Health & Medical Ear & Nose,Throat

Study Finds Patients Prefer Combination T4/T3 Treatment

Updated August 18, 2014.

It's common knowledge among patients, and some medical professionals, that a substantial number of patients with hypothyroidism will continue to have various complaints and symptoms, despite treatment with levothyroxine that maintains so-called "normal" TSH levels. One study in 2002 found that, (Saravanan et. al. Psychological well-being in patients on ?adequate? doses of l-thyroxine: Clin Endocrinol (Oxf) 57:577?585), compared with controls, more than 13% was not satisfied with their health condition, reflecting dissatisfaction with their treatment.

The primary complaints were fatigue, weight gain, body aches/pains, and clumsiness.

According to the Bente C. Appelhof, MD, from the University of Amsterdam in the Netherlands, and colleagues: "Controversy remains about the value of combined treatment with LT4 and LT3, compared with LT4 alone, in primary hypothyroidism. It is a well-known clinical notion that a fair proportion of patients with hypothyroidism remains with health complaints, despite substitution therapy with levothyroxine and normalization of serum TSH [thyroid-stimulating hormone] values."

Other animal studies have shown that replacement therapy with levothyroxine (LT4) alone does not ensure euthyroidism -- normal thyroid levels -- in all tissues. Instead, euthyroidism could only be achieved by a combinated treatment of LT4 and liothyronine (LT3). Various studies have focused on this issue, looking at whether LT4 therapy might not be enough to restore euthyroidism in human tissues as well. While patients consistently report a preference for the combined studies, researchers have not been able to isolate specific improvement factor that are clinically measurable.

Now, researchers have identified at least one factor that appears to be related to combination therapy -- weight loss.

Research published in the May 2005 issue of the Journal of Clinical Endocrinology and Metabolism reported on a recent study that found that patients preferred thyroid treatment that included a combination of levothyroxine (T4) and T3, rather than the usual levothyroxine (T4 only) treatment, and that combination treatment was associated with weight loss. This clinical trial is the largest to date, and the first since the Bunevicius study published in the New England Journal of Medicine in 1999 that confirms a beneficial effect of combination T4/T3 therapy for hypothyroidism.

The double-blind, randomized, controlled clinical trial looked at 141 patients with primary autoimmune hypothyroidism, who were broken into groups who were treated with T4/T3 in a ratio of 5:1, 10:1, as well as a group that continued with their previous T4-only treatment. After 15 weeks, the study showed a clear preference on the part of the patients for the combination treatments, and in particular, the 5:1 treatment featuring a higher level of T3, versus the T4-only treatment.

Some particular findings of interest:
  • A decrease in body weight -- but not a decrease in serum TSH -- was correlated with increased satisfaction with study medication.
  • In both combination groups, there was a decrease in weight, most pronounced in the 5:1 ratio group, who had a mean decrease of 1.7 kg, or 3.75 pounds. Theh 10:1 group had a mean weight loss of 1 pound. The T4-only group had no change in weight.
  • Of the patients who preferred combined therapy, 44% had serum TSH less than 0.11.
  • Measurable changes in mood, fatigue, well-being, and neurocognitive functions could not be identified to explain the patient preference for the combination treatment.
One key flaw in the study was that some patients receiving combination treatment were receiving suppressive doses, which is considered overtreatment. They had TSH levels below the normal range, and would therefore be considered hyperthyroid.
"Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy," the authors write. "Decrease in body weight was associated with satisfaction with study medication."

While the study authors could not find any measurable reason to recommend the combination therapy, they did conclude: "Nevertheless, the outcome of this study does not preclude the possibility that a certain subgroup of patients may benefit from combined LT4/LT3 therapy."

Source: Appelhof BC, et. al. "Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial." J Clin Endocrinol Metab. 2005 May;90(5):2666-74.

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