Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
N Engl J Med. 2011 May 19;364(20):1920-31. doi: 10.1056/NEJMoa1012985.
Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy.
We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score.
At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems.
Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).
氧自由基和细胞因子在格雷夫斯眼病中起致病作用。
我们进行了一项随机、双盲、安慰剂对照试验，以确定硒（抗氧化剂）或己酮可可碱（抗炎剂）在 159 例轻度格雷夫斯眼病患者中的疗效。患者口服硒（100μg，每日 2 次）、己酮可可碱（600mg，每日 2 次）或安慰剂（每日 2 次），治疗 6 个月后停药 6 个月。6 个月时的主要结局通过眼科医生进行的全面眼部评估（对治疗分配不知情）和患者完成的格雷夫斯眼病特定生活质量问卷进行评估。次要结局通过临床活动评分和复视评分进行评估。
在 6 个月评估时，与安慰剂相比，硒治疗而非己酮可可碱治疗与改善的生活质量（P<0.001）、更少的眼部受累（P=0.01）和格雷夫斯眼病的进展减缓（P=0.01）相关。所有组的临床活动评分均下降，但硒治疗组的变化更显著。12 个月的探索性评估证实了 6 个月时的结果。2 名安慰剂组和 1 名己酮可可碱组患者因病情恶化需要免疫抑制治疗。硒未出现不良反应，而己酮可可碱常引起胃肠道问题。
在轻度格雷夫斯眼病患者中，硒的应用显著改善了生活质量，减少了眼部受累，并减缓了疾病的进展。（由比萨大学和意大利教育、大学和研究部资助；EUGOGO 荷兰试验登记处编号，NTR524。）
