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Article Abstract
Context: Although some patients with hypothyroidism prefer combination therapy with Liothyronine (LT3) and Levothyroxine (LT4), the safety of LT3 remains unresolved.
Objective: We undertook a multi-source systematic-review and meta-analysis of LT3 safety.
Data Sources: We searched PubMed for articles relating to death, adverse events (AEs), and cardiovascular outcomes in LT3 users. We also searched AEs data in the UK yellow-card scheme and US Food and Drug Administration Adverse Reporting System (FAERS).
Data Extraction: Data was extracted independently by two reviewers. Out of 1814 articles identified, 52 studies were selected, comprising 21 randomised controlled trials (RCTs), 4 cohort-studies, and 27 case-reports. Meta-analyses were conducted for adverse outcomes in RCTs and cohort studies of combination vs. monotherapy.
Data Synthesis: LT3-related AEs were only reported with unregulated LT3 use or pharmacy compounding errors. LT3 and LT4 showed similar adverse severity profiles in the yellow-card scheme. Disproportionality analysis in FAERS database showed no increased LT3 safety signals. Meta-analysis of RCTs (n=2128) showed similar AEs risk for combination vs. monotherapy (Relative risk [RR] 1.22, 95% Confidence Interval [95%CI] 0.66-2.25). Cohort study meta-analysis (LT3 vs. LT4-only users, n=630,254) showed no increased risk of atrial fibrillation (RR 1.10 95%CI, 0.74-1.63), heart failure (RR 1.54, 95%CI 0.95-2.47), or strokes (RR 0.86, 95%CI 0.11-6.75), but reduced mortality risk was observed for LT3 (RR 0.70, 95%CI 0.62-0.78).
Conclusions: Our findings are reassuring that regulated LT3 use is not associated with risk of death or serious adverse outcomes. More studies are needed to supplement existing data.
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| http://dx.doi.org/10.1210/clinem/dgaf449 | DOI Listing |
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