Endocrine Abstracts

Objective: Vitamin D has potential immunomodulatory effects. We studied whether vitamin D3 supplementation affects the course of Graves’ disease (GD).

Methods: In a double-blind, placebo-controlled design, we randomized patients with a first time diagnosis of GD hyperthyroidism to daily supplementation with vitamin D3 70 mg (2800 IU) or placebo, as add-on to standard treatment with anti-thyroid drugs (ATD). The intervention was continued 12 months after cessation of ATD. Primary outcome was treatment failure (defined as either relapse of hyperthyroidism within 12 months after ATD cessation, failure to taper of ATD within 24 months of treatment, referral for radioiodine treatment or thyroidectomy). Secondary outcomes included the risk of relapse of hyperthyroidism after achieving euthyroidism and the influence of age, sex, smoking status, and vitamin D status. Data was analyzed using an intention-to-treat approach.

Results: A total of 278 patients were randomized. At baseline, participants were 44±1 years old, 79% were females, 35% had vitamin D insufficiency (<50 nmol/l), and 22% were smokers. The risk of treatment failure was 41% (95%CI, 33% to 50%) in the vitamin D group and 32% (95% CI, 24% to 40%) in the placebo group. This corresponded to a relative risk (RR) of 1.30 (95%CI: 0.95 to 1.78, P=0.10) with vitamin D supplementation. The relapse rates were also similar in the two groups (RR of relapse with vitamin D: 1.50 (95% CI, 0.92 to 2.44), P=0.10). Effects of the intervention showed a significant interaction with smoking status (P=0.01). In non-smokers, vitamin D supplementation showed an unfavorable effect on risk of treatment failure (odds ratio (OR) 2.03; 95%CI, 1.15 to 3.59, P=0.02) and relapse (OR 2.09; 95% CI: 1.04 to 4.18, P=0.04); no effect was found among smokers. The effect of intervention was not affected by age, sex, or vitamin D status.

Conclusion: In GD, the course of the disease is not improved with vitamin D supplementation. On the contrary, we observed trends for increased risk of treatment failure and relapse of hyperthyroidism with vitamin D supplementation. Given the enormous interest in immune-modulating benefits of vitamin D mainly based on association studies, our findings are important and raise concern of uncritical use of high-dose vitamin D supplementation in Graves’ disease.