Effect of vitamin D supplementation on Graves' disease: The DAGMAR trial.

Objective Treatment options in Graves' disease are limited, do not target the underlying autoimmunity, and relapse rates following a course of anti-thyroid drug reach 50%. Previous research has shown promising results for a role for vitamin D in Graves' disease. We aimed to investigate whether vitamin D reduces failure to enter and sustain remission in patients with Graves' disease treated with anti-thyroid drug. Design A multicenter, double-blinded, randomized, placebo-controlled trial comparing Vitamin D 70 mcg once daily (2800 IU) or placebo. The intervention was given first as add-on to anti-thyroid drug treatment, maximally 24 months, and then for 12 months after anti-thyroid drug cessation. Inclusion 2015 to 2017 and study completion December 2020. Patients included were adults with a first-time diagnosis of Graves' disease treated with anti-thyroid drug. Exclusion criteria included pregnancy and glucocorticoid treatment. The primary endpoint was failure to enter and sustain remission defined as relapse of hyperthyroidism within 12 months after anti-thyroid drug cessation, inability to stop anti-thyroid drug within 24 months, or radioiodine treatment or thyroidectomy. Two-hundred-seventy-eight patients were included, four withdrew consent. No adverse effects. Results Participants were 44±14 years at enrollment and 79% were female. The risk of failure to enter and sustain remission was 42% (95% confidence interval [CI], 33% to 50%) in the vitamin D group and 32% (24% to 40%) in the placebo group corresponding to a relative risk (RR) of 1.30 (95% CI, 0.95 to 1.78). Conclusions Vitamin D supplementation did not improve the treatment of Graves' disease in patients with a normal or insufficient vitamin D status. Thus, supplementation with high-dose vitamin D cannot be recommended for Graves' disease.