Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism

Xie, Junxia; Huang, Xia; Wang, Guo‐Ming; Wang, Yangang; Wang, Xufu; Zuo, Shi

doi:10.1097/mnm.0b013e32832c79e0

Cited by 83 publications

(21 citation statements)

References 33 publications

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“…the brain) level may be the responsible one for improvement of symptoms (24). In agreement with that, patients treated with combined levothyroxine and liothyronine (LT4 and LT3) therapy showed no improvement in wellbeing despite higher plasma levels of T3 compared with those treated with traditional T4 therapy (25, 26). Again, about 60% of circulating T3 is estimated to originate from the deiodinase 2 (D2) pathway in normal subjects (27).…”

Section: Discussionsupporting

confidence: 78%

Adding carbimazole to levothyroxine increases triiodothyronine and improves outcome in patients with primary hypothyroidism: a preliminary study from Egypt

et al. 2017

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BackgroundMany hypothyroid patients are not tolerant and not satisfied with levothyroxine (LT4). Older studies used large doses of both carbimazole and LT4 for Hashimoto’s thyroiditis (HT), because Graves’ disease (GD) and HT were considered as very closely related syndromes produced by thyroid autoimmunity.ObjectiveThe aim of the study was to determine the outcome after adding small doses of carbimazole to reduced doses of LT4 for patients with primary hypothyroidism, who are unable to tolerate LT4.MethodsThe study is a non-randomized, single arm, interventional study. It included 19 female patients diagnosed with primary hypothyroidism who could not tolerate LT4. Subjects were recruited from the outpatient clinic of AL-Azhar University Hospital in Damietta, Egypt from January to March 2015. They were divided into two groups; group 1 included 10 patients with HT and 2 patients with non-specified primary hypothyroidism, and group 2 included 7 patients with subtotal thyroidectomy for GD. All patients received carbimazole (10 mg/day) beside LT4 (25 μg thrice/week) for 10 weeks. Statistical analysis of the data was done by SPSS version 20, using paired-sample t-test, ANOVA, Chi square, and Pearson coefficient test.ResultsThere was significant increase in free triiodothyronine (FT3) in addition to significant improvement in depression and LT4 tolerance in the whole population. There was non-significant improvement in TSH in group 1 (p=0.053). Surprisingly, in group 2, in spite of significant increase in TSH (p=0.007) and non-significant decrease in free thyroxine (FT4), there was non-significant increase in FT3. Whether carbimazole improves the pathology of the hypothyroid gland or the peripheral deiodination of T4 to T3 (where the serum and tissue levels of the latter may be responsible for improvement of symptoms) is in need of investigation.ConclusionsAdding carbimazole to LT4 improves FT3, LT4 tolerance, and depression in primary hypothyroid female patients. Further studies are required to determine the appropriate doses of this regimen in different cases.Clinical trial registrationThis study was registered at Thai Clinical Trials Registration center (http://www.clinicaltrials.in.th) with registration ID: TCTR20170123003.FundingThe study received no fund or grant.

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Section: Discussionsupporting

confidence: 78%

Adding carbimazole to levothyroxine increases triiodothyronine and improves outcome in patients with primary hypothyroidism: a preliminary study from Egypt

et al. 2017

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“…The authors of the meta-analysis concluded: ‘It is doubtful whether further trials evaluating combination therapy are needed because the chances that the accumulated evidence will change are low’. A more recent systematic review in 2009 reached similar conclusions [35]. However, a recent RCT observed combination therapy was superior to monotherapy [5].…”

Section: Resultsmentioning

confidence: 55%

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

Wiersinga¹,

Duntas²,

Fadeyev³

et al. 2012

Eur Thyroid J

357

340

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Background: Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. Methods: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research. Conclusion: L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.

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“…The predominance of healthy middle-aged females in the current studies leads to potential problems with generalizing results to the entire hypothyroid population, including the elderly, males, and those with comorbidities. The heterogeneity of the trials makes it difficult to assess outcomes with the use of meta-analyses (38–40). …”

Section: Summary Of Combination Therapy Trialsmentioning

confidence: 99%

Persistent hypothyroid symptoms in a patient with a normal thyroid stimulating hormone level

Jonklaas

2017

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of Review A subset of patients being treated for hypothyroidism do not feel well taking levothyroxine replacement therapy, despite having a normal TSH. Pursuing a relative triiodothyronine deficiency as a potential explanation for patient dissatisfaction, has led to trials of combination therapy with liothyronine, with largely negative outcomes. This review attempts to reconcile these diverse findings, consider potential explanations, and identify areas for future research. Recent Findings Patients being treated with levothyroxine often have lower triiodothyronine levels than patients with endogenous thyroid function. Linking patient dissatisfaction with low triiodothyronine levels has fueled multiple combination therapy trials that have generally not shown improvement in patient quality of life, mood, or cognitive performance. Some trials, however, suggest patient preference for combination therapy. There continues, moreover, to be anecdotal evidence that patients have fewer unresolved symptoms while taking combination therapy. Summary The fourteen trials completed to date have suffered from employing doses of liothyronine that do not result in steady triiodothyronine levels, and having insufficient power to analyze results based on baseline dissatisfaction with therapy and patient genotype. Future trials that are able to incorporated such features may provide insight to what thyroid hormone preparations will most improve patient satisfaction with therapy.

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Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism

Cited by 83 publications

References 33 publications

Adding carbimazole to levothyroxine increases triiodothyronine and improves outcome in patients with primary hypothyroidism: a preliminary study from Egypt

Adding carbimazole to levothyroxine increases triiodothyronine and improves outcome in patients with primary hypothyroidism: a preliminary study from Egypt

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

Persistent hypothyroid symptoms in a patient with a normal thyroid stimulating hormone level

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