Akirov Amit, Fazelzad Rouhi, Ezzat Shereen, Thabane Lehana, Sawka Anna M
Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Institute of Endocrinology, Beilinson Hospital, Petach Tikva, Israel.
Front Endocrinol (Lausanne). 2019 Jul 24;10:477. doi: 10.3389/fendo.2019.00477. eCollection 2019.
The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered. We performed a systematic review and meta-analysis of blinded randomized controlled trials (RCTs), reporting how often hypothyroid patients prefer combination L-T3/L-T4 treatment to L-T4 alone. We also explored for explanatory factors for combination therapy preference in sensitivity analyses examining trial, patient, and disease characteristics. Potential dose-response relationships were explored using meta-regression analyses. We searched 9 electronic databases (from inception until February, 2019), supplemented with a hand-search. Two reviewers independently screened abstracts and citations and reviewed full-text papers, with consensus achieved on the included studies. Two reviewers independently critically appraised the quality of included studies and abstracted the data. Random effects meta-analyses were reported for the percentage of patients preferring combination L-T3/T-T4 therapy over L-T4 alone. A binomial distribution of choices (i.e., preference of combination therapy or no preference for combination therapy) was assumed. We included 7 blinded RCTs including 348 hypothyroid individuals in the primary meta-analysis. The pooled prevalence rate for preference of combination therapy over L-T4 was 46.2% (95% confidence interval 40.2%, 52.4%) ( = 0.231 for the difference from chance). There was no significant statistical heterogeneity among study results (Q = 7.32, degrees of freedom = 6, = 0.293, = 18.0%). In sensitivity analyses, combination treatment preference was explained in part by treatment effects on TSH concentration, mood and symptoms, but not quality of life nor body weight. In a secondary dose-response meta-regression analyses, a statistically significant association of treatment preference was identified for total daily L-T3 dose, but not L-T3:L-T4 dose ratio. In conclusion, in RCTs in which patients and investigators were blinded to treatment allocation, approximately half of participants reported preferring combination L-T3 and L-T4 therapy compared to L-T4 alone; this finding was not distinguishable from chance. An observed potential positive L-T3 dose effect on treatment preference deserves further study, with careful consideration of thyroid biochemical indices and patient reported outcomes.
甲状腺功能减退症管理的标准治疗方法是使用左甲状腺素（L-T4）进行治疗。有时患者对L-T4不满意，会考虑将左三碘甲状腺原氨酸（L-T3）与L-T4联合使用。我们对双盲随机对照试验（RCT）进行了系统评价和荟萃分析，报告甲状腺功能减退症患者选择L-T3/L-T4联合治疗而非单独使用L-T4治疗的频率。我们还在敏感性分析中探讨了联合治疗偏好的解释因素，分析了试验、患者和疾病特征。使用荟萃回归分析探索潜在的剂量反应关系。我们检索了9个电子数据库（从创建至2019年2月），并辅以手工检索。两名审阅者独立筛选摘要和引文并审阅全文论文，就纳入的研究达成共识。两名审阅者独立严格评估纳入研究的质量并提取数据。报告了随机效应荟萃分析中选择L-T3/T-T4联合治疗而非单独使用L-T4治疗的患者百分比。假设选择的二项分布（即联合治疗偏好或无联合治疗偏好）。在主要荟萃分析中，我们纳入了7项双盲RCT，包括348名甲状腺功能减退症患者。联合治疗优于L-T4的汇总患病率为46.2%（95%置信区间40.2%，52.4%）（与预期差异的P = 0.231）。研究结果之间无显著统计学异质性（Q = 7.32，自由度 = 6，P = 0.293，I² = 18.0%）。在敏感性分析中，联合治疗偏好部分由对促甲状腺激素（TSH）浓度、情绪和症状的治疗效果解释，但与生活质量或体重无关。在二次剂量反应荟萃回归分析中，确定了每日L-T3总剂量与治疗偏好之间存在统计学显著关联，但L-T3:L-T4剂量比与治疗偏好无关。总之，在患者和研究者对治疗分配不知情的RCT中，约一半参与者报告相较于单独使用L-T4，更喜欢L-T3和L-T4联合治疗；这一发现与预期无差异。观察到的L-T3剂量对治疗偏好的潜在积极影响值得进一步研究，同时要仔细考虑甲状腺生化指标和患者报告的结果。
