The relationship between lithium therapy and thyroid volume in smoking patients with bipolar disorder: a 3D computed tomography–based analysis

Lithium is a cornerstone treatment for bipolar disorder and has long been associated with thyroid abnormalities; however, evidence regarding its effects on thyroid morphology remains limited and is largely based on ultrasonography-derived estimates. This study aimed to evaluate the association between lithium therapy and thyroid volume using three-dimensional (3D) computed tomography (CT)-based volumetric analysis and to identify independent determinants of thyroid enlargement in smoking patients with bipolar disorder. In this retrospective cross-sectional study, 198 adult smokers were included: lithium-treated bipolar patients ( n = 64), bipolar patients not receiving lithium therapy ( n = 64), and healthy smoking controls ( n = 70). Thyroid volume was measured using semi-automated 3D segmentation on CT images. Inter-reader agreement was assessed using intraclass correlation coefficients and Bland–Altman analysis. Group comparisons were performed using analysis of variance with Tukey post hoc testing, and independent determinants of thyroid volume were evaluated using multiple linear regression analysis. Thyroid volume differed significantly among the study groups ( p = 0.005). Lithium-treated patients demonstrated significantly larger thyroid volumes than both non-lithium bipolar patients ( p = 0.037) and healthy controls ( p = 0.005), whereas no significant difference was observed between non-lithium bipolar patients and controls ( p = 0.812). Thyroid volume was not associated with serum lithium concentrations or treatment duration. In multivariable analysis, lithium use, male sex, thyroid nodules, and higher free triiodothyronine levels were independently associated with greater thyroid volume, while thyroid-stimulating hormone levels showed an inverse association. Goiter prevalence was significantly higher in lithium-treated patients (25.0%) than in non-lithium bipolar patients (9.4%) and controls (8.6%) ( p = 0.010). Volumetric measurements demonstrated excellent inter-reader reproducibility (ICC = 0.966). Lithium therapy was independently associated with increased thyroid volume in smoking patients with bipolar disorder, regardless of serum lithium levels or treatment duration. The absence of volumetric differences between lithium-naïve bipolar patients and healthy controls suggests that thyroid enlargement is primarily related to lithium exposure rather than bipolar disorder itself. Three-dimensional CT-based volumetry provides a highly reproducible and objective approach for quantifying lithium-associated thyroid morphological changes.