Levothyroxine vs. Combination T4/T3 Therapy for Hypothyroidism

There is ongoing debate about which is more beneficial

By Mary Shomon | Medically reviewed by a board-certified physician
Updated March 17, 2019

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Treating your underactive thyroid gland with thyroid hormone replacement medication is essential for your body to function. While treatment with synthetic thyroxine (T4), called levothyroxine, is the standard of care for hypothyroidism, for certain patients, combining T4 with triiodothyronine (T3)—another thyroid hormone—may be a reasonable approach. This, however, is not without debate within the medical community.

The Standard of Care (T4)

The guidelines-approved treatment for hypothyroidism is thyroid hormone replacement with a once-daily dose of synthetic thyroxine (T4), also referred to as l-thyroxine or L-T4.

Besides a generic form, levothyroxine is also available in the United States under the brand names Synthroid, Levoxyl, Tirosint, and Unithroid.

If too much levothyroxine is given (called T4 over-replacement), hyperthyroidism may develop. Keep in mind, though, that this side effect is rare. If it does occur, it can usually be easily fixed with a dose adjustment.

Adding Liothyronine (T3)

Some doctors recommend taking T3 (triiodothyronine) in addition to T4 for the treatment of hypothyroidism (that is, two separate pills). Liothyronine, known by the brand name Cytomel and Triostat, is the synthetic form of T3.

The problem with T3 is that it has a very short lifespan, so it needs to be taken several times a day. Due to these required multiple daily doses, T3 levels fluctuate in the body; when T3 levels are high, symptoms of hyperthyroidism often occur.

Symptoms of hyperthyroidism include a fast heart rate, insomnia, and anxiety. A type of heart arrhythmia called atrial fibrillation and bone loss (osteoporosis) may also occur.

Combination T4/T3 Options

Besides taking separate pills for T4 and T3 replacement, there are combination T4/T3 preparations that are taken only once a day.

Two such preparations available in the United States are:

  • Natural desiccated thyroid (NDT)
  • Thyrolar (Liotrix)

Many experts, however, do not see these options as being the same as taking T4 and T3 independently.

Natural Desiccated Thyroid

Natural desiccated thyroid (NDT) hormone is a drug derived mainly from the dried glands of pigs. It's also called natural thyroid, thyroid extract, porcine thyroid, pig thyroid, and known by the brand names Armour Thyroid and Nature-throid.

NDT contains both T4 and T3; however, the ratio of T4:T3 in NDT is not the same as the ratio of thyroid hormone in humans. Moreover, the amounts of T4 and T3 can vary from batch to batch of NDT—and this can affect the stability of thyroid hormone levels in your body.

Thyrolar (Liotrix)

Thyrolar (Liotrix) is another combination T4/T3 preparation. Thyrolar contains much more T3 that what is normally made within the body, which is what allows it to be effective despite only being taken once a day. However, this high dose of T3 can cause symptoms of hyperthyroidism.

What's Right for You?

The vast majority of endocrinologists advise levothyroxine over combination T4/T3 for the treatment of hypothyroidism—and the primary reason is to avoid the hyperthyroid effect. When taking T3, it's simply impossible to avoid "T3 spikes," which can lead to unpleasant hyperthyroid symptoms, like anxiety or a rapid heart rate.

This all said, if you have persistent hypothyroid symptoms on levothyroxine, your doctor may recommend a three-to-six-month combination T4/T3 trial. Research suggests that a subgroup of hypothyroid patients on levothyroxine continue to have symptoms (fatigue, difficulty losing weight, etc.) despite normalization of their TSH and thyroid hormone levels.

Of course, prior to prescribing combination T4/T3, your doctor will want to ensure your symptoms are not due to another medical condition that mimics hypothyroidism, such as depression, anemia, or fibromyalgia.

Moreover, if you are pregnant and hypothyroid, levothyroxine (not combination T4/T3 therapy) is the advised treatment, regardless if you have persistent symptoms.

Excess T3 in a pregnant woman may cause hypothyroxinemia in the developing fetus, which is associated with potential neurological problems.

A Word From Verywell

The big picture for you or a loved one is to understand that, as of now, the standard treatment for hypothyroidism is a T4 drug alone. Though the addition of T3 continues to be a topic of ongoing research and debate within the thyroid community, for certain patients, it may be a sensible strategy.

Right now, the best thing you can do for your thyroid care is to carefully talk through your options with your doctor. Remember, as well, that optimizing your thyroid hormone levels can be a trial and error process—especially in the beginning. Try to remain patient as your treatment plan is honed.

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