The results of a double-blind study crossover trial of thyroid drugs were published in the March 2005 Archives of Internal Medicine . The study, which was conducted in Spain, compared levothyroxine/T4 treatment for hypothyroidism, versus 2 different combinations of levothyroxine plus synthetic T3 (known as liothyronine).
The study included 28 women (2 of whom later dropped out). 14 of the women took 100 mcg of levothyroxine for 8 weeks, while the other 14 took "combination treatment" -- 75 mcg of levothyroxine plus 5 mcg of T3 -- during the first 8 weeks. During the next 8-week period, each group of 14 "crossed over" to take the opposite regimen. The final 8 week period all the patients received what they called "add-on combination treatment" -- which consisted of 87.5 mcg of levothyroxine, plus 7.5 mcg. of T3.
The researchers evaluated a variety of quality of life, psychometric and physiological measurements, and concluded that there was no evidence of improvement for patients on the combination or add-on combination treatments, compared to the T4-only treatment.
Interestingly, however, despite there being no "objective" evidence of improvement, 12 patients preferred the combination treatment, 6 patients preferred the add-on combination treatment, only 2 patients preferred standard treatment, and 6 patients had no preference.
To summarize, then:
- 12 (46%) preferred combination (75 mcg levothyroxine/ 5 mcg liothyronine-T3)
- 6 (23%) preferred add-on combination treatment ( 87.5 mcg of levothyroxine, plus 7.5 mcg of T3)
- 2 (8%) preferred standard treatment (100 mcg of levothyroxine)
- 6 (23%) had no preference
The researchers concluded that treatment of hypothyroidism with levothyroxine alone is sufficient. They state: "In summary, treatment with L-thyroxine–liothyronine combinations that replicate the ratio of thyroxine to triiodothyronine in human thyroid secretion does not offer any objective advantage over treatment with L-thyroxine alone, although patients prefer combination treatment. However, the addition of even minimally excessive liothyronine doses to L-thyroxine may have undesirable effects. Until clear advantages of L-thyroxine–liothyronine combinations are demonstrated, L-thyroxine alone should remain the drug of choice for hypothyroid replacement therapy."
Problems With the Study and its Implications
First, with an estimated 20 million plus patients with hypothyroidism in the U.S. alone, a study of only 28 women -- even if double-blind -- cannot be considered comprehensive or definitive. This is a very small sample, and as such, cannot have implications for the broad cross-section of the population of thyroid patients.
Second, the 28 patients selected for the study were all considered to have "overt hypothyroidism" because they had not had their dosages changed in the previous year, and had been maintained as "euthyroid" -- a TSH normal range. They were thought to have stable, non-fluctuating TSH levels for study-purposes. The study reported it was "unlikely that residual thyroid function interfered with our results." Unlikely perhaps, but not impossible. The patients' TSH, Free T4 and Free T3 had not been documented in the year before the study. All that was known was that they were maintained on one dosage of levothyroxine. Did those patients have a so-called "normal TSH" on that consistent dosage, or did thyroid levels fluctuate, showing evidence of residual thyroid function? Did they feel well on that consisten dosage? Were they symptomatic? None of this information was determined prior to the study. But 23 of the patients were hypothyroid due to thyroiditis (a condition that is notorious for fluctuating thyroid function), and 5 had received RAI for Graves' disease and toxic multinodular goiter, a treatment that in some patients does leave residual function. Simply choosing patients who had stayed on the same dose for a year does not make for a "stable" population of thyroid patients for study purposes.
>> Read about other problems with the study, the main concerns, and next steps
