MON-447 - Comparative Effectiveness of Liquid versus Tablet Levothyroxine in Congenital Hypothyroidism: A Systematic Review and Meta-analysis

Background &

Aims: Congenital hypothyroidism requires prompt and effective levothyroxine therapy to achieve adequate hormonal control and prevent long-term complications. While tablet formulations remain the standard treatment, liquid levothyroxine has been increasingly used in clinical practice. However, whether these formulations provide equivalent control of thyroid function in patients with congenital hypothyroidism remains uncertain. We aimed to compare the effectiveness of liquid versus tablet levothyroxine in this population.

Methods: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials and observational studies comparing liquid and tablet levothyroxine in congenital hypothyroidism. The primary outcomes were thyroid-stimulating hormone (TSH) levels, free thyroxine (fT4) levels, and the proportion of patients achieving normal T4. Secondary outcomes included subgroup analyses according to follow-up duration. Random-effects models (REML) were used to estimate pooled effects as relative risks (RR) or mean differences (MD) with 95% confidence intervals. Analyses were stratified by follow-up duration, and heterogeneity was assessed using the I² statistic.

Results: No significant differences were observed between liquid and tablet levothyroxine in the proportion of patients achieving normal T4 levels across all timepoints, including early (15 days, 1 and 3 months) and long-term follow-up (6 to 36 months), with pooled estimates consistently close to null and low-to-moderate heterogeneity. Similarly, pooled analysis of fT4 levels demonstrated no meaningful differences between formulations at any timepoint. For TSH, the overall pooled estimate showed no statistically significant difference between formulations; however, subgroup analysis revealed a transient reduction in TSH levels at 6 months favoring the liquid formulation (MD −1.3, 95% CI −2.1 to −0.6), which was not sustained in longer follow-up periods. No significant subgroup interactions were identified across timepoints.

Conclusion: Liquid and tablet levothyroxine provide comparable biochemical control in patients with congenital hypothyroidism. Although liquid formulations may be associated with transient differences in TSH levels during follow-up, these effects are not sustained over time and do not translate into consistent long-term advantages. These findings suggest that treatment outcomes are primarily driven by appropriate dosing and monitoring rather than formulation choice. Further studies evaluating clinically relevant outcomes, including growth and neurodevelopment, are needed to better inform treatment decisions.

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