Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N, Denmark.
Department of Internal Medicine, Herlev Hospital, Herlev, Hovedstaden, Denmark.
Thyroid. 2023 Sep;33(9):1110-1118. doi: 10.1089/thy.2023.0111. Epub 2023 Jun 26.
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. 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. 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]. 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. ClinicalTrials.gov NCT02384668.
治疗 Graves 病（GD）的选择有限，且不能针对潜在的自身免疫，抗甲状腺药物（ATD）治疗后复发率达到 50%。先前的研究表明维生素 D 在 GD 中具有一定作用。我们旨在研究维生素 D 是否可降低 GD 患者接受 ATD 治疗后缓解失败和持续缓解率。一项多中心、双盲、随机安慰剂对照试验，比较了每日一次 70 mcg 维生素 D（2800 IU）或安慰剂。干预措施最初作为 ATD 治疗的附加治疗，最长 24 个月，然后在 ATD 停药后 12 个月进行。纳入期为 2015 年至 2017 年，研究完成于 2020 年 12 月。纳入的患者为首次接受 ATD 治疗的 GD 成人患者。排除标准包括妊娠和糖皮质激素治疗。主要终点是缓解失败和持续缓解，定义为 ATD 停药后 12 个月内发生甲状腺功能亢进症复发、24 个月内无法停止 ATD 治疗、放射性碘治疗或甲状腺切除术。该研究纳入了 278 例患者，其中 4 例患者撤回了同意。未发现不良反应。入组时，参与者年龄为 44±14 岁，79%为女性。维生素 D 组缓解失败和持续缓解的风险为 42%[95%置信区间（CI）33-50%]，安慰剂组为 32%[CI 24-40%]，相应的相对风险为 1.30[CI 0.95-1.78]。维生素 D 补充剂并不能改善维生素 D 状态正常或不足的 GD 患者的治疗效果。因此，不推荐 GD 患者补充大剂量维生素 D。ClinicalTrials.gov NCT02384668。
