Determining the best dose of lithium carbonate as adjuvant therapy to radioactive iodine for the treatment of hyperthyroidism: a systematic review and meta-analysis

Abstract

Background: Hyperthyroidism poses challenges, and common treatments like Radioactive Iodine (RAI) have limitations, prompting exploration of adjunctive approaches. This meta-analysis evaluates the combined impact of RAI and Lithium carbonate (LiCO3) on cure rates and thyroid hormone levels.

Methods: We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science for studies comparing LiCO3 combined with RAI to RAI alone. Pooled results analyzed cure rates and Free T3/T4 changes. A subgroup analysis was conducted based on LiCO3 dosage and treatment duration, while meta-regression was performed to assess covariates such as the patient's age, RAI dose, and lithium dose. The risk of bias was evaluated using ROB2, ROBINS-1, and NOS, while the statistical analyses were conducted using Revman software 5.4.1.

Results: Analysis of 14 studies involving 2047 patients revealed a significantly increased cure rate with RAI and LiCO3 compared to RAI alone (RR 1.12, 95% CI [1.03,1.23], p = 0.01). Subgroup analysis revealed higher cure rates with short-duration intensified doses of LiCO3, while short-duration diluted doses reduced cure rates. No significant differences were noted in euthyroid and hypothyroid states. Changes in free T3 showed no significant difference between the arms at 7 days and the most common time point. A significant decrease in free T4 favored RAI with LiCO3 at 7 days (MD -4.90, 95% CI [-7.91, -1.89], p = 0.001), and the most common time point (MD -3.83, 95% CI [-7.45, -0.20], p = 0.04). Meta-regression analysis indicated better cure rates in older patients (p < 0.001) and lower total lithium doses (p < 0.001).

Conclusion: Treatment with RAI combined with LiCO3 significantly enhanced cure rates, particularly when using short-duration intensified doses of LiCO3. Additionally, LiCO3 effectively reduced T4 levels without altering T3 levels. Future research is needed to validate our findings.

Clinical trial number: Not applicable.

Keywords: Adjuvant therapy; Hyperthyroidism; Lithium carbonate; Meta-analysis; Radioactive iodine.

Fig. 1

PRISMA flow diagram for included studies

Fig. 2

Forest plot comparing RAI + LICO3 versus RAI alone: (A) Cure rate (B) Euthyroid state and (C) Hypothyroid state

Fig. 3

Forest plot illustrating the subgroup analysis of cure rates based on LiCO3 doses and duration, comparing RAI plus LiCO3 to RAI alone

Fig. 4

Forest plot comparing RAI + LICO3 versus RAI alone: (A) Change in freeT3 at 7 days and (B) Change in freeT4 at 7 days

Fig. 5

The funnel plot for the cure rate outcome.: (A) before the subgroup analysis and (B) after the subgroup analysis