Association of Serum 25-Hydroxyvitamin D and Vitamin D Receptor with Hyperthyroidism: A Case-Control Observational Study from South India.

Background: Hyperthyroidism is associated with metabolic, skeletal, and immunological disturbances, and growing evidence suggests that altered vitamin D signaling may contribute to thyroid dysfunction. However, data on serum 25-hydroxyvitamin D (25(OH)D) and vitamin D receptor (VDR) levels in hyperthyroidism from South India remain limited. Objectives: To evaluate the association of serum 25(OH)D and VDR levels with hyperthyroidism and to examine their relationship with thyroid function parameters and thyroid autoantibodies. Methods: This case-control study included 188 participants recruited from a tertiary care teaching hospital in South India between September 2022 and April 2024. The study comprised 80 patients with hyperthyroidism and 108 age- and sex-matched healthy controls. Serum thyroid hormones, thyroid autoantibodies, biochemical parameters, 25(OH)D, and VDR were measured using standardized laboratory methods. Comparisons between groups were made with appropriate parametric or non-parametric tests based on the nature of the data, while relationships between variables were examined using Pearson's correlation coefficient. A p-value below 0.05 was taken as statistically significant. Results: The mean age of cases and controls was 40.8 ± 12.6 and 39.9 ± 11.8 years, respectively. Females constituted 70.0% of cases and 70.4% of controls. Hyperthyroid patients had significantly lower BMI and significantly higher total and ionized calcium levels than controls. Thyroid hormone parameters showed marked derangement in cases, with significantly elevated T3, T4, FT3, and FT4 and suppressed TSH (all p<0.001). Serum 25(OH)D levels were significantly lower in cases than controls (18.6 ± 6.9 vs 28.9 ± 8.4 ng/mL, p<0.001), as were VDR levels (2.14 ± 0.76 vs 3.48 ± 0.91 ng/mL, p<0.001). Vitamin D deficiency was more prevalent among cases (62.5% vs 24.1%). Both 25(OH)D and VDR showed significant negative correlations with T3, T4, FT3, FT4, and thyroid autoantibodies, and weak positive correlations with TSH. Conclusions: Hyperthyroidism was significantly associated with lower serum 25(OH)D and VDR levels. Reduced vitamin D status and VDR concentrations were linked to greater thyroid hormonal excess and autoimmune activity, suggesting a potential role of vitamin D signaling in hyperthyroidism.