Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well‐being and cognitive performance in hypothyroidism

Siegmund, Werner; Spieker, K; Weike, A. I.; Gießmann, Thomas; Modeß, Christiane; Dabers, Thomas; Kirsch, G.; Sänger, E.; Engel, George L.; Hamm, A; Nauck, Matthias; Wang, Meng

doi:10.1111/j.1365-2265.2004.02050.x

Cited by 142 publications

(126 citation statements)

References 23 publications

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“…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).…”

Section: Researches In Hypothyroidismsupporting

confidence: 62%

Psychosocial Factors in Patients with Thyroid Disease

Mandincová¹

2012

Thyroid and Parathyroid Diseases - New Insights Into Some Old and Some New Issues

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Section: Researches In Hypothyroidismsupporting

confidence: 62%

Psychosocial Factors in Patients with Thyroid Disease

Mandincová¹

2012

Thyroid and Parathyroid Diseases - New Insights Into Some Old and Some New Issues

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“…Several studies have recently reported that compared with levothyroxine alone, use of a combination of levothyroxine plus liothyronine produces no beneficial changes in cognitive performance in hypo-Effectiveness of thyroid supplement and tyrosine in Antarctica thyroid subjects (46)(47)(48). Other studies have reported moderate or no effects with T 4 supplementation (49,50).…”

Section: Discussionmentioning

confidence: 96%

Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged Antarctic residence

Palinkas

Reedy

Smith

et al. 2007

International Journal of Circumpolar Health

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Objectives. We previously reported that cognitive function improves with thyroxine and that there is a circannual pattern to mood and human TSH during Antarctic residence. To extend these findings, we examined the effects of tyrosine and a combined levothyroxine/ liothyronine supplement in euthyroid men and women who spent the austral summer (n=43) and/or winter (n=42) in Antarctica. Study Design. Randomized, placebo-controlled, clinical trial. Methods. Subjects were randomized to receive the following each day for 91.6±3.2 days in summer and/or 138.0± 3.2 days in winter: (1) 12g tyrosine mixed in 113g applesauce; (2) 50ug of levothyroxine and 12.5ug of liothyronine (T4-T3 Supplement); or (3) placebo. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric -Isolated and Confined Environments. Effectiveness of thyroid supplement and tyrosine in Antarctica Results. With placebo in summer, mood did not change while TSH decreased by 28%; in winter, there was a 136% degradation in mood (p<0.01) and TSH increased by 18%. With combined T4-T3 supplement, there was a 51% degradation in mood in summer compared with placebo (p<0.05) and TSH decreased by 57%; in winter there was a 135% degradation in mood while TSH was reduced by 26% (p<0.05). Tyrosine use in summer was associated with no change in mood and a 30% decline in TSH, while in winter there was a 47% improvement in mood and TSH decreased by 28% along with a 6% increase in fT3 (p<0.05). Conclusions. Administration of tyrosine leads to a significant reduction in serum TSH and improvement in mood in winter compared with placebo, while the combined T4-T3 supplement leads to a worsening of mood in summer and no improvement in winter. There appears to be a seasonal influence on the psychological response to interventions and the relationship to changes in TSH reductions. (Int J Circumpolar Health 2007; 66(5):401-417)

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“…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). Observations in crossover studies are not independent because the same patients receive both combination and monotherapy (1).…”

Section: Randomized Controlled Trials: a Reappraisalmentioning

confidence: 99%

“…It follows that the serum FT 4 -FT 3 ratio is higher in T 4 -replaced hypothyroid patients than in controls. Indeed, the serum FT 4 -FT 3 ratio in patients randomized to receive T 4 monotherapy in the meta-analysis ranges from 4.0 to 6.7 (7,8,10,11,13), higher than the value of 3.3 observed in controls (18). The serum FT 4 -FT 3 ratio during combination therapy ranged from 2.2 to 4.8; in only two of the RCTs, the ratios (3.3 and 3.4 respectively) were close to control values, but both studies still failed to demonstrate superiority of combination therapy over monotherapy (7,13).…”

Section: Randomized Controlled Trials: a Reappraisalmentioning

confidence: 99%

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

Wiersinga¹

2009

European Journal of Endocrinology

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Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over-or under-treatment with thyroxine (T 4 ) explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T 4 /tri-iodothyronine (T 3 ) combination therapy over T 4 monotherapy. However, each of these trials can be criticized, and none is perfect: most of them failed to mimic the physiological ratio of serum free T 4 (FT 4 ) to free T 3 (FT 3 ) concentrations. Development of a sustained-release T 3 preparation given as a single nighttime dose (together with levothyroxine once daily) might maintain physiological serum FT 4 -FT 3 ratio's throughout 24 h. Genetic polymorphisms in deiodinase 2 and thyroid hormone transporters have been associated with well-being, fatigue, depression, and greater improvement on combination therapy. Future trials should target carriers of these polymorphisms to see whether they do better on T 4 /T 3 combination therapy than on T 4 monotherapy. European Journal of Endocrinology 161 955-959

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Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well‐being and cognitive performance in hypothyroidism

Cited by 142 publications

References 23 publications

Psychosocial Factors in Patients with Thyroid Disease

Psychosocial Factors in Patients with Thyroid Disease

Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged Antarctic residence

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

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