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

Abstract

Background: Treatment of hypothyroidism with 3,5,3 0 -triiodothyronine (T 3 ) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T 3 . However, the analysis included a mixture of different patient groups and dose-regimens. Objective: To compare the effect of combination therapy with thyroxine (T 4 ) and T 3 versus T 4 monotherapy in patients with hypothyroidism on stable T 4 substitution. Study design: Double-blind, randomised cross-over. Fifty micrograms of the usual T 4 dose was replaced with either 20 mg T 3 or 50 mg T 4 for 12 weeks, followed by cross-over for another 12 weeks. The T 4 dose was regulated if needed, intending unaltered serum TSH levels. Evaluation: Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria: Serum TSH between 0.1 and 5.0 mU/l on unaltered T 4 substitution for 6 months. Results: A total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T 4 monotherapy versus T 4 /T 3 combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (PZ0.002). Serum TSH remained unaltered between the groups as intended. Conclusion: In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T 3 20 mg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.

Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?

“…The used questionnaires are the same in most but not all studies. Remarkably, the present study reports significantly better outcome of combination therapy in quality-of-life and depression scales (2), in contrast to all previous RCTs, except two early biased ones (5,6) and one (11) in which the benefit at 3 months was lost at 12 months. When asking the patients themselves, 49% preferred combination therapy and 15% monotherapy in the present study; 36% had no preference.…”

“…Although no relation was observed in the meta-analysis between the percentages of included athyreotic patients and the effect of combination therapy on symptoms, it is preferable to restrict inclusion to spontaneous autoimmune hypothyroidism as was done in the present RCT (2). Six studies in the meta-analysis had a crossover study design (5,6,7,10,12,13), and five studies had a parallel study design (8,9,11,14,15).…”

Psychosocial Factors in Patients with Thyroid Disease

“…Based on Grozinsky-Glasberg et al 's (2006) metaanalysis and Ma et al's (2009) systematic review it can be summed up that combined T4 and T3 treatment does not improve well-being, cognitive function, or health status compared with T4 itself. This is proved with works by Appelhof et al, 2005;Clyde et al, 2003;Joffe et al, 2004;Meng et al, 2004;Nygaard et al, 2009;Regalbuto et al, 2007;Saravanan et al, 2005;Sawka et al, 2003;Siegmund et al, 2004;Valizadeh et al, 2009;Walsh et al, 2003 and others. Whereas first works signalled differences in favour of combined T4 and T3 (Bunevičius et al, 1999(Bunevičius et al, , 2002Bunevičius & Prange, 2000).…”

Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

“…This raises the question of whether LT4-treated subjects with low T3 levels could benefit from low-dose LT3 therapy to assist with body weight regulation. However, all but one randomized controlled studies of combined LT4/ LT3 in hypothyroid subjects failed to find any differences in weight between combined LT4/LT3 and LT4 monotherapy (31)(32)(33)(34)(35)(36)(37)(38)(39). In addition, REE was not affected in the study by Celi et al (30).…”