Effect of Vitamin D Supplementation on Graves' Disease: The DAGMAR Trial.

Objective: Treatment options in Graves' disease (GD) are limited and do not target the underlying autoimmunity, and relapse rates following a course of antithyroid drug (ATD) reach 50%. Previous research has shown promising results for a role of vitamin D in GD. We aimed to investigate whether vitamin D reduces failure to enter and sustain remission in patients with GD treated with ATD. 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 ATD treatment, maximally 24 months, and then for 12 months after ATD cessation. Inclusion period was from 2015 to 2017 and study completion by December 2020. Patients included were adults with a first-time diagnosis of GD treated with ATD. 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 ATD cessation, inability to stop ATD within 24 months, or radioiodine treatment or thyroidectomy. Two hundred seventy-eight patients were included in the study, and 4 patients withdrew consent. No adverse effects were found. Results: Participants were aged 44 ± 14 years at enrollment and 79% were female. The risk of failure to enter and sustain remission was 42% [95% confidence interval (CI) 33-50%] in the vitamin D group and 32% [CI 24-40%] in the placebo group corresponding to a relative risk of 1.30 [CI 0.95-1.78]. Conclusions: Vitamin D supplementation did not improve the treatment of GD in patients with normal or insufficient vitamin D status. Thus, supplementation with high-dose vitamin D cannot be recommended for GD. Study registration: ClinicalTrials.gov NCT02384668.

Muscle Performance and Postural Stability Are Reduced in Patients with Newly Diagnosed Graves' Disease.

Background: Reduced muscle strength is an acknowledged symptom of Graves' disease, but the knowledge on severity is sparse. This study aimed to investigate muscle strength, balance, and muscle function in patients with Graves' disease compared to age- and sex-matched healthy controls. Methods: Using a cross-sectional design, 55 patients newly diagnosed with Graves' disease were compared to 55 euthyroid controls, matched on sex, age, and menopausal status. Isometric muscle strength (N) and maximum force production (N/s) were measured across different muscles groups using a dynamometer chair and postural stability (balance) in different positions using a stadiometer. Muscle function was assessed using the Timed-Up-and-Go test and the Repeated Chair Stand test. Results: Patients and controls were well matched. Handgrip maximum muscle strength as well as strength at elbow and knee flexion and extension were significantly impaired in patients compared to controls. Maximum force production was only significantly reduced at elbow flexion. Patients performed the Timed-Up-and-Go and the Repeated Chair Stand test significantly slower than controls, and postural stability was significantly reduced in patients compared to controls in all positions. Free triiodothyronine correlated with reduced muscle strength and postural stability. Conclusions: At the time of diagnosis, Graves' disease is associated with impaired maximum muscle strength, performance, and balance, whereas maximum force production is overall comparable to euthyroid controls.