Response to: Oral lithium as an adjunctive therapy during radioiodine treatment for hyperthyroidism

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We thank Hammond and colleagues for their interest in our communication pertaining to oral lithium as an adjunctive therapy during radioiodine treatment (RAI) for hyperthyroidism 1 and would also like to congratulate the authors for their published studies on the same subject 2,3. Consequent to the treatment with adjuvant lithium, the investigators reported 22.4% increase in cure rate (78.4 vs. 56%), which is the primary endpoint for these studies. We believe that two areas where some differences exist in the literature and would need a critical evaluation in the future studies from clinical practice viewpoint: (a) dose, duration, and scheduling of lithium carbonate with respect to RAI and (b) outcome of the primary endpoint and advantage of RAI–lithium regimen compared with conventional RAI.
Dose, duration, and scheduling of lithium carbonate with respect to RAI: In our letter communication 1, we had discussed some variations in timing and dose scheduling of lithium among various studies, with the majority starting lithium 3–5 days before RAI. The study by Hammond et al. 2 belonged to the other group where lithium carbonate (800 mg) was started on the day of RAI. Thus, the regimen in this study had similarity with that of Bal et al. 4 and Lingudu et al.5. With regard to the duration of treatment, the study by Hammond et al. 3 and Lingudu et al. 5 advocated a shorter duration (7 and 6 days, respectively) compared with that of Bal and colleagues (3 weeks). However, the studies by Płazińska et al. 6 and Chouhan et al. 7 advocated a protocol to start lithium 6 and 3 days before RAI until 3 and 5 days post-RAI therapy. With a view to reducing any probable side effects of lithium, the regimen should be just adequate to produce the desired results, though we believe that initiating the lithium priming few days before the therapy would be rational, and could better the outcome of cure rates.
Outcome of the primary endpoint and advantage of RAI–lithium regimen compared with conventional RAI: The primary objectives of RAI–lithium regimen are enhancing intrathyroidal 131I (in one controlled study, lithium carbonate 885 mg daily for 2 weeks with RAI increased radiation dose by 40%) and consequently fewer incidences of treatment failure and probably reduction in the requirement of RAI activity to achieve cure. In this respect, the authors’ study results are noteworthy, as it documented substantially superior (additional 22.4%) and earlier cure rates with RAI–lithium regimen. The literature is dichotomous with respect to the efficacy of the combined regimen; similar cure rates were documented by Bal et al. 4, whereas enhanced cure rates (additional 20%) were reported by Lingudu et al. 5 similar to that obtained by Hammond et al. 3, whereas Płazińska et al. 6 reported better results in the first year and similar in the second and third years compared with the conventional RAI group.
Ancillary advantages of lithium priming and secondary endpoints: Irrespective of the aforementioned differences with regard to the primary outcome results and regimen adopted, there are certain common points of agreement regarding ancillary advantages of the RAI–lithium regimen; in addition to enhancing RAI retention, lithium priming decreases serum thyroid hormone concentrations (both by inhibiting coupling of iodotyrosine residues and release of T4 and T3), which could prove clinically beneficial. In our study, we found reduced serum FT4 level across all subtypes of toxic goiter with significance in the diffuse toxic group. Other investigators have also obtained similar results; the study by Bogazzi et al.

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