The T4/T3 Thyroid Drug Controversy

Thyroid Hormone Replacement With T4 and T3 Drugs Vs. Levothyroxine Alone

The conventional, guidelines-approved treatment for hypothyroidism is thyroid hormone replacement with a synthetic form of the thyroid hormone thyroxine (T4). This synthetic thyroxine is known generically as levothyroxine. Some of the commonly-known brands are Synthroid, Levoxyl, Tirosint, and Unithroid. These are frequently referred to as "T4 drugs." 

There is increasing evidence, however, that some thyroid patients do not respond to the use of a T4-only therapy, and do better with the addition of the second thyroid hormone, triiodothyronine (T3). The synthetic form of T3 is known generically as liothyronine, and the key brand name is Cytomel. These are referred to as "T3 drugs." Natural, animal-derived forms of both T4 and T3 are also found in prescription Natural Desiccated Thyoid (NDT) drugs, made from the dried thyroid glands of pigs. The common brand names include Nature-throid, WP Thyroid, and Armour Thyroid. In the US, the generic is known as NP Thyroid.

As noted, the standard, conventional treatment for hypothyroidism is a levothyroxine drug alone. The addition of T3 to the levothyroxine/T4-only treatment -- or use of NDT drugs --  is a controversy, and the topic of ongoing research and discussion. This treatment controversy is explored in greater detail in the following key articles here at Verywell.

USA, New Jersey, Jersey City, Mature woman holding pill bottles
Tetra Images - Daniel Grill/Brand X Pictures/Getty Images

A groundbreaking 1999 study reported in the New England Journal of Medicine found the quality of life of thyroid patients life improved with the addition of a T3 drug to levothyroxine-only therapy.

The researchers determined that "treatment with thyroxine plus triiodothyronine improved the quality of life for most patients."Learn more about this important study.


tablets, pills, thyroid medication

The Journal of the American Medical Association (JAMA) reported in 2003 that a study found no benefit to patients when T3 was added to T4-only therapy. 

Read the study now (PDF)


thyroid drugs, thyroid medications

Dr. Ken Blanchard, MD, PhD, author of the book What Your Doctor May Not Tell You About Hypothyroidism critiques the 2003 JAMA study.

Read more about it now.


The May 2005 issue of the Journal of Clinical Endocrinology and Metabolism reported on a study that showed that hypothyroidism patients preferred a combination T4/T3 treatment to T4-only treatment. The researchers also found that combination treatment is associated with weight loss, while T4-only treatment is not.

"Patients preferred combined LT4/LT3 therapy to usual LT4 therapy... Decrease in body weight was associated with satisfaction with study medication...the outcome of this study does not preclude the possibility that a certain subgroup of patients may benefit from combined LT4/LT3 therapy."

Read about this study now.



A 2003 study conducted by the government, with patients at Walter Reed Medical Center, reported that Natural Desiccated Thyroid drugs were a safe alternative to levothyroxine-only therapy. 

Read more about this game-changing study now


comparing pills
comparing pills. istockphoto

A major study reported on in the European Journal of Endocrinology, looked at the controversial issue of treatment with synthetic T3 as a supplement to T4-only (levothyroxine) therapy for hypothyroidism.The study found that the combination of T4/T3 is superior to T4 only/levothyroxine treatment for hypothyroidism. 

A major finding: 

A total of 49% of the patients preferred the combination treatment, and only 15% preferred levothyroxine-only treatment.

 Read more about the study now



So many thyroid patients contact me here at Verywell, and at my Facebook Thyroid Support page, and ask the same question: "I'm on Synthroid (or another levothyroxine drug like Levoxyl) and I don't feel well. What else can I do?" What I tell fellow thyroid patients is that in this situation, the first thing you'll want to think about is whether or not you might benefit from the addition of supplemental T3.

Find out the answer now.


white pills
white pills.

If you are on thyroid hormone replacement drugs (i.e., generic levothyroxine, or the Synthroid, Levoxyl, or Tirosint brands) and are not feeling well, one possibility is that you may benefit from adding T3, or switching to a thyroid medication that includes T3.

Learn more about the potential benefits of T3 or NDT treatment


New Research

One promising note in the debate over T4-only versus T3/T3 combination treatment for hypothyroidism is a large research study being planned in 2016. This study will look at a variety of parameters -- including quality of life and patient satisfaction -- along with a regular schedule of blood tests, comparing levothyroxine against levothyroxine plus T3, and also comparing these two therapies against natural desiccated thyroid treatment. The study is also evaluating the prevalence of a genetic variation - known as a polymorphism -- that may make T3 more effective -- or even necessary in some hypothyroid patients. This multi-center, double-blind, peer-reviewed study, which is being designed and administered by some of the nation's leading endocrinologists, and conducted through top medical centers and hospitals, is not funded by any pharmaceutical companies.

When the results are published, this study has the potential to dramatically change the official hypothyroidism treatment guidelines, by demonstrating that levothyroxine/T4, T4/T3 combination therapy, and NDT treatment are equally safe and effective. The study may also demonstrate that the addition of T3 results in improved quality of life for some -- or even the majority -- of patients. The study should also show if the genetic polymorphism is linked to the need for T3 as part of the therapy. Stay tuned for more information!

Continue Reading