SAT-397 - Liquid or Soft-Gel Levothyroxine Versus Tablet Levothyroxine in Athyreotic Adults after Total Thyroidectomy: A Systematic Review and Meta-Analysis

Background: Achieving stable thyroid hormone replacement after total thyroidectomy is challenging owing to the variability in levothyroxine (LT4) absorption. Newer liquid and soft-gel formulations may offer improved bioavailability compared to conventional tablets, but their benefits in thyroidectomized patients remain uncertain.

Objective: To compare the effectiveness of liquid and soft-gel LT4 with tablet LT4 in athyreotic adults following total thyroidectomy.

Methods: A systematic review and meta-analysis were conducted according to the PRISMA 2020 guidelines. The MEDLINE, Embase, CENTRAL, and Scopus databases were searched from inception to January 1, 2026. Randomized controlled trials and cohort studies enrolling adults after total thyroidectomy were included. The primary outcome was serum thyroid-stimulating hormone (TSH) level. Secondary outcomes included circulating T4 and T3 levels. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a random effects model. Subgroup analyses were performed based on the disease etiology, malabsorption status, and study design.

Results: Nine studies comprising 1,115 participants were included. Liquid or soft-gel LT4 was associated with significantly lower TSH compared with tablets (SMD −0.91; 95% CI −1.52 to −0.30; p=0.003), with high heterogeneity (I²=95%). Subgroup analysis showed a significant effect in patients treated for benign disease but not in those with differentiated thyroid cancer. A significant benefit was observed in patients without documented malabsorption, whereas no statistically significant difference was found in those with malabsorption. Liquid LT4 resulted in higher T4 (SMD 0.34; 95% CI 0.15–0.52) and T3 levels (SMD 0.25; 95% CI 0.06–0.44), with no heterogeneity.

Conclusion: Liquid or soft-gel LT4 provides improved biochemical control compared to tablets in selected thyroidectomized patients, particularly those treated for benign disease or with unstable TSH on tablets. Routine substitution for all patients was not supported, highlighting the need for individualized LT4 therapy.

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