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Cited by 93Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism

Chao, Ma, Jiawei, Xie, Xia, Huang, Guoming, Wang, Yangang, Wang, Xufu, Wang, Shuyao, Zuo·2009·Nuclear Medicine Communications
DOI 10.1097/mnm.0b013e32832c79e0
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Abstract

Standard therapy for patients with hypothyroidism is replacement with synthetic thyroxine (T4). However, thyroxine plus triiodothyronine (T3) replacement therapy resulted in marked improvements in several items of the Profile of Mood States and in a few indices of psychometric function and quality of life. The adequacy of thyroxine alone versus thyroxine plus triiodothyronine to treat hypothyroidism has yielded conflicting results. Therefore, we conducted a systematic review of all included published, randomized controlled trials to evaluate the effects of thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism. We electronically searched Medline, Embase, the Cochrane Library, and China National Infrastructure. We also manually searched the Chinese Journal of Isotopes, Radiologia pratica, and the Chinese Journal of Endocrinology and Metabolism. A total of 10 randomized, double-blind trials (six crossovers, four parallel trials) were identified. Pooled analyses were suggestive of a statistically significant increase of free and total triiodothyronine, significant decrease of serum-free and total thyroxine in patients treated with thyroxine plus triiodothyronine, weighted mean difference (WMD) 0.03, -31.25, 2.19, 3.00; 95% confidence interval (CI) -0.14 to 0.20, -47.04 to -15.47, 0.46-3.92, 1.64-4.36, respectively. Thyroxin alone indicated significant benefits for psychological or physical well-being in terms of the General Health Questionnaire-28 (WMD: -2.90; 95% CI: -3.18 to -2.63), general health (WMD: -0.38; 95% CI: -0.71 to -0.05), physical component summary (WMD: 0.7; 95% CI: 0.53-0.87), and mental component summary (WMD: 0.58; 95% CI: 0.25-0.75); physical functioning (WMD: 1.60; 95% CI: 1.29-1.90), role-physical test (WMD: 3.60; 95% CI: 2.66-4.54), bodily pain (WMD: 2.50; 95% CI: 2.11-2.88), role-emotional (WMD: 2.08; 95% CI: 1.17-2.99), mental health (WMD: 1.30; 95% CI: 0.97-1.64) in items of the Short Form-36 Health Survey; general well-being in items of the Thyroid Symptom Questionnaire (WMD: -1.90; 95% CI: -2.48 to -1.32); better performance in the Letter Number Sequencing-working memory test in items of cognitive performance scores (WMD: 1.10; 95% CI: 0.08-2.13), significant treatment effect for blurred vision, aches, and pain (WMD: -4.66, -0.80; 95% CI: -5.339 to -4.00, -1.34 to -0.26, respectively). However, T4 plus T3 replacement improved cognitive performance (WMD: -0.49; 95% CI: -0.90 to -0.08). No significant statistical differences were found in biochemical variables, mood states clinical variables, adverse effects, and drop-out. In subgroup analysis, two included studies examined the relationship between mental improvement and causes of hypothyroidism, autoimmune, and nonautoimmune hypothyroidism, respectively. T4 alone suggested significantly higher total T4 (autoimmune and nonautoimmune thyroid, WMD: 4.5, 3.7; 95% CI: 2.24-6.76, 1.66-5.74, respectively), and significantly decreased thyroid-stimulating hormone (WMD: -0.05; 95% CI: -0.09 to -0.01). Statistically significant improvement occurred in pairs correctly recalled in the Digit Symbol Test for T4 plus T3 replacement (WMD: -1.60; 95% CI: -2.97 to -0.23) for nonautoimmune thyroid. In conclusion, on the basis of data from recent studies, we conclude that combined T4 and T3 treatment does not improve well-being, cognitive function, or quality of life compared with T4 alone. T4 alone may be beneficial in improving psychological or physical well-being. According to the current evidence, T4 alone replacement may remain the drug of choice for hypothyroid patients.

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  • Four systematic reviews and meta-analyses of these trials found no clear benefit of combination levothyroxine-liothyronine therapy over levothyroxine monotherapy in terms of mood, health-related quality of life, or cognitive function.

    “Furthermore, four systematic reviews and metaanalyses 12,13,180,181 of these trials found no clear benefit of combination levothyroxineliothyronine therapy over levothyroxine monotherapy in terms of mood, healthrelated quality of life, or cognitive function.”

    From Hypothyroidism (2024) · cites this paper as [181]

  • Four systematic reviews/meta-analyses of these trials found no clear benefit of combination liothyronine/levothyroxine replacement over levothyroxine monotherapy in terms of mood, health-related QoL or cognitive function.

    “four systematic reviews/meta -analyses 12,44 -46 of these trials found no clear benefit of combination liothyronine/levothyroxine replacement over levothyroxine monotherapy in terms of mood, health -related QoL or cognitive function.”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [46]

  • Trials do not show a benefit from thyroid hormone replacement in persistent subclinical hypothyroidism.

    “or to those with persistent subclinical hypothyroidism, where trials do not show a benefit from thyroid hormone replacement. 12,15,16,44 -46”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [46]

  • A more recent systematic review in 2009 reached similar conclusions to the 2006 meta-analysis.

    “A more recent systematic review in 2009 reached similar conclusions [35] .”

    From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [35]

  • Four systematic reviews and meta-analyses based on RCTs failed to show any advantages in quality of life, mood states, or psychometric performance for patients receiving combination therapy.

    “Four systematic reviews and meta-analyses based on RCTs failed to show any advantages in quality of life, mood states, or psychometric performance for patients receiving combination therapy (160–163).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [163]

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Authors
Chao, M., Jiawei, X., Xia, H., Guoming, W., Yangang, W., Xufu, W., & Shuyao, Z.
Affiliations
  • Stomatology Hospital (CN)
  • Qingdao University (CN)
Venue
Nuclear Medicine Communications
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-08
Volume
30
Issue
8
Pages
586-593
ISSN
0143-3636 (ISSN-L)
DOI
10.1097/mnm.0b013e32832c79e0
OpenAlex
W1490058975
Cited by
93
References
31
Citations by year
2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 9 · 2017: 3 · 2016: 15 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 9
FWCI
0.61
Type
journal article
Language
en
Open access
closed
Locations
  • Nuclear Medicine Communications (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
hypothyroidism, thyroxine, triiodothyronine, quality of life, mood, physical function, psychological well-being, thyroid hormone levels, GHQ-28, Profile of Mood States, physical component summary, mental component summary
MeSH terms
Animals, Humans, Hypothyroidism, Thyroxine, Triiodothyronine, Randomized Controlled Trials as Topic, Treatment Outcome, Hormone Replacement Therapy

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