RIT is a first-line treatment strategy for Graves’ disease, especially in patients with ATD failure, allergies, combined liver injury, leukopenia/deficiency, or disease recurrence. Uptake efficiency and EHL in the thyroid are the key factors affecting the 131I efficacy in treating Graves’ disease. Increasing the dosage of radioactive iodine could improve the cure rate, but at the same time, the patient's radiation exposure is also likely to be increased accordingly. Theoretically, extending the EHL enhances the effectiveness of 131I therapy for hyperthyroidism. Several studies demonstrated that short-term pretreatment with lithium carbonate could prolong the EHL and result in superior cure rates with lower 131I doses[17]. Nevertheless, other reports indicated that lithium carbonate had little effect on the efficacy of 131I treatment[18]. Owing to the controversial and insufficient study results, the treatment strategy of 131I pretreatment with lithium carbonate is not widely used in clinical practice[6, 7, 19, 20]. Therefore, more detailed data are needed to elucidate the effectiveness and predictive factors of lithium carbonate pretreatment. In the present study, we found that lithium carbonate pretreatments increased the EHL in 65.33% (147/225) patients, and 61.22% (90/147) have an extended EHL for more than 0.5 days. These data further demonstrated the significance of lithium carbonate as an adjunct for RIT. More importantly, we further analyzed the underlying clinical factors which could predict the EHL trend after lithium carbonate pretreatment in patients with hyperthyroidism. The results indicated that younger age (< 40.5 years), female gender, TRAb positive, TgAb positive, lower blood concentration of TPOAb (< 279.5 IU/mL), and shorter baseline EHL (< 4.85 days) were predictive factors for post-EHL prolongation after lithium carbonate treatment. These results indicate a critical role of lithium carbonate for RIT in hyperthyroidism, and suggest the significance of these predictive factors in this treatment strategy, simultaneously providing a basis for rational administration of lithium carbonate, which has not been reported previously.
Previous study suggested that lithium carbonate could increase iodine retention in thyroid, but the influence of lithium carbonate on iodine uptake is not well studied. Kumar reported a significant increase in the thyroid counts in lithium treated rats after 131I administration at 4 h and 24 h, when compared to control group[21]. In the present study, the data suggested that lithium carbonate treatment had little effect on the RAIUs at 2 h and 4 h, while RAIU measured at 24 h was increased significantly. It is reported that 24 h RAIU is an independent predictor of 131I treatment efficiency, and high 24 h RAIU is associated with better treatment outcomes. Therefore, lithium carbonate is likely to increase post-EHL by increasing RAIU at 24 h, while longer EHL has been shown to be associated with higher RIT efficacy[22].
Positivity for TPOAb is common in patients with Graves’ disease. It is reported that TPOAb is an independent predictor of long-term remission after ATD treatment[23]. However, the correlation between TPOAb positivity and the effectiveness of 131I treatment is still largely unknown. Our present study revealed that the EHL was prolonged in patients with low titer TPOAb after a 7-day lithium carbonate treatment, and previous studies have confirmed that prolonged EHL is a predictive factor for the effectiveness of radioactive iodine[22]. The relationship between lithium carbonate and TPOAb may provide innovative therapeutic approach for these patients.
It is also reported that elder patients or patients with TRAb and/or TgAb positivity are also predictive factors for lower possibility of one-time cure by RIT[22]. Nevertheless, according to the results of our current study, positive TRAb and/or TgAb can also predict an increase in EHL after lithium carbonate treatment. Based on the above results, it is speculated that TRAb and/or TgAb positive patients benefit from increased EHL after lithium carbonate treatment, which may be beneficial for improving the success rate of radioactive iodine therapy. Of course, these intriguing possibilities need to be verified in the future.
In conclusion, we assessed the impact of lithium carbonate pretreatment on 131I EHL and analysed the related predictive factors in patients with hyperthyroidism. Additionally, young female with TRAb positive, TgAb positive, low blood titer of TPOAb, and/or short pre-EHL is more likely to achieve longer ΔEHL after a short-term lithium carbonate administration. These results may provide theoretical support and a useful adjuvant treatment option for patients with hyperthyroidism preparing for RIT. As a result, further prospective studies of larger samples, multi-center and long-term detailed follow-up data are needed in the future.