Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary Hypothyroidism

Abstract

T(4) is standard treatment for hypothyroidism. A recent study reported that combined T(4)/liothyronine (T(3)) treatment improved well-being and cognitive function compared with T(4) alone. We conducted a double-blind, randomized, controlled trial with a crossover design in 110 patients (101 completers) with primary hypothyroidism in which liothyronine 10 micro g was substituted for 50 micro g of the patients' usual T(4) dose. No significant (P < 0.05) difference between T(4) and combined T(4)/T(3) treatment was demonstrated on cognitive function, quality of life scores, Thyroid Symptom Questionnaire scores, subjective satisfaction with treatment, or eight of 10 visual analog scales assessing symptoms. For the General Health Questionnaire-28 and visual analog scales assessing anxiety and nausea, scores were significantly (P < 0.05) worse for combined treatment than for T(4) alone. Serum TSH was lower during T(4) treatment than during combined T(4)/T(3) treatment (mean +/- SEM, 1.5 +/- 0.2 vs. 3.1 +/- 0.2 mU/liter; P < 0.001), a potentially confounding factor; however, subgroup analysis of subjects with comparable serum TSH concentrations during each treatment showed no benefit from combined treatment compared with T(4) alone. We conclude that in the doses used in this study, combined T(4)/T(3) treatment does not improve well-being, cognitive function, or quality of life compared with T(4) alone.

Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

“…In the study by Appelhof et al (16), serum TSH at the time of evaluation was mean 0.64 mU/l in the T 4 -treated group, but 0.35 mU/l in the T 4 :T 3 ratio of 10:1 group, and 0.07 mU/l in the 5:1 group, the differences being statistically significant (P!0.01). In the study by Walsh et al (10), mean serum TSH at the time of evaluation was 1.5 mU/l in the T 4 -treated group, but 3.1 mU/l (P!0.001) during the combination therapy period (10). Finally, in the study from Saravanan et al (17) median serum TSH was 0.78 mU/l during T 4 monotherapy compared to 1.21 mU/l during combination therapy (P!0.001).…”

“…The authors were unable to demonstrate any differences in mood, fatigue, or psychological symptoms. The second study by Walsh et al (10), included 101 patients treated in a cross-over, double-blind design exchanging 50 mg of T 4 with 10 mg of T 3 (ratio 5:1). No differences of cognitive function, QOL scores or thyroid disease-related symptoms were found.…”

“…In four previous studies patients' preference was also assessed (10,16,17,19). In one study using high doses of T 3 (40-60 mg), the monotherapy regimen with T 4 was preferred (19).…”

“…In one study using high doses of T 3 (40-60 mg), the monotherapy regimen with T 4 was preferred (19). One study (10) did not find any preference, whereas in two studies (16,17) combination therapy was preferred: in the study by Appelhof et al (16), combination therapy was preferred by 41% in the T 4 :T 3 ratio 10:1 group and by 52% in the T 4 :T 3 ratio 5:1 group, as compared to 29% of the T 4 monotherapy group (PZ0.024, both combination groups). In this study, a significant decrease in body weight was found and the decrease in weight correlated with increased satisfaction with study medication.…”

“…However, the studies included in the meta-analysis were a mixture of different patient groups, including patients with previous thyroid cancer, autoimmune hypothyroidism, and subclinical as well as overt hypothyroidism. One of the largest studies was a randomised, double-blind crossover study including 101 patients (10). However, the authors were unable to keep serum TSH levels at a similar level in the two treatment groups, mean serum TSH being 3 in the combination group and 1.5 mU/l in the monotherapy group (P!0.001).…”