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Meta-Analysis
. 2025 Feb 18;110(3):887-900.
doi: 10.1210/clinem/dgae651.

Treatment Preferences in Patients With Hypothyroidism

Fabyan Esberard de Lima Beltrão  1   2 , Giulia Carvalhal  3 , Daniele Carvalhal de Almeida Beltrão  2   4 , Fabricia Elizabeth de Lima Beltrão  1   2 , Miriam O Ribeiro  5 , Matthew D Ettleson  6 , Helton Estrela Ramos  7   8   9 , Antonio C Bianco  6
Affiliations
Meta-Analysis

Treatment Preferences in Patients With Hypothyroidism

Fabyan Esberard de Lima Beltrão et al. J Clin Endocrinol Metab. .

Abstract

Context: Levothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE).

Objective: This work aimed to assess patient preferences in the treatment of hypothyroidism.

Methods: A systematic review, meta-analysis, meta-regression, and network meta-analysis of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs L-T4 + L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by 4 researchers.

Results: Eleven RCTs (8 cross-over studies) with a total of 1135 patients were considered. Overall, 24% of patients preferred L-T4 vs 52% who preferred L-T4 + L-T3 or DTE; 24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (relative risk [RR]: 2.20; 95% CI, 1.38-3.52; P = .0009). Excluding 4 studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97; 95% CI, 1.52-2.54; P < .00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84; 95% CI, 1.50-5.39; P < .00001). Network meta-analysis confirmed the preference for DTE and L-T3 + L-T4 vs L-T4 alone.

Conclusion: Patients with hypothyroidism prefer combination therapy (L-T3 + L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism.

Keywords: DTE; L-T3; L-T4; combination therapy; hypothyroidism; patient preference.

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Figures

Figure 1.
Figure 1.
PRISMA flowchart depicting literature search and screening process (n indicates number of studies).
Figure 2.
Figure 2.
Risk-of-bias assessment using the Cochrane Risk of Bias tool (RoB V.2.0).
Figure 3.
Figure 3.
Forest plot of patient preferences (combination therapy vs monotherapy) across all 11 selected studies.
Figure 4.
Figure 4.
Funnel plots of patient preferences (combination therapy vs monotherapy) across all 11 selected studies.
Figure 5.
Figure 5.
Forest plot depicting patient preferences (combination therapy vs monotherapy) following the exclusion of four studies (26-28, 30) after funnel plot analysis.
Figure 6.
Figure 6.
Forest plot of patient preferences (combination therapy vs monotherapy and combination therapy vs no preference) across crossover trials.
Figure 7.
Figure 7.
Funnel plots of patient preferences across crossover trial: A (combination therapy vs monotherapy) and B (combination therapy vs no preference).
Figure 8.
Figure 8.
Forest plot of patient preferences (combination therapy vs monotherapy and combination therapy vs no preference) across crossover trials following the exclusion of 3 studies (26, 27, 30) after funnel plot analysis.
Figure 9.
Figure 9.
Pie chart depicting patients' preferences at the end of the crossover study periods: A) including all crossover studies and B) after the exclusion of three studies (26, 27, 30), following funnel plot analysis.
Figure 10.
Figure 10.
Power analysis of patient preferences (combination therapy vs monotherapy) across all 11 selected studies.
Figure 11.
Figure 11.
Network meta-analysis (Forest plot [random-effects model]) results of patient preferences for monotherapy (L-T4) vs combination therapy (L-T3 + L-T4) vs DTE: A, Across all selected studies (11 studies) and B, across crossover trials (8 studies); forest plot of the efficacy outcomes.
Figure 12.
Figure 12.
Schematic of the treatments used in the network meta-analysis (monotherapy [L-T4] vs combination therapy [L-T3 + L-T4] vs DTE): A, Across all 11 selected studies and B, across crossover trials (8 studies); geometry of the treatment network. The nodes in the graph layout correspond to the treatments, and the edges display the observed treatment comparisons. The thickness of the edges is proportional to the number of participants in trials, directly comparing the 3 connected treatments.
See this image and copyright information in PMC

References

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