnia, which often leads to day-time fatigue and somnolence. All of these symptoms – weight gain, fatigue and somnolence are common symptoms of hypothyroidism.

You wonder why your symptoms are getting worse. You ask your physician for some explanation. Physicians’ usual reply – “Your symptoms cannot be due to low thyroid as your TSH is normal.”

In Summary

Now you understand why Levothyroxine does not work in many patients. Treatment of hypothyroidism is pretty complex. For this reason, it requires an in-depth knowledge on the part of your physician to properly manage your underactive thyroid state. Simply putting every hypothyroid patient on Levothyroxine and then keep tweaking the dose based on TSH level is a superficial and unscientific approach!

Caution: You must never stop your levothyroxine or any other medication without first consulting your health care professional.

To learn more, please refer to my book, “Hypothyroidism and Hashimoto’s Thyroiditis” available at Amazon.