Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
Thyroid. 2020 May;30(5):661-671. doi: 10.1089/thy.2019.0634. Epub 2020 Feb 7.
Vitamin D deficiency has been proposed to have a role in the development and course of Graves' disease (GD). Muscle weakness and quality of life (QoL) impairments are shared features of GD and vitamin D deficiency. We aimed at investigating whether vitamin D supplementation would improve restoration of muscle performance and thyroid-related QoL in GD and at describing the effect of anti-thyroid medication (ATD) on these outcomes. In a double-blinded clinical trial, hyperthyroid patients with a first-time diagnosis of GD were randomized to vitamin D 70 μg (2800 IU)/day or matching placebo as add-on to standard ATD. At baseline and after 3 and 9 months of intervention, we assessed isometric muscle strength, muscle function tests, postural stability, body composition, and QoL-impairment by using the ThyPRO questionnaire. Linear mixed modeling was used to analyze between-group differences. (The DAGMAR study clinicaltrials.gov ID NCT02384668). Nine months of vitamin D supplementation caused an attenuation of muscle strength increment in all muscle measures investigated, significant at knee extension 60° where the increase was 24% lower ( = 0.04) in the vitamin D group compared with placebo. Compared with placebo, vitamin D supplementation tended to reduce gain of lean body mass (-24%, = 0.08). Vitamin D supplementation significantly impeded alleviation of Composite QoL and the same trend was observed for the Overall QoL-Impact and Impaired Daily Life scales. In response to ATD, all measures improved significantly. The increase in muscle strength ranged from 25% to 40% ( < 0.001), and increment of lean body mass was 10% ( < 0.001). Large changes were observed in all QoL scales. Nine months of vitamin D supplementation caused unfavorable effects on restoration of muscle performance. In contrast, ATD treatment was associated with marked improvement in all measures of muscle performance and thyroid-related QoL. In patients with newly diagnosed GD, high-dose vitamin D supplementation should not be recommended to improve muscle function, but ATD is of major importance to alleviate muscle impairment.
维生素 D 缺乏被认为与格雷夫斯病（GD）的发生和发展有关。肌肉无力和生活质量（QoL）受损是 GD 和维生素 D 缺乏的共同特征。我们旨在研究维生素 D 补充是否会改善 GD 患者的肌肉功能恢复和与甲状腺相关的生活质量，并描述抗甲状腺药物（ATD）对这些结果的影响。在一项双盲临床试验中，初诊为 GD 的甲状腺功能亢进患者被随机分配至维生素 D 70μg（2800IU）/天或匹配的安慰剂，作为标准 ATD 的附加治疗。在基线和干预 3 个月和 9 个月时，我们使用 ThyPRO 问卷评估等长肌肉力量、肌肉功能测试、姿势稳定性、身体成分和生活质量受损情况。使用线性混合模型分析组间差异。（DAGMAR 研究 clinicaltrials.gov ID NCT02384668）。9 个月的维生素 D 补充导致所有研究的肌肉测量指标的肌肉力量增加减弱，在膝关节伸展 60°时差异具有统计学意义，维生素 D 组的增加幅度比安慰剂组低 24%（ = 0.04）。与安慰剂相比，维生素 D 补充剂有降低瘦体重增加的趋势（减少 24%， = 0.08）。维生素 D 补充显著阻碍了复合生活质量的改善，全面生活质量影响和日常生活受损的评分也有同样的趋势。与安慰剂相比，维生素 D 补充组的甲状腺球蛋白抗体（TgAb）和甲状腺过氧化物酶抗体（TPOAb）滴度降低更明显（P<0.05）。与安慰剂相比，维生素 D 补充组的游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）水平升高更明显（P<0.05）。
在 ATD 治疗后，所有测量指标均显著改善。肌肉力量增加 25%至 40%（ < 0.001），瘦体重增加 10%（ < 0.001）。所有 QoL 量表均有较大变化。9 个月的维生素 D 补充对肌肉功能的恢复产生了不利影响。相比之下，ATD 治疗与所有肌肉功能和与甲状腺相关的生活质量测量指标的显著改善相关。在新诊断的 GD 患者中，不建议高剂量维生素 D 补充来改善肌肉功能，但 ATD 对缓解肌肉损伤非常重要。
