Combined T&lt;SUB&gt;4&lt;/SUB&gt; and T&lt;SUB&gt;3&lt;/SUB&gt; Therapy—Back to the Drawing Board

Cooper, David S.

doi:10.1001/jama.290.22.3002

Cited by 29 publications

(14 citation statements)

References 25 publications

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“…This would avoid the risks of supra-therapeutic T3 levels or substantial under-dosing, thus minimizing the duration of TSH stimulation and hypothyroid symptoms. Furthermore, the data reported in this manuscript could constitute the proof-of-concept for therapeutic substitution of l -T3 for l -T4 or combination TH therapy when a sustained-release l -T3 formulation becomes commercially available 19, 31.…”

Section: Discussionmentioning

confidence: 92%

“…13 These observations have led to the human experimentation of combination therapy with both L-T4 and L-T3 in the treatment of hypothyroidism. 14 Some studies indeed suggested marginal improvement of hypothyroid symptoms, [14][15][16][17][18] but the vast majority of the large trials do not support the need for, 19 or the superiority of the combination therapy. [20][21][22][23][24] Nonetheless, this modality remains a common practice among endocrinologists and general practitioners.…”

Section: Discussionmentioning

confidence: 99%

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The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients

Celi

Zemskova

Linderman

et al. 2010

Clinical Endocrinology

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Summary Context The substitution of liothyronine (l-T3) for levothyroxine (l-T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the l-T3 for l-T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of l-T3 and l-T4. Design Randomized, double-blind, cross-over intervention study. Setting NIH Clinical Center. Patients 10 thyroidectomized patients. Interventions Study participants were treated with l-T3 or l-T4 with a target TSH ≥0.5≤1.5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed-over according to the same scheme. Main outcome measures Area under the serum concentration-time curve of TSH from 0 to 60 minutes (AUC 0-60) and peak TSH serum concentration (Cmax) following thyrotropin-releasing hormone (TRH) stimulation test, total l-T4 and l-T3 dose (mcg/kg), and l-T4/l-T3 ratio. Results No difference was observed for time 0 TSH values between l-T3 and l-T4 replacement phases (1.48± 0.77 vs. 1.21± 0.62 mU/l, p=0.293) at average daily doses of 40.3±11.3 mcg lT-3 and 115.2±38.5 mcg lT-4, l-T3: l-T4 ratio 0.36±0.06. TRH stimulation test resulted in similar l-T3 vs.l-T4 TSH responses with AUC 0-60 of 326.1 (95% CI 232.6-457.1) and 247.1 (95% CI 153.8-397.1) mU*min /l (p=0.285); and Cmax of 6.83 (95% CI 4.88-9.55) and 5.23 (95% CI 3.31-8.3) mU/l (p=0.383). Conclusions This is the first study addressing the equivalency between l-T3 and l-T4 therapy measured by baseline and TRH-stimulated TSH. The therapeutic substitution of l-T3 for l-T4 was achieved at approximately 1:3 ratio.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients

Celi

Zemskova

Linderman

et al. 2010

Clinical Endocrinology

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“…Perhaps the truly ideal substitution therapy for hypothyroidism might be a combination of T4 and T3 in a carefully determined ratio and in a form in which the T3 is slowly absorbed in a time-released form [28]. Two editorials [24,29] recommended the use of T3 in a sustained release manner. The results of treatment with a combination of levothyroxine plus slow-release T3 leads to a considerable improvement of serum T4 and T3 values, the T4 : T3 ratio and serum TSH as compared with treatment with T4 only for hypothyroid patients.…”

Section: Discussionmentioning

confidence: 99%

Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism

Xie¹,

Huang²,

Wang³

et al. 2009

Nuclear Medicine Communications

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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...

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“…It is inexpensive and it stabilizes thyroid hormone levels. There is no reason to use T 3 , and there is no evidence of benefit from combined T 3 and T 4 therapy (351,352). Small doses, i.e., 25-75 g/d, are often adequate to normalize serum TSH levels in SHypo.…”

Section: N Treatment Of Subclinical Hypothyroidismmentioning

confidence: 99%

The Clinical Significance of Subclinical Thyroid Dysfunction

2007

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Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.

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Combined T<SUB>4</SUB> and T<SUB>3</SUB> Therapy—Back to the Drawing Board

Cited by 29 publications

References 25 publications

The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients

The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients

Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism

The Clinical Significance of Subclinical Thyroid Dysfunction

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