HYPOTHYROIDISM IN PATIENTS TREATED WITH LITHIUM THERAPY: A SURVIVAL ANALYSIS
Keywords:
lithium, hypothyroidism, survival analysisAbstract
Objectives: To evaluate factors associated with time to onset of hypothyroidism among patients treated with lithium using survival analysis.
Material and Methods: This retrospective cohort study included 228 psychiatric patients who initiated lithium therapy for the first time at Somdet Chaopraya Institute of Psychiatry between 2018 and 2024. Demographic characteristics, treatment variables, and thyroid function test results were collected. Time to hypothyroidism was analyzed using Kaplan–Meier survival analysis, with group comparisons by log-rank test. Cox proportional hazards regression was used to evaluate the effects of sex, age at lithium initiation, valproate (VPA) use, and daily lithium dose. Sensitivity analysis was performed by additionally including physical illness to assess model robustness.
Results: Over a mean follow-up of 36.4 ± 27.3 months, 47 patients (20.6%) developed hypothyroidism. The Kaplan-Meier survival curve did not decline below 50% during follow-up; therefore, median survival time was not reached. Nonetheless, most events occurred within the first 1 - 3 years after lithium initiation. Female patients experienced significantly earlier onset than males (log-rank p = 0.023). Survival curves did not differ significantly across lithium dose categories. In multivariable Cox analysis, increasing age at lithium initiation was the only independent predictor of earlier hypothyroidism (adjusted HR 1.029 per year, p = 0.039). Inclusion of physical illness did not materially alter hazard ratio estimates (< 10%) and did not improve model explanatory value.
Conclusion: Older age at lithium initiation is independently associated with earlier onset of lithium-induced hypothyroidism. These findings support systematic, age-informed thyroid monitoring in psychiatric patients receiving lithium, particularly during the early phase of treatment.
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