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Taking T3 & T4 Together: Better for Some Patients

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Travis Bowman, Staff Writer
Thyroid Nation

Do You Take A T4 and T3 Medicine Like Armour or Nature-Throid?

Good news for Hypothyroid sufferers’ who continue to struggle with symptoms while only taking T4 (Levothyroxine/Synthroid). In a groundbreaking study by the European Journal of Endocrinology, it’s being reported that combination of T4 and T3 is superior than that of only taking T4 in some patients.

This report is somewhat controversial because while some studies have shown improvement with the combination of these drugs, many studies in the past have not shown this conclusion, but may have been biased toward a T4 only therapy. 

In any case, in the new research, Danish researchers conducted a double-blind, randomized cross-over study — which is considered the gold standard format for research — of 59 patients. In the patient group, 50 micrograms of the usual T4 dose was replaced with either 20 mcg of T3 or 50 mcg of T4 for 12 weeks. The patients then did the “cross-over,” doing the opposite for another 12 weeks. The T4 dose was regulated if needed to keep the TSH levels stable.

Tests for quality of life (QOL) and depression were performed at the start, and after both of the 12-week treatment periods. The quality of life and psychological factors evaluated included, among other factors: general health, social functioning, mental health, vitality, sensitivity, depression, and anxiety.

What the researchers found was that among the patients — 55 of whom were women — there were significant differences in 7 out of 11 of the QOL and depression scores, showing a positive effect related to combination T4/T3 therapy.

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

The researchers concluded that, in a study where TSH levels were kept consistent, the T4/T3 combination therapy that included 20 mcg of T3 daily was superior to levothyroxine-only treatment, when evaluating for a number of quality of life measurements, depression and anxiety scales, and patient preference.

The report continues to say that the T3 side effects while in combination therapy were less than those side effects experienced by those taking only the T4. 

The researchers have said that their study suggests that a subgroup of patients appear to benefit from the combined T4/T3 therapy. In particular, they suggest that there may be physiologic reasons why the subgroup responds to — or needs — the T3, specifically, that:

…a recently identified polymorphism in the gene coding for the type two deiodinase, the enzyme responsible for the regulation of T3 availability to the tissues, has been proposed in order to help identifying subgroups more likely to benefit from T4/T3 combination therapy. Another polymorphism, located in OATP1C1, a thyroid hormone transporter expressed at the blood-brain barrier, has been associated with fatigue and depression.

Famed Dutch Endocrinologist Wilmar Wiersinga says in his editorial that more trials are needed but that signs are pointing to a drug combination scenario for the relief of some people.  

Dutch endocrinologist Wilmar Wiersinga wrote an accompanying editorial, titled “Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?”

According to Dr. Wiersinga, some previous studies had concluded that there is no benefit to adding T3. Yet, the fact that, according to Wiersinga, as many as 10% of hypothyroid patients are dissatisfied with how they feel on what doctors would call an “adequate dose” of levothyroxine replacement led to the publication of the Danish study.

TNE-Banner-Ad-Free-ShippingThe editorial, which is published in full-online, points to flaws in the previous studies and analyses of T4/T3 combination therapy. Dr. Wiersinga concludes that there are two strong reasons to conduct additional randomized controlled trials comparing levothyroxine/T4 only treatment monotherapy, to T4/T3 combination therapy: First, trials so far have been largely unsuccessful in mimicking physiological serum FT4-FT3 ratios throughout 24 h.

The development of sustained-release T3 preparations might be essential for reaching the goal of ‘physiological’ thyroid hormone replacement. Secondly, an increasing number of polymorphisms in deiodinases and thyroid hormone transporters are associated with psychological well-being, depression, fatigue, and preference for combination therapy. Could it be that subjects not satisfied with monotherapy are frequent carriers of these polymorphisms, and will have a better response to combination therapy?

According to Dr. Wiersinga, development of a sustained-release T3 preparation, given as a single nighttime dose (together with levothyroxine once daily) might best maintain physiological ratios of Free T4 and Free T3 in in some thyroid patients over a 24-hour period.

About the Author

Author-Travis-Thyroid-NationTravis Bowman is a staff writer for ThyroidNation.com. Living with his wife and 2 children, he has a front row seat to the devastation thyroid disease can cause and offers an in-depth, up close and personal view of his experience.  His wife of 18 years suffers from Hypothyroidism and was diagnosed with Hashimoto’s Thyroiditis and Adrenal Fatigue in 2012. Seeking help, offering compassion and supporting cures for those that suffer, he is on a mission to educate the masses.

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