Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue, Symptoms of Depression, and Working Memory Versus Treatment With Levothyroxine Alone

Rodriguez, Tom; Lavis, Victor R.; Meininger, Janet C.; Kapadia, Asha S.; Stafford, L

doi:10.4158/ep.11.4.223

Cited by 72 publications

(76 citation statements)

References 16 publications

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“…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).…”

Section: Lt4 Therapy Energy Expenditure and Body Compositionmentioning

confidence: 72%

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

Samuels

Kolobova

Smeraglio

et al. 2016

Thyroid

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Background: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. Methods: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. Results: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group ( p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups ( p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition. Conclusions: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

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Section: Lt4 Therapy Energy Expenditure and Body Compositionmentioning

confidence: 72%

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

Samuels

Kolobova

Smeraglio

et al. 2016

Thyroid

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“…Most patients included in the present study had a high baseline psychological morbidity. But subset analyses of previous trials do not support this explanation (6,7,12,14), although there may be a sample size problem. Could it be something else?…”

Section: Randomized Controlled Trials: a Reappraisalmentioning

confidence: 85%

“…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%

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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“…Most studies have assessed changes in mood, cognition function and QoL during combination therapy with LT4/LT3 (11,12,21,(23)(24)(25)(26)28,(30)(31)(32)40,41). Two meta-analyses including 10 (14) and 11 (13) of these studies showed no improvement in bodily pain, well-being, mood, fatigue, QoL or cognition.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a meta-analysis evaluating 11 randomized controlled trials with a total of 1,216 patients concluded that there is no evidence supporting the superiority of LT4/LT3 combination therapy regarding improvements in bodily pain, mood, fatigue, QoL, cognition, body weight or blood lipids (13). Not even patients with depression (11), high dissatisfaction with LT4 therapy (23), psychiatric symptoms (24), or fatigue (25) benefited from the combination therapy.…”

Section: Discussionmentioning

confidence: 99%

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

Kaminski

Miasaki

Paz-Filho

et al. 2016

Arch. Endocrinol. Metab.

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Objective: To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods: This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results: Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/ LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions: The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms. Arch Endocrinol Metab. 2016;60(6):562-72

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Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue, Symptoms of Depression, and Working Memory Versus Treatment With Levothyroxine Alone

Abstract: Background-This study was planned at a time when important questions were being raised about the adequacy of using one hormone to treat hypothyroidism instead of two.

Cited by 72 publications

References 16 publications

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

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

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

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

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