Aim: Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with
normal free thyroxine (fT4). Vitamin D deficiency may contribute to thyroid dysfunction through immune
modulation and receptor activity in the thyroid gland. In Asian populations, where deficiency is highly
prevalent, empirical supplementation may be more feasible than routine testing. This study assessed the
effect of vitamin D replacement on TSH levels in treatment-naïve SCH patients. Methods: A randomized
controlled trial was conducted at the Endocrinology Department, FGPC Hospital, Islamabad. Eighty patients
aged 18–60 years with SCH (TSH 4.5–10 mIU/L, normal fT4) were randomized to receive either weekly
oral vitamin D₃ (50,000 IU) for 12 weeks or standard care. Baseline and follow-up assessments included
serum TSH, fT4, calcium, and phosphorus. Data were analyzed using SPSS v25; p<0.05 was considered
significant. Results: Baseline characteristics (age, gender, BMI, thyroid profile, vitamin D, Anti-TPO,
calcium) were comparable between groups (p>0.05). After 12 weeks, the vitamin D group showed a
significant reduction in TSH compared with placebo (4.34 ± 0.68 vs. 6.67 ± 0.98 mIU/L, p<0.001). Serum
25(OH) vitamin D increased markedly in the intervention group (38.41 ± 5.32 vs. 15.41 ± 3.57 ng/mL,
p<0.001). Free T4 and free T3 changes were minor and non-significant. Overall, 92.5% of vitamin D
recipients achieved TSH reduction versus 15% in placebo (p<0.001). ANCOVA confirmed a significant
treatment effect (F=152.207, p<0.001). Conclusion: Empirical vitamin D supplementation significantly
lowers TSH in treatment-naïve SCH patients, supporting its role as a practical therapeutic strategy in
populations with high deficiency prevalence.