Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, Ospedale di Circolo, 21100 Varese, Italy.
J Clin Endocrinol Metab. 2012 Dec;97(12):4454-63. doi: 10.1210/jc.2012-2389. Epub 2012 Oct 4.
Optimal doses of i.v. glucocorticoids for Graves' orbitopathy (GO) are undefined.
We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of i.v. methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit.
Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit.
The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.
静脉注射糖皮质激素治疗格雷夫斯眼病（GO）的最佳剂量尚未明确。
我们开展了一项多中心、随机、双盲试验，以确定三种剂量的静脉注射甲泼尼龙在 159 例中重度和活动性 GO 患者中的疗效和安全性。患者被随机分为 12 周内接受累积剂量 2.25、4.98 或 7.47g 的三组。在 12 周时，由盲法眼科医生进行客观评估，由盲法患者（使用 GO 特异性生活质量问卷）进行主观评估。每次就诊时记录不良事件。
总体而言，7.47g（52%）组的眼部改善更为常见，而 4.98g（35%；P=0.03）和 2.25g（28%；P=0.01）组较少见。与低剂量相比，高剂量方案导致眼运动的客观测量和临床活动评分的改善最大。所有组的临床活动评分均下降，而 2.25g 组下降最少。7.47g 组的生活质量改善最大，尽管未达到统计学意义。眼球突出度、睑裂、软组织变化和主观复视评分无显著差异。所有组均发生数例甲状腺毒性视神经病变。因此，在探索性的 24 周随访时，三组之间的差异不再明显。高剂量组不良事件略多，但低剂量组也有发生。在 12 周时眼病改善的患者中，7.47g 组的 33%、4.98g 组的 21%和 2.25g 组的 40%在探索性的 24 周随访时发生了复发性眼病。
7.47g 剂量在短期内优于低剂量。然而，这种益处是短暂的，且毒性略大。累积剂量 7.47g 的甲泼尼龙使用提供了短期优势，优于低剂量。这可能表明在大多数情况下使用中剂量方案，并将高剂量方案保留给最严重的 GO 病例。
