Thyroid: T4 only vs. T4/T3 Combo Therapy

When discussing the best medication to help optimize and improve thyroid, there is not a “one size, fits all” solution. Various patients often must take various medications and different brands to truly get their thyroid levels to improve to a point that they feel better and have better clinical outcomes. This can be a bit of a challenging task to take on from a provider’s standpoint but even more of a challenge as the patient. Often, patients will see their family provider or endocrinologist and they will be prescribed the “stand of care” which is Levothyroxine also known as Synthroid®. Due to cost, many patients usually stick with generic levothyroxine and often are left with levels that are “normal” but still very clinically symptomatic of an underactive thyroid. The question patients should be asking is “why?”. “Why is that if my thyroid levels are now normal, I don’t feel any better or in some cases feel worse?” To understand this, it is important to have a basic understanding of the thyroid and pituitary gland as well as what levothyroxine is and how it works in the body.

First, it is important to have a basic understanding of how the thyroid works in respect to lab tests and what they reveal to your clinician. Often, the first lab that indicates a disruption in thyroid regulation is the thyroid stimulating hormone (TSH) level. This is usually performed as part of a yearly physical exam and is produced by a gland in the brain called the pituitary gland. The hormone, TSH, is designed to stimulate the thyroid. If the thyroid is not working, then the brain (pituitary gland) is going to produce more of this hormone and thus a high TSH lab result usually indicates a low functioning thyroid or hypothyroidism.  Now, let’s look at the actual thyroid hormones themselves. Often a thyroxine or T4 level is checked in addition to a TSH. Thyroxine, T4, has 4 iodine molecules and is the stored version of active thyroid hormone, T3. T3 is mostly converted from T4 but the thyroid gland does make some T3 on its own. The TSH is regulated by the level of T4 floating throughout the circulation. If T4 is low, TSH will be high and vice versa. In circulation, when there is a need for active thyroid hormone, the body removes an Iodine molecule making the hormone triiodothyronine or T3. When thyroid hormone is in its active state, it can bind to receptors in various cells allowing them to perform the metabolic actions that the thyroid helps to control such as fatty acid metabolism, hair growth, heart rate and body temperature regulation.

Now that there is a basic understanding of thyroid function in the body, it is important to understand what happens when we give a medication for thyroid. Levothyroxine is the synthetic compound of T4 that a patient takes to help correct an underactive thyroid. The idea is that by giving the body more T4 this will allow more conversion to T3 thus increasing active thyroid hormone and lower TSH. While this makes sense from a chemical perspective, in the human body, this doesn’t always occur. Humans don’t live in a bubble and don’t live in an environment where all variables can be controlled. Often, as a response to stress the body will convert T4 into an inactive form of T3 called Reverse T3. This can be life and situational stress as well as metabolic stress. When we give a patient T4 or levothyroxine, we suppress their own thyroid by suppressing TSH (Not that the thyroid was working well to begin with). In doing so, we are now relying on the body to convert 100% of the active thyroid hormone T3 from the synthetic T4. If this does not occur and leads to more conversion to Reverse T3 the patient will often have minimal symptom improvement or in many cases feel worse. Due to this fact, many clinicians have changed the way they approach thyroid by giving a patient a combination of T4 and T3. The synthetic form of T3 is a medication called Liothyronine or Cytomel®. By combining T4 and T3, patients will often have improved symptoms and better outcomes regarding their thyroid regulation.

Next post, will discuss some of the things to be aware of when adding T3 to a treatment regimen as well as glandular based or “Natural” thyroid medications such as Armour® Thyroid, NP Thyroid®, etc.