The T4/T3 Thyroid Drug Controversy

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 (and sometimes l-thyroxine, or L-T4). 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 brand name in the U.S. 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 Thyroid (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 controversial and the topic of ongoing research and discussion. This treatment controversy is explored in greater detail in the following key articles here at Verywell.

T3 Drugs Improve Quality of Life

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A groundbreaking 1999 study reported in the New England Journal of Medicine found that the quality of life of people being treated for hypothyroidism improved significantly with the addition of a T3 drug to their levothyroxine-only therapy.

The researchers determined that "treatment with thyroxine plus triiodothyronine improved the quality of life for most patients."

2003 JAMA Study Says T3 Offers No Benefit

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

Dr. Ken Blanchard on the T4/T3 Issue

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

T4/T3 Treatment Preferred by Patients in Study

The May 2005 issue of the Journal of Clinical Endocrinology and Metabolism reported on a study that showed that people with hypothyroidism 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."

Natural Desiccated Thyroid Drugs Deemed Safe

A 2003 study conducted by the U.S. federal government, evaluating hypothyroid patients at Walter Reed Medical Center, reported that natural desiccated thyroid (NDT) drugs were a safe alternative to levothyroxine-only therapy.

Danish Study Shows Added T3 Superior to T4-Only

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 key finding: 

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

Do You Need T3 To Feel Well?

So many thyroid patients contact us here at Verywell and at the 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 thyroid patients need to know is ask, in this situation, is: Would you benefit from the addition of supplemental T3?

Do You Need T3 or Natural Desiccated Thyroid?

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.

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 2018. 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 will also evaluate 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 hypothyroid 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!

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